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Fixed-dose combo pill for PAH promises accelerated benefit: A DUE
Already commonly used in combination for the treatment of pulmonary arterial hypertension (PAH), macitentan and tadalafil are safe and effective in a fixed-dose combination even as first-line therapy, according to a randomized multicenter comparative trial.
The fixed-dose combination “led to a highly significant and marked improvement in pulmonary vascular resistance when compared to macitentan and tadalafil as monotherapies,” Kelly Chin, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Guidelines encourage rapid PVR reductions
In practice, it is common to start treatment with either the endothelial receptor antagonist (ERA) macitentan, the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, or other frequently used medications for PAH, and to then add additional treatments, according to Dr. Chin. She pointed out, however, that guidelines, including those issued jointly by the European Society of Cardiology and the European Respiratory Society, encourage rapid escalation of therapy to quickly lower pulmonary vascular resistance (PVR).
In general, both macitentan and tadalafil are well tolerated, but the advantage and the safety of rapidly reducing PVR when these are initiated together in a single pill had not been evaluated previously in a major trial. In this double-blind phase III trial, called A DUE, 187 patients in functional class II or III PAH were randomized. The three-arm study included both treatment naive patients and patients who had been on stable doses (> 3 months) of an ERA or a PDE5 inhibitor, explained Dr. Chin, director of pulmonary hypertension at the UT Southwestern, Dallas.
Treatment naive patients, representing about 53% of the study population, were randomized to 10 mg macitentan monotherapy, 40 mg tadalafil monotherapy, or a fixed-dose, single-pill combination containing both. If on a stable dose of an ERA at trial entry, patients were randomized to 10 macitentan as a monotherapy or to the fixed dose combination. Patients entering the trial already on a stable dose of a PDE5 inhibitor were randomized to 40 mg tadalafil or the combination.
PVR reduced twofold on combination therapy
Relative to macitentan monotherapy, the percentage change from baseline in PVR by ratio of geometric mean, which was the primary outcome, was about twice as high on the combination (45% vs. 23%) at the end of the 16-week trial. This translates into a 29% PVR reduction (hazard ratio, 0.71; P < .0001).
For combination therapy relative to tadalafil monotherapy, the advantage for the fixed dose combination (44% vs. 22%) was about the same, also providing a nearly 30% relative reduction (HR, 0.72; P < .0001).
The increases in 6-minute walk distance (6MWD) at 16 weeks, a secondary endpoint, numerically favored the combination pill over both macitentan monotherapy (52.9 vs. 39.5 meters; P = .38) and tadalafil (43.4 vs. 15.9 meters; P = .059), but only the improvement relative to tadalafil monotherapy was considered a trend.
The proportion of patients who experienced at least one serious adverse event was higher in the combination arm (14.0%) relative to single agent macitentan (8.6%) or single agent tadalafil (9.1%). The adverse events and serious adverse events more common on the combination included hypotension, fluid retention, and anemia. This latter side effect occurred in 18.7%, 2.9%, and 2.3% in the combination, macitentan monotherapy, and tadalafil arms, respectively.
Several of those invited by the ACC to discuss the paper, including Lee R. Goldberg, MD, section chief of advanced heart failure and cardiac transplant, University of Pennsylvania, Philadelphia, raised concern about the increased rate of anemia among those in the combination pill. Two of the patients (2%) treated with the combination developed a hemoglobin < 8 g/dL.
Overall, nine (8.4%) of those on the fixed-dose combination, two (4.5%) of those randomized to tadalafil monotherapy, and none of the patients randomized to macitentan discontinued therapy due to side effects.
Anemia risk unexpected
Based on “the unexpected signal of an anemia risk,” Biykem Bozkurt, MD, PhD, chair of cardiology at Baylor College of Medicine, Houston, said that a larger scale trial with a longer follow-up is needed. While the concept of front-loading two drugs is attractive “for the very challenging PAH population,” she called for further evaluation of this safety signal before clinicians switch from the current practice of starting with one PAH therapy before adding others.
In addition, Dr. Bozkurt said a more definitive study would be helpful in determining whether starting with a fixed-pill combination is better than sequential treatment to improve quality of life. Dr. Bozkurt said it is likely that the lack of significant benefit on 6MWD in this study was due to the relatively small sample size, but an improvement in this measure would be another reason to consider a front-line fixed-dose combination.
Dr. Chin, in an interview, did not agree. She agreed that a larger sample size might have yielded a significant improvement in 6MWD, but she noted this outcome was moving in the right direction and was not the primary endpoint. In her opinion, this phase 3 trial does confirm that fixed-dose combination is well tolerated, has acceptable safety, and markedly improves PVR, fulfilling the guideline goal of controlling PAH more quickly.
Dr. Chin reports financial relationships with Altavant, Arena, Gossamer Bio, Janssen, Merck, ShouTi, and United Therapeutics. Dr. Goldberg reports financial relationships with Abbott, Respicardia/Zoll, and Viscardia. Dr. Bozkurt reports financial relationships with Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Cardurion, LivaNova, Relypsa, Renovacor, Sanofi-Aventis, and Vifor.
Already commonly used in combination for the treatment of pulmonary arterial hypertension (PAH), macitentan and tadalafil are safe and effective in a fixed-dose combination even as first-line therapy, according to a randomized multicenter comparative trial.
The fixed-dose combination “led to a highly significant and marked improvement in pulmonary vascular resistance when compared to macitentan and tadalafil as monotherapies,” Kelly Chin, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Guidelines encourage rapid PVR reductions
In practice, it is common to start treatment with either the endothelial receptor antagonist (ERA) macitentan, the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, or other frequently used medications for PAH, and to then add additional treatments, according to Dr. Chin. She pointed out, however, that guidelines, including those issued jointly by the European Society of Cardiology and the European Respiratory Society, encourage rapid escalation of therapy to quickly lower pulmonary vascular resistance (PVR).
In general, both macitentan and tadalafil are well tolerated, but the advantage and the safety of rapidly reducing PVR when these are initiated together in a single pill had not been evaluated previously in a major trial. In this double-blind phase III trial, called A DUE, 187 patients in functional class II or III PAH were randomized. The three-arm study included both treatment naive patients and patients who had been on stable doses (> 3 months) of an ERA or a PDE5 inhibitor, explained Dr. Chin, director of pulmonary hypertension at the UT Southwestern, Dallas.
Treatment naive patients, representing about 53% of the study population, were randomized to 10 mg macitentan monotherapy, 40 mg tadalafil monotherapy, or a fixed-dose, single-pill combination containing both. If on a stable dose of an ERA at trial entry, patients were randomized to 10 macitentan as a monotherapy or to the fixed dose combination. Patients entering the trial already on a stable dose of a PDE5 inhibitor were randomized to 40 mg tadalafil or the combination.
PVR reduced twofold on combination therapy
Relative to macitentan monotherapy, the percentage change from baseline in PVR by ratio of geometric mean, which was the primary outcome, was about twice as high on the combination (45% vs. 23%) at the end of the 16-week trial. This translates into a 29% PVR reduction (hazard ratio, 0.71; P < .0001).
For combination therapy relative to tadalafil monotherapy, the advantage for the fixed dose combination (44% vs. 22%) was about the same, also providing a nearly 30% relative reduction (HR, 0.72; P < .0001).
The increases in 6-minute walk distance (6MWD) at 16 weeks, a secondary endpoint, numerically favored the combination pill over both macitentan monotherapy (52.9 vs. 39.5 meters; P = .38) and tadalafil (43.4 vs. 15.9 meters; P = .059), but only the improvement relative to tadalafil monotherapy was considered a trend.
The proportion of patients who experienced at least one serious adverse event was higher in the combination arm (14.0%) relative to single agent macitentan (8.6%) or single agent tadalafil (9.1%). The adverse events and serious adverse events more common on the combination included hypotension, fluid retention, and anemia. This latter side effect occurred in 18.7%, 2.9%, and 2.3% in the combination, macitentan monotherapy, and tadalafil arms, respectively.
Several of those invited by the ACC to discuss the paper, including Lee R. Goldberg, MD, section chief of advanced heart failure and cardiac transplant, University of Pennsylvania, Philadelphia, raised concern about the increased rate of anemia among those in the combination pill. Two of the patients (2%) treated with the combination developed a hemoglobin < 8 g/dL.
Overall, nine (8.4%) of those on the fixed-dose combination, two (4.5%) of those randomized to tadalafil monotherapy, and none of the patients randomized to macitentan discontinued therapy due to side effects.
Anemia risk unexpected
Based on “the unexpected signal of an anemia risk,” Biykem Bozkurt, MD, PhD, chair of cardiology at Baylor College of Medicine, Houston, said that a larger scale trial with a longer follow-up is needed. While the concept of front-loading two drugs is attractive “for the very challenging PAH population,” she called for further evaluation of this safety signal before clinicians switch from the current practice of starting with one PAH therapy before adding others.
In addition, Dr. Bozkurt said a more definitive study would be helpful in determining whether starting with a fixed-pill combination is better than sequential treatment to improve quality of life. Dr. Bozkurt said it is likely that the lack of significant benefit on 6MWD in this study was due to the relatively small sample size, but an improvement in this measure would be another reason to consider a front-line fixed-dose combination.
Dr. Chin, in an interview, did not agree. She agreed that a larger sample size might have yielded a significant improvement in 6MWD, but she noted this outcome was moving in the right direction and was not the primary endpoint. In her opinion, this phase 3 trial does confirm that fixed-dose combination is well tolerated, has acceptable safety, and markedly improves PVR, fulfilling the guideline goal of controlling PAH more quickly.
Dr. Chin reports financial relationships with Altavant, Arena, Gossamer Bio, Janssen, Merck, ShouTi, and United Therapeutics. Dr. Goldberg reports financial relationships with Abbott, Respicardia/Zoll, and Viscardia. Dr. Bozkurt reports financial relationships with Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Cardurion, LivaNova, Relypsa, Renovacor, Sanofi-Aventis, and Vifor.
Already commonly used in combination for the treatment of pulmonary arterial hypertension (PAH), macitentan and tadalafil are safe and effective in a fixed-dose combination even as first-line therapy, according to a randomized multicenter comparative trial.
The fixed-dose combination “led to a highly significant and marked improvement in pulmonary vascular resistance when compared to macitentan and tadalafil as monotherapies,” Kelly Chin, MD, reported at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
Guidelines encourage rapid PVR reductions
In practice, it is common to start treatment with either the endothelial receptor antagonist (ERA) macitentan, the phosphodiesterase-5 (PDE-5) inhibitor tadalafil, or other frequently used medications for PAH, and to then add additional treatments, according to Dr. Chin. She pointed out, however, that guidelines, including those issued jointly by the European Society of Cardiology and the European Respiratory Society, encourage rapid escalation of therapy to quickly lower pulmonary vascular resistance (PVR).
In general, both macitentan and tadalafil are well tolerated, but the advantage and the safety of rapidly reducing PVR when these are initiated together in a single pill had not been evaluated previously in a major trial. In this double-blind phase III trial, called A DUE, 187 patients in functional class II or III PAH were randomized. The three-arm study included both treatment naive patients and patients who had been on stable doses (> 3 months) of an ERA or a PDE5 inhibitor, explained Dr. Chin, director of pulmonary hypertension at the UT Southwestern, Dallas.
Treatment naive patients, representing about 53% of the study population, were randomized to 10 mg macitentan monotherapy, 40 mg tadalafil monotherapy, or a fixed-dose, single-pill combination containing both. If on a stable dose of an ERA at trial entry, patients were randomized to 10 macitentan as a monotherapy or to the fixed dose combination. Patients entering the trial already on a stable dose of a PDE5 inhibitor were randomized to 40 mg tadalafil or the combination.
PVR reduced twofold on combination therapy
Relative to macitentan monotherapy, the percentage change from baseline in PVR by ratio of geometric mean, which was the primary outcome, was about twice as high on the combination (45% vs. 23%) at the end of the 16-week trial. This translates into a 29% PVR reduction (hazard ratio, 0.71; P < .0001).
For combination therapy relative to tadalafil monotherapy, the advantage for the fixed dose combination (44% vs. 22%) was about the same, also providing a nearly 30% relative reduction (HR, 0.72; P < .0001).
The increases in 6-minute walk distance (6MWD) at 16 weeks, a secondary endpoint, numerically favored the combination pill over both macitentan monotherapy (52.9 vs. 39.5 meters; P = .38) and tadalafil (43.4 vs. 15.9 meters; P = .059), but only the improvement relative to tadalafil monotherapy was considered a trend.
The proportion of patients who experienced at least one serious adverse event was higher in the combination arm (14.0%) relative to single agent macitentan (8.6%) or single agent tadalafil (9.1%). The adverse events and serious adverse events more common on the combination included hypotension, fluid retention, and anemia. This latter side effect occurred in 18.7%, 2.9%, and 2.3% in the combination, macitentan monotherapy, and tadalafil arms, respectively.
Several of those invited by the ACC to discuss the paper, including Lee R. Goldberg, MD, section chief of advanced heart failure and cardiac transplant, University of Pennsylvania, Philadelphia, raised concern about the increased rate of anemia among those in the combination pill. Two of the patients (2%) treated with the combination developed a hemoglobin < 8 g/dL.
Overall, nine (8.4%) of those on the fixed-dose combination, two (4.5%) of those randomized to tadalafil monotherapy, and none of the patients randomized to macitentan discontinued therapy due to side effects.
Anemia risk unexpected
Based on “the unexpected signal of an anemia risk,” Biykem Bozkurt, MD, PhD, chair of cardiology at Baylor College of Medicine, Houston, said that a larger scale trial with a longer follow-up is needed. While the concept of front-loading two drugs is attractive “for the very challenging PAH population,” she called for further evaluation of this safety signal before clinicians switch from the current practice of starting with one PAH therapy before adding others.
In addition, Dr. Bozkurt said a more definitive study would be helpful in determining whether starting with a fixed-pill combination is better than sequential treatment to improve quality of life. Dr. Bozkurt said it is likely that the lack of significant benefit on 6MWD in this study was due to the relatively small sample size, but an improvement in this measure would be another reason to consider a front-line fixed-dose combination.
Dr. Chin, in an interview, did not agree. She agreed that a larger sample size might have yielded a significant improvement in 6MWD, but she noted this outcome was moving in the right direction and was not the primary endpoint. In her opinion, this phase 3 trial does confirm that fixed-dose combination is well tolerated, has acceptable safety, and markedly improves PVR, fulfilling the guideline goal of controlling PAH more quickly.
Dr. Chin reports financial relationships with Altavant, Arena, Gossamer Bio, Janssen, Merck, ShouTi, and United Therapeutics. Dr. Goldberg reports financial relationships with Abbott, Respicardia/Zoll, and Viscardia. Dr. Bozkurt reports financial relationships with Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Cardurion, LivaNova, Relypsa, Renovacor, Sanofi-Aventis, and Vifor.
AT ACC 2023
Depressive symptoms tied to higher stroke risk, worse outcomes
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Encouraging 3-year data for TAVR in low-risk patients: EVOLUT
Three-year results from the Evolut trial seem to provide more reassurance on the use of transcatheter aortic valve replacement (TAVR) in low-surgical-risk patients.
The 3-year results show that low-surgical-risk patients undergoing aortic valve replacement continue to show lower rates of all-cause mortality and disabling stroke with TAVR, compared with surgery.
The rates of all-cause mortality or disabling stroke (the primary endpoint) at 3 years were 7.4% with TAVR and 10.4% with surgery.
Rates of new pacemaker implantation continued to be higher after TAVR and the frequency of new onset atrial fibrillation was more common after surgery.
“At 3 years, the rate of all-cause mortality or disabling stroke after TAVR with the Evolut valve compared very favorably to surgery. The absolute difference between treatment arms remained consistent with a 30% relative reduction in the hazard of death or disabling stroke, with a P value that just missed statistical significance,” said Evolut investigator John Forrest, MD, Yale University School of Medicine, New Haven, Conn.
“The Kaplan-Meier curves show what we’ve come to expect – an early separation of the curves – but what’s unique here, and seen for the first time, is that the early separation is maintained at year 1 and year 2, and between years 2 and 3 the curve didn’t start to come together, but, if anything, separated a little,” Dr. Forrest commented.
“Both components of the primary endpoint – all cause mortality and disabling stroke – numerically favor TAVR. The separation of the curves for stroke are maintained, and if anything, we see a further slight separation of the curves as we go forward out to 3 years in terms of all-cause mortality,” he added.
Dr. Forrest presented the 3-year results from the Evolut trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. They were simultaneously published online in the Journal of the American College of Cardiology.
Dr. Forrest also reported that TAVR patients continued to have better valve hemodynamics at 3 years and very low rates of valve thrombosis; moreover, rates of moderate or greater paravalvular regurgitation and paravalvular leak (factors that can affect valve durability) were also low, although mild paravalvular regurgitation was higher with TAVR.
“In these low-risk patients, the durability of the valve is going to be critically important,” Dr. Forrest commented. “The excellent valve performance and durable outcomes out to 3 years in low-risk patients affirms the role of TAVR in this population,” he concluded.
On how these results may affect clinical practice, Dr. Forrest said: “I think in the U.S. these results reaffirm what we are doing. It gives us confidence to continue treating low-risk patients and being comfortable with that.”
He added: “Outside the U.S., the guidelines are a little different. Maybe we should reconsider some of these guidelines based on these data.”
David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., who is not involved in the TAVR studies, said: “The results provide a little more reassurance ... that will go a little way further.”
“Uncertainty remains regarding long-term durability of the transcatheter valve in low-risk patients who are generally younger and likely more active than higher-risk cohorts,” he added. “The current 3-year results provide more confidence as the outcome curves for death and disabling stroke are trending in the right direction for TAVR versus surgery.”
Dr. Moliterno pointed out that while rates of paravalvular regurgitation and permanent pacemaker placement are decreasing with newer generation Evolut devices and implantation techniques, he noted that according to the U.S. Social Security Administration, patients aged 74 years as enrolled in this low-risk cohort have an additional life expectancy of approximately 12 years. “So, we have more device durability (and coronary access feasibility) to prove.”
In his presentation, Dr. Forrest explained that TAVR is now approved in the United States for all patients with aortic stenosis regardless of surgical risk and has become the dominant form of aortic valve replacement. Current ACC/AHA guidelines recommend that heart teams utilize a shared decision-making process when discussing aortic valve replacement with patients aged 65-80 years. In younger, lower-risk patients, the faster recovery and short-term benefits after TAVR must be balanced with long-term durability; however, only limited intermediate and long-term data exist to guide such discussions in this patient population.
The Evolut Low Risk trial randomly assigned 1,414 patients in need of aortic valve replacement to TAVR with a self-expanding, supra-annular valve or surgery. Results at 1 and 2 years have shown a similar benefit in the primary endpoint of all-cause mortality/disabling stroke for the less invasive TAVR procedure.
The current 3-year results suggest the benefit appears to be maintained out for another year.
The main results show that the rate of death or disabling stroke was 7.4% in the TAVR group versus 10.4% in the surgery group, giving a hazard ratio of 0.70 (P = .051).
In the JACC paper, the authors report that the absolute difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: –1.8% at year 1; –2.0% at year 2; and –2.9% at year 3.
Other key results on valve durability show that mild paravalvular regurgitation was increased in the TAVR group (20.3%) versus 2.5% with surgery. However, rates of moderate or greater paravalvular regurgitation for both groups were below 1% and not significantly different between groups.
Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1 mm Hg TAVR vs. 12.1 mm Hg surgery; P < .001) at 3 years.
However, pacemaker placement was much higher in the TAVR group (23.2%), compared with 9.1% in the surgery group.
On the other hand, the surgery group had a greater incidence of atrial fibrillation (40%) versus 13% with TAVR.
Quality-of-life results looked good in both groups.
“As we’ve come to expect, patients recover more quickly after TAVR, so at 30 days their quality of life is better than those who have undergone surgery,” Dr. Forrest commented. “But by 1 year, both groups are doing exceptionally well and, remarkably, here by 3 years both groups have greater than a 20-point increase in their KCCQ score, showing a very large improvement in quality of life.”
Discussant of these latest results at the ACC late-breaking trials session, James Hermiller, MD, St. Vincent Ascension Heart Center, Indianapolis, said: “This 3-year data continues to demonstrate that the gift of TAVR keeps giving.”
Noting that the divergence in the effect curves was primarily driven by mortality rather than stroke, he asked whether this was cardiac or noncardiac mortality that was reduced.
Dr. Forrest responded: “It was a fairly equal contribution – a little bit more cardiac death. We have to remember that although the average age in this study was 74, there were some patients over 80 who were still low-surgical-risk included so we are going to see noncardiac death as well.”
Dr. Hermiller drew attention to the high pacemaker rate in the TAVR group and asked how these patients fared in comparison to those who didn’t need a pacemaker.
Dr. Forrest replied: “I think it’s fair to say that putting in a pacemaker is not a benign procedure. Patients who got a pacemaker did slightly worse than those who didn’t get a pacemaker, so we need to try to drive that rate down.”
He added that the number of patients needing a pacemaker after TAVR has come down with new implantation techniques and new generation valves.
“We realize that using a cusp overlap technique can significantly reduce the need for a pacemaker, and we see from registry data that with the use of this new technique the need for a pacemaker has dropped down to 8%-9%, significantly less than seen in this study,” Dr. Forrest commented.
Dr. Hermiller also asked about how TAVR affects future access for catheterization or percutaneous coronary intervention.
Dr. Forrest noted that 24 patients in the TAVR group required PCI in first 3 years, and all the PCI procedures had been successful. He noted that operators reported the procedure to be easy or moderately easy in about 75%-80% of cases and difficult in about 20% of patients. “So, it is slightly more challenging to engage the coronaries and have to go through the frame, but it is very feasible.”
Dr. Forrest concluded that: “These results provide patients and heart teams important data to aid in the shared decision-making process.”
But he acknowledged that longer term data are still needed. “And the potential impact that hemodynamics, valve design, new pacemakers, and other secondary endpoints have on long-term outcomes will be important to follow in this group of low-risk patients.”
The Evolut Low Risk trial was funded by Medtronic. Dr. Forrest has received grant support/research contracts and consultant fees/honoraria/speakers bureau fees from Edwards Lifesciences and Medtronic.
A version of this article first appeared on Medscape.com.
Three-year results from the Evolut trial seem to provide more reassurance on the use of transcatheter aortic valve replacement (TAVR) in low-surgical-risk patients.
The 3-year results show that low-surgical-risk patients undergoing aortic valve replacement continue to show lower rates of all-cause mortality and disabling stroke with TAVR, compared with surgery.
The rates of all-cause mortality or disabling stroke (the primary endpoint) at 3 years were 7.4% with TAVR and 10.4% with surgery.
Rates of new pacemaker implantation continued to be higher after TAVR and the frequency of new onset atrial fibrillation was more common after surgery.
“At 3 years, the rate of all-cause mortality or disabling stroke after TAVR with the Evolut valve compared very favorably to surgery. The absolute difference between treatment arms remained consistent with a 30% relative reduction in the hazard of death or disabling stroke, with a P value that just missed statistical significance,” said Evolut investigator John Forrest, MD, Yale University School of Medicine, New Haven, Conn.
“The Kaplan-Meier curves show what we’ve come to expect – an early separation of the curves – but what’s unique here, and seen for the first time, is that the early separation is maintained at year 1 and year 2, and between years 2 and 3 the curve didn’t start to come together, but, if anything, separated a little,” Dr. Forrest commented.
“Both components of the primary endpoint – all cause mortality and disabling stroke – numerically favor TAVR. The separation of the curves for stroke are maintained, and if anything, we see a further slight separation of the curves as we go forward out to 3 years in terms of all-cause mortality,” he added.
Dr. Forrest presented the 3-year results from the Evolut trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. They were simultaneously published online in the Journal of the American College of Cardiology.
Dr. Forrest also reported that TAVR patients continued to have better valve hemodynamics at 3 years and very low rates of valve thrombosis; moreover, rates of moderate or greater paravalvular regurgitation and paravalvular leak (factors that can affect valve durability) were also low, although mild paravalvular regurgitation was higher with TAVR.
“In these low-risk patients, the durability of the valve is going to be critically important,” Dr. Forrest commented. “The excellent valve performance and durable outcomes out to 3 years in low-risk patients affirms the role of TAVR in this population,” he concluded.
On how these results may affect clinical practice, Dr. Forrest said: “I think in the U.S. these results reaffirm what we are doing. It gives us confidence to continue treating low-risk patients and being comfortable with that.”
He added: “Outside the U.S., the guidelines are a little different. Maybe we should reconsider some of these guidelines based on these data.”
David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., who is not involved in the TAVR studies, said: “The results provide a little more reassurance ... that will go a little way further.”
“Uncertainty remains regarding long-term durability of the transcatheter valve in low-risk patients who are generally younger and likely more active than higher-risk cohorts,” he added. “The current 3-year results provide more confidence as the outcome curves for death and disabling stroke are trending in the right direction for TAVR versus surgery.”
Dr. Moliterno pointed out that while rates of paravalvular regurgitation and permanent pacemaker placement are decreasing with newer generation Evolut devices and implantation techniques, he noted that according to the U.S. Social Security Administration, patients aged 74 years as enrolled in this low-risk cohort have an additional life expectancy of approximately 12 years. “So, we have more device durability (and coronary access feasibility) to prove.”
In his presentation, Dr. Forrest explained that TAVR is now approved in the United States for all patients with aortic stenosis regardless of surgical risk and has become the dominant form of aortic valve replacement. Current ACC/AHA guidelines recommend that heart teams utilize a shared decision-making process when discussing aortic valve replacement with patients aged 65-80 years. In younger, lower-risk patients, the faster recovery and short-term benefits after TAVR must be balanced with long-term durability; however, only limited intermediate and long-term data exist to guide such discussions in this patient population.
The Evolut Low Risk trial randomly assigned 1,414 patients in need of aortic valve replacement to TAVR with a self-expanding, supra-annular valve or surgery. Results at 1 and 2 years have shown a similar benefit in the primary endpoint of all-cause mortality/disabling stroke for the less invasive TAVR procedure.
The current 3-year results suggest the benefit appears to be maintained out for another year.
The main results show that the rate of death or disabling stroke was 7.4% in the TAVR group versus 10.4% in the surgery group, giving a hazard ratio of 0.70 (P = .051).
In the JACC paper, the authors report that the absolute difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: –1.8% at year 1; –2.0% at year 2; and –2.9% at year 3.
Other key results on valve durability show that mild paravalvular regurgitation was increased in the TAVR group (20.3%) versus 2.5% with surgery. However, rates of moderate or greater paravalvular regurgitation for both groups were below 1% and not significantly different between groups.
Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1 mm Hg TAVR vs. 12.1 mm Hg surgery; P < .001) at 3 years.
However, pacemaker placement was much higher in the TAVR group (23.2%), compared with 9.1% in the surgery group.
On the other hand, the surgery group had a greater incidence of atrial fibrillation (40%) versus 13% with TAVR.
Quality-of-life results looked good in both groups.
“As we’ve come to expect, patients recover more quickly after TAVR, so at 30 days their quality of life is better than those who have undergone surgery,” Dr. Forrest commented. “But by 1 year, both groups are doing exceptionally well and, remarkably, here by 3 years both groups have greater than a 20-point increase in their KCCQ score, showing a very large improvement in quality of life.”
Discussant of these latest results at the ACC late-breaking trials session, James Hermiller, MD, St. Vincent Ascension Heart Center, Indianapolis, said: “This 3-year data continues to demonstrate that the gift of TAVR keeps giving.”
Noting that the divergence in the effect curves was primarily driven by mortality rather than stroke, he asked whether this was cardiac or noncardiac mortality that was reduced.
Dr. Forrest responded: “It was a fairly equal contribution – a little bit more cardiac death. We have to remember that although the average age in this study was 74, there were some patients over 80 who were still low-surgical-risk included so we are going to see noncardiac death as well.”
Dr. Hermiller drew attention to the high pacemaker rate in the TAVR group and asked how these patients fared in comparison to those who didn’t need a pacemaker.
Dr. Forrest replied: “I think it’s fair to say that putting in a pacemaker is not a benign procedure. Patients who got a pacemaker did slightly worse than those who didn’t get a pacemaker, so we need to try to drive that rate down.”
He added that the number of patients needing a pacemaker after TAVR has come down with new implantation techniques and new generation valves.
“We realize that using a cusp overlap technique can significantly reduce the need for a pacemaker, and we see from registry data that with the use of this new technique the need for a pacemaker has dropped down to 8%-9%, significantly less than seen in this study,” Dr. Forrest commented.
Dr. Hermiller also asked about how TAVR affects future access for catheterization or percutaneous coronary intervention.
Dr. Forrest noted that 24 patients in the TAVR group required PCI in first 3 years, and all the PCI procedures had been successful. He noted that operators reported the procedure to be easy or moderately easy in about 75%-80% of cases and difficult in about 20% of patients. “So, it is slightly more challenging to engage the coronaries and have to go through the frame, but it is very feasible.”
Dr. Forrest concluded that: “These results provide patients and heart teams important data to aid in the shared decision-making process.”
But he acknowledged that longer term data are still needed. “And the potential impact that hemodynamics, valve design, new pacemakers, and other secondary endpoints have on long-term outcomes will be important to follow in this group of low-risk patients.”
The Evolut Low Risk trial was funded by Medtronic. Dr. Forrest has received grant support/research contracts and consultant fees/honoraria/speakers bureau fees from Edwards Lifesciences and Medtronic.
A version of this article first appeared on Medscape.com.
Three-year results from the Evolut trial seem to provide more reassurance on the use of transcatheter aortic valve replacement (TAVR) in low-surgical-risk patients.
The 3-year results show that low-surgical-risk patients undergoing aortic valve replacement continue to show lower rates of all-cause mortality and disabling stroke with TAVR, compared with surgery.
The rates of all-cause mortality or disabling stroke (the primary endpoint) at 3 years were 7.4% with TAVR and 10.4% with surgery.
Rates of new pacemaker implantation continued to be higher after TAVR and the frequency of new onset atrial fibrillation was more common after surgery.
“At 3 years, the rate of all-cause mortality or disabling stroke after TAVR with the Evolut valve compared very favorably to surgery. The absolute difference between treatment arms remained consistent with a 30% relative reduction in the hazard of death or disabling stroke, with a P value that just missed statistical significance,” said Evolut investigator John Forrest, MD, Yale University School of Medicine, New Haven, Conn.
“The Kaplan-Meier curves show what we’ve come to expect – an early separation of the curves – but what’s unique here, and seen for the first time, is that the early separation is maintained at year 1 and year 2, and between years 2 and 3 the curve didn’t start to come together, but, if anything, separated a little,” Dr. Forrest commented.
“Both components of the primary endpoint – all cause mortality and disabling stroke – numerically favor TAVR. The separation of the curves for stroke are maintained, and if anything, we see a further slight separation of the curves as we go forward out to 3 years in terms of all-cause mortality,” he added.
Dr. Forrest presented the 3-year results from the Evolut trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. They were simultaneously published online in the Journal of the American College of Cardiology.
Dr. Forrest also reported that TAVR patients continued to have better valve hemodynamics at 3 years and very low rates of valve thrombosis; moreover, rates of moderate or greater paravalvular regurgitation and paravalvular leak (factors that can affect valve durability) were also low, although mild paravalvular regurgitation was higher with TAVR.
“In these low-risk patients, the durability of the valve is going to be critically important,” Dr. Forrest commented. “The excellent valve performance and durable outcomes out to 3 years in low-risk patients affirms the role of TAVR in this population,” he concluded.
On how these results may affect clinical practice, Dr. Forrest said: “I think in the U.S. these results reaffirm what we are doing. It gives us confidence to continue treating low-risk patients and being comfortable with that.”
He added: “Outside the U.S., the guidelines are a little different. Maybe we should reconsider some of these guidelines based on these data.”
David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., who is not involved in the TAVR studies, said: “The results provide a little more reassurance ... that will go a little way further.”
“Uncertainty remains regarding long-term durability of the transcatheter valve in low-risk patients who are generally younger and likely more active than higher-risk cohorts,” he added. “The current 3-year results provide more confidence as the outcome curves for death and disabling stroke are trending in the right direction for TAVR versus surgery.”
Dr. Moliterno pointed out that while rates of paravalvular regurgitation and permanent pacemaker placement are decreasing with newer generation Evolut devices and implantation techniques, he noted that according to the U.S. Social Security Administration, patients aged 74 years as enrolled in this low-risk cohort have an additional life expectancy of approximately 12 years. “So, we have more device durability (and coronary access feasibility) to prove.”
In his presentation, Dr. Forrest explained that TAVR is now approved in the United States for all patients with aortic stenosis regardless of surgical risk and has become the dominant form of aortic valve replacement. Current ACC/AHA guidelines recommend that heart teams utilize a shared decision-making process when discussing aortic valve replacement with patients aged 65-80 years. In younger, lower-risk patients, the faster recovery and short-term benefits after TAVR must be balanced with long-term durability; however, only limited intermediate and long-term data exist to guide such discussions in this patient population.
The Evolut Low Risk trial randomly assigned 1,414 patients in need of aortic valve replacement to TAVR with a self-expanding, supra-annular valve or surgery. Results at 1 and 2 years have shown a similar benefit in the primary endpoint of all-cause mortality/disabling stroke for the less invasive TAVR procedure.
The current 3-year results suggest the benefit appears to be maintained out for another year.
The main results show that the rate of death or disabling stroke was 7.4% in the TAVR group versus 10.4% in the surgery group, giving a hazard ratio of 0.70 (P = .051).
In the JACC paper, the authors report that the absolute difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: –1.8% at year 1; –2.0% at year 2; and –2.9% at year 3.
Other key results on valve durability show that mild paravalvular regurgitation was increased in the TAVR group (20.3%) versus 2.5% with surgery. However, rates of moderate or greater paravalvular regurgitation for both groups were below 1% and not significantly different between groups.
Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1 mm Hg TAVR vs. 12.1 mm Hg surgery; P < .001) at 3 years.
However, pacemaker placement was much higher in the TAVR group (23.2%), compared with 9.1% in the surgery group.
On the other hand, the surgery group had a greater incidence of atrial fibrillation (40%) versus 13% with TAVR.
Quality-of-life results looked good in both groups.
“As we’ve come to expect, patients recover more quickly after TAVR, so at 30 days their quality of life is better than those who have undergone surgery,” Dr. Forrest commented. “But by 1 year, both groups are doing exceptionally well and, remarkably, here by 3 years both groups have greater than a 20-point increase in their KCCQ score, showing a very large improvement in quality of life.”
Discussant of these latest results at the ACC late-breaking trials session, James Hermiller, MD, St. Vincent Ascension Heart Center, Indianapolis, said: “This 3-year data continues to demonstrate that the gift of TAVR keeps giving.”
Noting that the divergence in the effect curves was primarily driven by mortality rather than stroke, he asked whether this was cardiac or noncardiac mortality that was reduced.
Dr. Forrest responded: “It was a fairly equal contribution – a little bit more cardiac death. We have to remember that although the average age in this study was 74, there were some patients over 80 who were still low-surgical-risk included so we are going to see noncardiac death as well.”
Dr. Hermiller drew attention to the high pacemaker rate in the TAVR group and asked how these patients fared in comparison to those who didn’t need a pacemaker.
Dr. Forrest replied: “I think it’s fair to say that putting in a pacemaker is not a benign procedure. Patients who got a pacemaker did slightly worse than those who didn’t get a pacemaker, so we need to try to drive that rate down.”
He added that the number of patients needing a pacemaker after TAVR has come down with new implantation techniques and new generation valves.
“We realize that using a cusp overlap technique can significantly reduce the need for a pacemaker, and we see from registry data that with the use of this new technique the need for a pacemaker has dropped down to 8%-9%, significantly less than seen in this study,” Dr. Forrest commented.
Dr. Hermiller also asked about how TAVR affects future access for catheterization or percutaneous coronary intervention.
Dr. Forrest noted that 24 patients in the TAVR group required PCI in first 3 years, and all the PCI procedures had been successful. He noted that operators reported the procedure to be easy or moderately easy in about 75%-80% of cases and difficult in about 20% of patients. “So, it is slightly more challenging to engage the coronaries and have to go through the frame, but it is very feasible.”
Dr. Forrest concluded that: “These results provide patients and heart teams important data to aid in the shared decision-making process.”
But he acknowledged that longer term data are still needed. “And the potential impact that hemodynamics, valve design, new pacemakers, and other secondary endpoints have on long-term outcomes will be important to follow in this group of low-risk patients.”
The Evolut Low Risk trial was funded by Medtronic. Dr. Forrest has received grant support/research contracts and consultant fees/honoraria/speakers bureau fees from Edwards Lifesciences and Medtronic.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
‘Keto-like’ diet linked to doubling of heart disease risk
Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.
“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.
“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.
Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.
In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.
“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”
He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.”
For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.
They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.
On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.
Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).
Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).
Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004). Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).
After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.
After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
‘Closer monitoring needed’
“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”
He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.
“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”
He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001).
“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”
Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.
“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
Jury still out
Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”
Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.
“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said.
“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.
The authors of the study reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.
“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.
“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.
Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.
In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.
“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”
He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.”
For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.
They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.
On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.
Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).
Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).
Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004). Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).
After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.
After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
‘Closer monitoring needed’
“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”
He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.
“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”
He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001).
“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”
Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.
“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
Jury still out
Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”
Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.
“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said.
“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.
The authors of the study reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.
“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.
“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.
Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.
In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.
“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”
He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.”
For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.
They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.
On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.
Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).
Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).
Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004). Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).
After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.
After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
‘Closer monitoring needed’
“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”
He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.
“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”
He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001).
“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”
Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.
“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
Jury still out
Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”
Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.
“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said.
“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.
The authors of the study reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ACC 2023
Heart-healthy actions promote longer, disease-free life
Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.
The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.
In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.
CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.
The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.
Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.
The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.
The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.
In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.
Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.
The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.
For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.
Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).
Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.
The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.
The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.
More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.
“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.
People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.
The meeting was sponsored by the American Heart Association.
Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.
The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.
In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.
CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.
The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.
Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.
The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.
The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.
In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.
Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.
The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.
For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.
Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).
Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.
The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.
The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.
More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.
“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.
People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.
The meeting was sponsored by the American Heart Association.
Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
Adults who follow a heart-healthy lifestyle are more likely to live longer and to be free of chronic health conditions, based on data from a pair of related studies from the United States and United Kingdom involving nearly 200,000 individuals.
The studies, presented at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting in Boston, assessed the impact of cardiovascular health on life expectancy and freedom from chronic diseases. Cardiovascular health (CVH) was based on the Life’s Essential 8 (LE8) score, a composite of health metrics released by the American Heart Association in 2022. The LE8 was developed to guide research and assessment of cardiovascular health, and includes diet, physical activity, tobacco/nicotine exposure, sleep, body mass index, non-HDL cholesterol, blood glucose, and blood pressure.
In one study, Xuan Wang, MD, a postdoctoral fellow and biostatistician in the department of epidemiology at Tulane University, New Orleans, and colleagues reviewed data from 136,599 adults in the United Kingdom Biobank who were free of cardiovascular disease, diabetes, cancer, and dementia at baseline, and for whom complete LE8 data were available.
CVH was classified as poor, intermediate, and ideal, defined as LE8 scores of less than 50, 50 to 80, and 80 or higher, respectively.
The goal of the study was to examine the role of CVH based on LE8 scores on the percentage of life expectancy free of chronic diseases.
Men and women with ideal CVH averaged 5.2 years and 6.3 years more of total life expectancy at age 50 years, compared with those with poor CVH. Out of total life expectancy, the percentage of life expectancy free of chronic diseases was 75.9% and 83.4% for men and women, respectively, compared with 64.9% and 69.4%, respectively, for men and women with poor CVH.
The researchers also found that disparities in the percentage of disease-free years for both men and women were reduced in the high CVH groups.
The findings were limited by several factors including the use of only CVD, diabetes, cancer, and dementia in the definition of “disease-free life expectancy,” the researchers noted in a press release accompanying the study. Other limitations include the lack of data on e-cigarettes, and the homogeneous White study population. More research is needed in diverse populations who experience a stronger impact from negative social determinants of health, they said.
In a second study, Hao Ma, MD, and colleagues reviewed data from 23,003 adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 with mortality linked to the National Death Index through Dec. 31, 2019. The goal of the second study was to examine the association between CVH based on LE8 scores and life expectancy.
Over a median follow-up of 7.8 years, deaths occurred in 772 men and 587 women, said Dr. Ma, a postdoctoral fellow and biostatistician in epidemiology at Tulane University and coauthor on Dr. Wang’s study.
The estimated life expectancies at age 50 years for men with poor, intermediate, and ideal cardiovascular health based on the LE8 were 25.5 years, 31.2 years, and 33.1 years, respectively.
For women, the corresponding life expectancies for women at age 50 with poor, intermediate, and ideal CVH were 29.5 years, 34.2 years, and 38.4 years, respectively.
Men and women had similar gains in life expectancy from adhering to a heart-healthy lifestyle as defined by the LE8 score that reduced their risk of death from cardiovascular disease (41.8% and 44.1%, respectively).
Associations of cardiovascular health and life expectancy were similar for non-Hispanic Whites and non-Hispanic Blacks, but not among people of Mexican heritage, and more research is needed in diverse populations, the researchers wrote.
The study was limited by several factors including potential changes in cardiovascular health during the follow-up period, and by the limited analysis of racial and ethnic groups to non-Hispanic white, non-Hispanic Black, and people of Mexican heritage because of small sample sizes for other racial/ethnic groups, the researchers noted in a press release accompanying the study.
The message for clinicians and their patients is that adherence to cardiovascular health as defined by the LE8 will help not only extend life, but enhance quality of life, Dr. Xang and Dr. Ma said in an interview. “If your overall CVH score is low, we might be able to focus on one element first and improve them one by one,” they said. Sedentary lifestyle and an unhealthy diet are barriers to improving LE8 metrics that can be addressed, they added.
More research is needed to examine the effects of LE8 on high-risk patients, the researchers told this news organization. “No studies have yet focused on these patients with chronic diseases. We suspect that LE8 will play a role even in these high-risk groups,” they said. Further studies should include diverse populations and evaluations of the association between CVH change and health outcomes, they added.
“Overall, we see this 7.5-year difference [in life expectancy] going from poor to high cardiovascular health,” said Donald M. Lloyd-Jones, MD, of Northwestern University, Chicago, in a video accompanying the presentation of the study findings. The impact on life expectancy is yet another reason to motivate people to improve their cardiovascular health, said Dr. Lloyd-Jones, immediate past president of the American Heart Association and lead author on the writing group for Life’s Essential 8. “The earlier we do this, the better, and the greater the gains in life expectancy we’re likely to see in the U.S. population,” he said.
People maintaining high cardiovascular health into midlife are avoiding not only cardiovascular disease, but other chronic diseases of aging, Dr. Lloyd-Jones added. These conditions are delayed until much later in the lifespan, which allows people to enjoy better quality of life for more of their remaining years, he said.
The meeting was sponsored by the American Heart Association.
Both studies were supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health; the Fogarty International Center; and the Tulane Research Centers of Excellence Awards. The researchers had no financial conflicts to disclose.
FROM EPI/LIFESTYLE 2023
High CV risk factor burden in young adults a ‘smoldering’ crisis
New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.
In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.
Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.
The findings are “extremely concerning. We’re witnessing a smoldering public health crisis. The onset of these risk factors earlier in life is associated with a higher lifetime risk of heart disease and potentially life-threatening,” Dr. Wadhera added.
The study was presented March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation and was simultaneously published in JAMA.
The burden of CV risk factors among young adults is “unacceptably high and increasing,” write the co-authors of a JAMA editorial.
“The time is now for aggressive preventive measures in young adults. Without immediate action there will continue to be a rise in heart disease and the burden it places on patients, families, and communities,” say Norrina Allen, PhD, and John Wilkins, MD, with Northwestern University, Chicago.
Preventing a tsunami of heart disease
The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.
Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.
Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).
Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.
The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).
“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.
“Even in the lipid control, while it did get a little bit better, it’s still only around 30%-40%. So, I think we have ways to go as a society,” Dr. Berger noted.
Double down on screening
Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”
“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.
Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”
As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”
“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.
“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.
In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”
The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.
In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.
Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.
The findings are “extremely concerning. We’re witnessing a smoldering public health crisis. The onset of these risk factors earlier in life is associated with a higher lifetime risk of heart disease and potentially life-threatening,” Dr. Wadhera added.
The study was presented March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation and was simultaneously published in JAMA.
The burden of CV risk factors among young adults is “unacceptably high and increasing,” write the co-authors of a JAMA editorial.
“The time is now for aggressive preventive measures in young adults. Without immediate action there will continue to be a rise in heart disease and the burden it places on patients, families, and communities,” say Norrina Allen, PhD, and John Wilkins, MD, with Northwestern University, Chicago.
Preventing a tsunami of heart disease
The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.
Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.
Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).
Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.
The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).
“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.
“Even in the lipid control, while it did get a little bit better, it’s still only around 30%-40%. So, I think we have ways to go as a society,” Dr. Berger noted.
Double down on screening
Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”
“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.
Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”
As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”
“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.
“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.
In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”
The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data show a high and rising burden of most cardiovascular (CV) risk factors among young adults aged 20-44 years in the United States.
In this age group, over the past 10 years, there has been an increase in the prevalence of diabetes and obesity, no improvement in the prevalence of hypertension, and a decrease in the prevalence of hyperlipidemia.
Yet medical treatment rates for CV risk factors are “surprisingly” low among young adults, study investigator Rishi Wadhera, MD, with Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, told this news organization.
The findings are “extremely concerning. We’re witnessing a smoldering public health crisis. The onset of these risk factors earlier in life is associated with a higher lifetime risk of heart disease and potentially life-threatening,” Dr. Wadhera added.
The study was presented March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation and was simultaneously published in JAMA.
The burden of CV risk factors among young adults is “unacceptably high and increasing,” write the co-authors of a JAMA editorial.
“The time is now for aggressive preventive measures in young adults. Without immediate action there will continue to be a rise in heart disease and the burden it places on patients, families, and communities,” say Norrina Allen, PhD, and John Wilkins, MD, with Northwestern University, Chicago.
Preventing a tsunami of heart disease
The findings stem from a cross-sectional study of 12,294 U.S. adults aged 20-44 years (mean age, 32; 51% women) who participated in National Health and Nutrition Examination Survey (NHANES) cycles for 2009-2010 to 2017-2020.
Overall, the prevalence of hypertension was 9.3% in 2009-2010 and increased to 11.5% in 2017-2020. The prevalence of diabetes rose from 3.0% to 4.1%, and the prevalence of obesity rose from 32.7% to 40.9%. The prevalence of hyperlipidemia decreased from 40.5% to 36.1%.
Black adults consistently had high rates of hypertension during the study period – 16.2% in 2009-2010 and 20.1% in 2017-2020 – and significant increases in hypertension occurred among Mexican American adults (from 6.5% to 9.5%) and other Hispanic adults (from 4.4% to 10.5%), while Mexican American adults had a significant uptick in diabetes (from 4.3% to 7.5%).
Equally concerning, said Dr. Wadhera, is the fact that only about 55% of young adults with hypertension were receiving antihypertensive medication, and just 1 in 2 young adults with diabetes were receiving treatment. “These low rates were driven, in part, by many young adults not being aware of their diagnosis,” he noted.
The NHANES data also show that the percentage of young adults who were treated for hypertension and who achieved blood pressure control did not change significantly over the study period (65.0% in 2009-2010 and 74.8% in 2017-2020). Blood sugar control among young adults being treated for diabetes remained suboptimal throughout the study period (45.5% in 2009-2010 and 56.6% in 2017-2020).
“The fact that blood pressure control and glycemic control are so poor is really worrisome,” Jeffrey Berger, MD, director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, who wasn’t involved in the study, told this news organization.
“Even in the lipid control, while it did get a little bit better, it’s still only around 30%-40%. So, I think we have ways to go as a society,” Dr. Berger noted.
Double down on screening
Dr. Wadhera said “we need to double down on efforts to screen for and treat cardiovascular risk factors like high blood pressure and diabetes in young adults. We need to intensify clinical and public health interventions focused on primordial and primary prevention in young adults now so that we can avoid a tsunami of cardiovascular disease in the long term.”
“It’s critically important that young adults speak with their health care provider about whether – and when – they should undergo screening for high blood pressure, diabetes, and high cholesterol,” Dr. Wadhera added.
Dr. Berger said one problem is that younger people often have a “superman or superwoman” view and don’t comprehend that they are at risk for some of these conditions. Studies such as this “reinforce the idea that it’s never too young to be checked out.”
As a cardiologist who specializes in cardiovascular prevention, Dr. Berger said he sometimes hears patients say things like, “I don’t ever want to need a cardiologist,” or “I hope I never need a cardiologist.”
“My response is, ‘There are many different types of cardiologists,’ and I think it would really be helpful for many people to see a prevention-focused cardiologist way before they have problems,” he said in an interview.
“As a system, medicine has become very good at treating patients with different diseases. I think we need to get better in terms of preventing some of these problems,” Dr. Berger added.
In their editorial, Dr. Allen and Dr. Wilkins say the “foundation of cardiovascular health begins early in life. These worsening trends in risk factors highlight the importance of focusing on prevention in adolescence and young adulthood in order to promote cardiovascular health across the lifetime.”
The study was funded by a grant from the National Heart, Lung, and Blood Institute. Dr. Wadhera has served as a consultant for Abbott and CVS Health. Dr. Wilkins has received personal fees from 3M. Dr. Berger has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACC 2023
44-year-old man • elevated total cholesterol • chest pains • ketogenic diet • Dx?
THE CASE
A 44-year-old man with a history of morbid obesity reestablished care in our clinic. He had been treated in our health care system about 5 years previously, and prior lab testing showed a total cholesterol of 203 mg/dL; triglycerides, 191 mg/dL; high-density lipoprotein (HDL), 56 mg/dL; and low-density lipoprotein (LDL), 109 mg/dL. At that time, he weighed 299 lbs (BMI, 39.4). He then started a strict ketogenic diet and a regular exercise program (running ~ 16 miles per week and lifting weights), which he maintained for several years. He had experienced remarkable weight loss; upon reestablishing care, he weighed 199 lbs (BMI, 26.33).
However, lipid testing revealed a severely elevated total cholesterol of 334 mg/dL; LDL, 248 mg/dL; HDL, 67 mg/dL; and triglycerides, 95 mg/dL. He was advised to start statin therapy and to stop his ketogenic diet, but he was hesitant to take either step. He elected to have his lab work reevaluated in 6 months.
About 4 months later, he presented with new and increasing burning pain in his mid chest and upper abdomen. He rated the pain 6/10 in severity and said it occurred during exertion or at night when lying down. Resting would relieve the pain. Reduced intake of spicy foods and caffeine had also helped. He denied dyspnea, diaphoresis, palpitations, or nausea.
The patient was a nonsmoker but did have a strong family history of cardiovascular disease. His vital signs and physical examination were unremarkable, apart from mild epigastric and periumbilical tenderness on palpation.
THE DIAGNOSIS
The patient’s chest pain had features of both gastroesophageal reflux disease (GERD) and coronary artery disease (CAD) with exertional angina. His high-fat diet, nightly symptoms, and the partial relief he achieved by cutting back on spicy foods and caffeine suggested GERD, but the exertional nature of the chest pain and gradual relief with rest was highly suggestive of angina, so an outpatient electrocardiogram treadmill stress test was ordered.
The stress test was markedly abnormal, showing worsening ST depressions and T-wave inversions with exertion, and he experienced chest pain during testing. An urgent left heart catheterization was performed, showing severe multivessel CAD. He subsequently underwent 3-vessel coronary artery bypass grafting. A familial hypercholesterolemia panel failed to reveal any significant variants.
As a result of these findings, the patient received a diagnosis of severe ketogenic diet–associated hypercholesterolemia and early-onset CAD.
Continue to: DISCUSSION
DISCUSSION
Low-carbohydrate (low-carb) and ketogenic diets have grown in popularity throughout the United States over the past decade, particularly for weight loss, and the diet has entered the popular consciousness with several celebrities publicly supporting it.1 Simultaneously, there also has been a growing interest in these diets for the treatment of chronic diseases, such as type 2 diabetes.2 However, the long-term cardiovascular effects of low-carb diets are not well studied, and there is significant heterogeneity among these diets.
Low-carb vs low-fat. Multiple meta-analyses comparing low-carb diets to low-fat diets have found that those following low-carb diets have significantly higher total cholesterol and LDL levels.3,4,5 The National Lipid Association’s review of evidence determined that LDL and total cholesterol responses vary in individuals following a low-carb diet, but that increasing LDL levels in particular were concerning enough to warrant lipid monitoring of patients on low-carb diets.6 Another meta-analysis evaluated the difference in estimated atherosclerotic cardiovascular disease (ASCVD) risk between low-carb and low-fat diets, finding those following a low-carb diet to have a lower estimated ASCVD risk but higher LDL levels.7
Weighing the benefits and harms. Since our patient’s dramatic weight loss and greatly increased exercise level would be expected to lower his LDL levels, the severe worsening of his LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD. The benefits of low-carb diets for weight loss, contrasted with the consistent worsening of LDL levels, has prompted a debate about which parameters should be considered in estimating the long-term risk of these diets for patients. Diamond et al8 posit that these diets have beneficial effects on “the most reliable [cardiovascular disease] risk factors,” but long-term, patient-oriented outcome data are lacking, and these diets may not be appropriate for certain patients, as our case demonstrates.
A reasonable strategy for patients contemplating a low-carb diet specifically for weight loss would be to use such a diet for 3 to 6 months to achieve initial and rapid results, then continue with a heart-healthy diet and increased exercise levels to maintain weight loss and reduce long-term cardiovascular risk.
Our patient was started on a postoperative medication regimen of aspirin 81 mg/d, evolocumab 140 mg every 14 days, metoprolol tartrate 25 mg bid, and rosuvastatin 10 mg/d. A year later, he was able to resume a high level of physical activity (6-mile runs) without chest pain. His follow-up lipid panel showed a total cholesterol of 153 mg/dL; LDL, 53 mg/dL; HDL, 89 mg/dL; and triglycerides, 55 mg/dL. He had also switched to a regular diet and had been able to maintain his weight loss.
THE TAKEAWAY
Growing evidence suggests that low-carb diets may have a significant and detrimental effect on LDL levels. The long-term safety of these diets hasn’t been well studied, particularly regarding cardiovascular outcomes. At a minimum, patients who initiate low-carb diets should be counseled on general dietary recommendations regarding saturated fat and cholesterol intake, and they should have a follow-up lipid screening to evaluate for any significant worsening in total cholesterol and LDL levels.
CORRESPONDENCE
Samuel Dickmann, MD, 13611 NW 1st Lane, Suite 200, Newberry, FL 32669; [email protected]
1. Gorin A. What is the keto diet – and is it right for you? NBC News BETTER. February 22, 2018. Accessed February 3, 2023. www.nbcnews.com/better/health/what-keto-diet-it-right-you-ncna847256
2. Tinguely D, Gross J, Kosinski, C. Efficacy of ketogenic diets on type 2 diabetes: a systematic review. Current Diabetes Reports. 2021;21:32. doi: 10.1007/s11892-021-01399-z
3. Mansoor N, Vinknes KJ, Veierod MB, et al. Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors a meta-analysis of randomised controlled trials. Br J Nutr. 2016;115:466-479. doi: 10.1017/S0007114515004699
4. Bueno NB, de Melo ISV, de Oliveira SL, et al. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110:1178-1187. doi: 10.1017/S0007114513000548
5. Chawla S, Tessarolo Silva F, Amaral Medeiros S, et al. The effect of low-fat and low-carbohydrate diets on weight loss and lipid levels: a systematic review and meta-analysis. Nutrients. 2020;12:3774. doi: 10.3390/nu12123774
6. Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: a scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. J Clin Lipidol. 2019;13:689-711.e1. doi: 10.1016/j.jacl.2019.08.003
7. Sackner-Bernstein J, Kanter D, Kaul S. Dietary intervention for overweight and obese adults: comparison of low-carbohydrate and low-fat diets. a meta-analysis. PLoS One. 2015;10:e0139817. doi: 10.1371/journal.pone.0139817
8. Diamond DM, O’Neill BJ, Volek JS. Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified? Curr Opin Endocrinol Diabetes Obes. 2020;27:291-300. doi: 10.1097/MED.0000000000000568
THE CASE
A 44-year-old man with a history of morbid obesity reestablished care in our clinic. He had been treated in our health care system about 5 years previously, and prior lab testing showed a total cholesterol of 203 mg/dL; triglycerides, 191 mg/dL; high-density lipoprotein (HDL), 56 mg/dL; and low-density lipoprotein (LDL), 109 mg/dL. At that time, he weighed 299 lbs (BMI, 39.4). He then started a strict ketogenic diet and a regular exercise program (running ~ 16 miles per week and lifting weights), which he maintained for several years. He had experienced remarkable weight loss; upon reestablishing care, he weighed 199 lbs (BMI, 26.33).
However, lipid testing revealed a severely elevated total cholesterol of 334 mg/dL; LDL, 248 mg/dL; HDL, 67 mg/dL; and triglycerides, 95 mg/dL. He was advised to start statin therapy and to stop his ketogenic diet, but he was hesitant to take either step. He elected to have his lab work reevaluated in 6 months.
About 4 months later, he presented with new and increasing burning pain in his mid chest and upper abdomen. He rated the pain 6/10 in severity and said it occurred during exertion or at night when lying down. Resting would relieve the pain. Reduced intake of spicy foods and caffeine had also helped. He denied dyspnea, diaphoresis, palpitations, or nausea.
The patient was a nonsmoker but did have a strong family history of cardiovascular disease. His vital signs and physical examination were unremarkable, apart from mild epigastric and periumbilical tenderness on palpation.
THE DIAGNOSIS
The patient’s chest pain had features of both gastroesophageal reflux disease (GERD) and coronary artery disease (CAD) with exertional angina. His high-fat diet, nightly symptoms, and the partial relief he achieved by cutting back on spicy foods and caffeine suggested GERD, but the exertional nature of the chest pain and gradual relief with rest was highly suggestive of angina, so an outpatient electrocardiogram treadmill stress test was ordered.
The stress test was markedly abnormal, showing worsening ST depressions and T-wave inversions with exertion, and he experienced chest pain during testing. An urgent left heart catheterization was performed, showing severe multivessel CAD. He subsequently underwent 3-vessel coronary artery bypass grafting. A familial hypercholesterolemia panel failed to reveal any significant variants.
As a result of these findings, the patient received a diagnosis of severe ketogenic diet–associated hypercholesterolemia and early-onset CAD.
Continue to: DISCUSSION
DISCUSSION
Low-carbohydrate (low-carb) and ketogenic diets have grown in popularity throughout the United States over the past decade, particularly for weight loss, and the diet has entered the popular consciousness with several celebrities publicly supporting it.1 Simultaneously, there also has been a growing interest in these diets for the treatment of chronic diseases, such as type 2 diabetes.2 However, the long-term cardiovascular effects of low-carb diets are not well studied, and there is significant heterogeneity among these diets.
Low-carb vs low-fat. Multiple meta-analyses comparing low-carb diets to low-fat diets have found that those following low-carb diets have significantly higher total cholesterol and LDL levels.3,4,5 The National Lipid Association’s review of evidence determined that LDL and total cholesterol responses vary in individuals following a low-carb diet, but that increasing LDL levels in particular were concerning enough to warrant lipid monitoring of patients on low-carb diets.6 Another meta-analysis evaluated the difference in estimated atherosclerotic cardiovascular disease (ASCVD) risk between low-carb and low-fat diets, finding those following a low-carb diet to have a lower estimated ASCVD risk but higher LDL levels.7
Weighing the benefits and harms. Since our patient’s dramatic weight loss and greatly increased exercise level would be expected to lower his LDL levels, the severe worsening of his LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD. The benefits of low-carb diets for weight loss, contrasted with the consistent worsening of LDL levels, has prompted a debate about which parameters should be considered in estimating the long-term risk of these diets for patients. Diamond et al8 posit that these diets have beneficial effects on “the most reliable [cardiovascular disease] risk factors,” but long-term, patient-oriented outcome data are lacking, and these diets may not be appropriate for certain patients, as our case demonstrates.
A reasonable strategy for patients contemplating a low-carb diet specifically for weight loss would be to use such a diet for 3 to 6 months to achieve initial and rapid results, then continue with a heart-healthy diet and increased exercise levels to maintain weight loss and reduce long-term cardiovascular risk.
Our patient was started on a postoperative medication regimen of aspirin 81 mg/d, evolocumab 140 mg every 14 days, metoprolol tartrate 25 mg bid, and rosuvastatin 10 mg/d. A year later, he was able to resume a high level of physical activity (6-mile runs) without chest pain. His follow-up lipid panel showed a total cholesterol of 153 mg/dL; LDL, 53 mg/dL; HDL, 89 mg/dL; and triglycerides, 55 mg/dL. He had also switched to a regular diet and had been able to maintain his weight loss.
THE TAKEAWAY
Growing evidence suggests that low-carb diets may have a significant and detrimental effect on LDL levels. The long-term safety of these diets hasn’t been well studied, particularly regarding cardiovascular outcomes. At a minimum, patients who initiate low-carb diets should be counseled on general dietary recommendations regarding saturated fat and cholesterol intake, and they should have a follow-up lipid screening to evaluate for any significant worsening in total cholesterol and LDL levels.
CORRESPONDENCE
Samuel Dickmann, MD, 13611 NW 1st Lane, Suite 200, Newberry, FL 32669; [email protected]
THE CASE
A 44-year-old man with a history of morbid obesity reestablished care in our clinic. He had been treated in our health care system about 5 years previously, and prior lab testing showed a total cholesterol of 203 mg/dL; triglycerides, 191 mg/dL; high-density lipoprotein (HDL), 56 mg/dL; and low-density lipoprotein (LDL), 109 mg/dL. At that time, he weighed 299 lbs (BMI, 39.4). He then started a strict ketogenic diet and a regular exercise program (running ~ 16 miles per week and lifting weights), which he maintained for several years. He had experienced remarkable weight loss; upon reestablishing care, he weighed 199 lbs (BMI, 26.33).
However, lipid testing revealed a severely elevated total cholesterol of 334 mg/dL; LDL, 248 mg/dL; HDL, 67 mg/dL; and triglycerides, 95 mg/dL. He was advised to start statin therapy and to stop his ketogenic diet, but he was hesitant to take either step. He elected to have his lab work reevaluated in 6 months.
About 4 months later, he presented with new and increasing burning pain in his mid chest and upper abdomen. He rated the pain 6/10 in severity and said it occurred during exertion or at night when lying down. Resting would relieve the pain. Reduced intake of spicy foods and caffeine had also helped. He denied dyspnea, diaphoresis, palpitations, or nausea.
The patient was a nonsmoker but did have a strong family history of cardiovascular disease. His vital signs and physical examination were unremarkable, apart from mild epigastric and periumbilical tenderness on palpation.
THE DIAGNOSIS
The patient’s chest pain had features of both gastroesophageal reflux disease (GERD) and coronary artery disease (CAD) with exertional angina. His high-fat diet, nightly symptoms, and the partial relief he achieved by cutting back on spicy foods and caffeine suggested GERD, but the exertional nature of the chest pain and gradual relief with rest was highly suggestive of angina, so an outpatient electrocardiogram treadmill stress test was ordered.
The stress test was markedly abnormal, showing worsening ST depressions and T-wave inversions with exertion, and he experienced chest pain during testing. An urgent left heart catheterization was performed, showing severe multivessel CAD. He subsequently underwent 3-vessel coronary artery bypass grafting. A familial hypercholesterolemia panel failed to reveal any significant variants.
As a result of these findings, the patient received a diagnosis of severe ketogenic diet–associated hypercholesterolemia and early-onset CAD.
Continue to: DISCUSSION
DISCUSSION
Low-carbohydrate (low-carb) and ketogenic diets have grown in popularity throughout the United States over the past decade, particularly for weight loss, and the diet has entered the popular consciousness with several celebrities publicly supporting it.1 Simultaneously, there also has been a growing interest in these diets for the treatment of chronic diseases, such as type 2 diabetes.2 However, the long-term cardiovascular effects of low-carb diets are not well studied, and there is significant heterogeneity among these diets.
Low-carb vs low-fat. Multiple meta-analyses comparing low-carb diets to low-fat diets have found that those following low-carb diets have significantly higher total cholesterol and LDL levels.3,4,5 The National Lipid Association’s review of evidence determined that LDL and total cholesterol responses vary in individuals following a low-carb diet, but that increasing LDL levels in particular were concerning enough to warrant lipid monitoring of patients on low-carb diets.6 Another meta-analysis evaluated the difference in estimated atherosclerotic cardiovascular disease (ASCVD) risk between low-carb and low-fat diets, finding those following a low-carb diet to have a lower estimated ASCVD risk but higher LDL levels.7
Weighing the benefits and harms. Since our patient’s dramatic weight loss and greatly increased exercise level would be expected to lower his LDL levels, the severe worsening of his LDL levels was likely related to his ketogenic diet and was a factor in the early onset of CAD. The benefits of low-carb diets for weight loss, contrasted with the consistent worsening of LDL levels, has prompted a debate about which parameters should be considered in estimating the long-term risk of these diets for patients. Diamond et al8 posit that these diets have beneficial effects on “the most reliable [cardiovascular disease] risk factors,” but long-term, patient-oriented outcome data are lacking, and these diets may not be appropriate for certain patients, as our case demonstrates.
A reasonable strategy for patients contemplating a low-carb diet specifically for weight loss would be to use such a diet for 3 to 6 months to achieve initial and rapid results, then continue with a heart-healthy diet and increased exercise levels to maintain weight loss and reduce long-term cardiovascular risk.
Our patient was started on a postoperative medication regimen of aspirin 81 mg/d, evolocumab 140 mg every 14 days, metoprolol tartrate 25 mg bid, and rosuvastatin 10 mg/d. A year later, he was able to resume a high level of physical activity (6-mile runs) without chest pain. His follow-up lipid panel showed a total cholesterol of 153 mg/dL; LDL, 53 mg/dL; HDL, 89 mg/dL; and triglycerides, 55 mg/dL. He had also switched to a regular diet and had been able to maintain his weight loss.
THE TAKEAWAY
Growing evidence suggests that low-carb diets may have a significant and detrimental effect on LDL levels. The long-term safety of these diets hasn’t been well studied, particularly regarding cardiovascular outcomes. At a minimum, patients who initiate low-carb diets should be counseled on general dietary recommendations regarding saturated fat and cholesterol intake, and they should have a follow-up lipid screening to evaluate for any significant worsening in total cholesterol and LDL levels.
CORRESPONDENCE
Samuel Dickmann, MD, 13611 NW 1st Lane, Suite 200, Newberry, FL 32669; [email protected]
1. Gorin A. What is the keto diet – and is it right for you? NBC News BETTER. February 22, 2018. Accessed February 3, 2023. www.nbcnews.com/better/health/what-keto-diet-it-right-you-ncna847256
2. Tinguely D, Gross J, Kosinski, C. Efficacy of ketogenic diets on type 2 diabetes: a systematic review. Current Diabetes Reports. 2021;21:32. doi: 10.1007/s11892-021-01399-z
3. Mansoor N, Vinknes KJ, Veierod MB, et al. Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors a meta-analysis of randomised controlled trials. Br J Nutr. 2016;115:466-479. doi: 10.1017/S0007114515004699
4. Bueno NB, de Melo ISV, de Oliveira SL, et al. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110:1178-1187. doi: 10.1017/S0007114513000548
5. Chawla S, Tessarolo Silva F, Amaral Medeiros S, et al. The effect of low-fat and low-carbohydrate diets on weight loss and lipid levels: a systematic review and meta-analysis. Nutrients. 2020;12:3774. doi: 10.3390/nu12123774
6. Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: a scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. J Clin Lipidol. 2019;13:689-711.e1. doi: 10.1016/j.jacl.2019.08.003
7. Sackner-Bernstein J, Kanter D, Kaul S. Dietary intervention for overweight and obese adults: comparison of low-carbohydrate and low-fat diets. a meta-analysis. PLoS One. 2015;10:e0139817. doi: 10.1371/journal.pone.0139817
8. Diamond DM, O’Neill BJ, Volek JS. Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified? Curr Opin Endocrinol Diabetes Obes. 2020;27:291-300. doi: 10.1097/MED.0000000000000568
1. Gorin A. What is the keto diet – and is it right for you? NBC News BETTER. February 22, 2018. Accessed February 3, 2023. www.nbcnews.com/better/health/what-keto-diet-it-right-you-ncna847256
2. Tinguely D, Gross J, Kosinski, C. Efficacy of ketogenic diets on type 2 diabetes: a systematic review. Current Diabetes Reports. 2021;21:32. doi: 10.1007/s11892-021-01399-z
3. Mansoor N, Vinknes KJ, Veierod MB, et al. Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors a meta-analysis of randomised controlled trials. Br J Nutr. 2016;115:466-479. doi: 10.1017/S0007114515004699
4. Bueno NB, de Melo ISV, de Oliveira SL, et al. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110:1178-1187. doi: 10.1017/S0007114513000548
5. Chawla S, Tessarolo Silva F, Amaral Medeiros S, et al. The effect of low-fat and low-carbohydrate diets on weight loss and lipid levels: a systematic review and meta-analysis. Nutrients. 2020;12:3774. doi: 10.3390/nu12123774
6. Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: a scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. J Clin Lipidol. 2019;13:689-711.e1. doi: 10.1016/j.jacl.2019.08.003
7. Sackner-Bernstein J, Kanter D, Kaul S. Dietary intervention for overweight and obese adults: comparison of low-carbohydrate and low-fat diets. a meta-analysis. PLoS One. 2015;10:e0139817. doi: 10.1371/journal.pone.0139817
8. Diamond DM, O’Neill BJ, Volek JS. Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified? Curr Opin Endocrinol Diabetes Obes. 2020;27:291-300. doi: 10.1097/MED.0000000000000568
Long-term BP reductions with renal denervation not race specific
WASHINGTON – On the heels the recently published final report from the SYMPLICITY HTN-3 renal denervation trial, a new analysis showed that Black patients, like non-Blacks, had sustained blood pressure control.
Contrary to a signal from earlier results, “there is nothing race specific about renal denervation,” said presenter Deepak L. Bhatt, MD, at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.
Black patients are well represented among patients with treatment-resistant hypertension and considered an important subgroup to target, according to Dr. Bhatt, director of Mount Sinai Heart, New York. This is the reason that they were not only a prespecified subgroup in SYMPLICITY HTN-3, but race was one of two stratification factors at enrollment. At the time of the study design, there was an expectation that Black patients would benefit more than non-Blacks.
This did not prove to be the case during the 6-month controlled phase of the trial. When patients randomized to renal denervation or the sham procedure were stratified by race, the primary endpoint of reduction in office systolic blood pressure (SBP) reached significance in the experimental arm among non-Black patients (–6.63 mm Hg; P = .01), but not among Black patients (–2.25 mm Hg; P = .09).
Blacks comprised 26% of SYMPLICITY HTN-3 trial
In the initial controlled analysis, published in the New England Journal of Medicine, the lack of benefit in the substantial Black enrollment – representing 26% of the study total – weighed against the ability of the trial to demonstrate a benefit, but Dr. Bhatt pointed out that BP reductions were unexpectedly high in the sham group regardless of race. Patients randomized to the sham group were encouraged to adhere to antihypertensive therapy, and based on response, this was particularly effective in the Black sham subgroup.
In SYMPLICITY HTN-3, patients with treatment-resistant hypertension were randomized to renal denervation or a sham procedure in a 2:1 ratio. While the controlled phase lasted just 6 months, the follow-up after the study was unblinded has continued out to 3 years. Safety and efficacy were assessed at 12, 24, and 36 months.
Unlike the disappointing results at 6 months, renal denervation has been consistently associated with significantly lower BP over long-term follow-up, even though those randomized to the sham procedure were permitted to cross over. About two-thirds of the sham group did so.
In the recently published final report of SYMPLICITY, the overall median change in office SBP at 3 years regardless of race was –26.4 mm Hg in the group initially randomized to renal denervation versus –5.7 mm Hg (P < .0001) among those randomized to the sham procedure.
In the subgroup analysis presented by Dr. Bhatt, the relative control of office SBP, as well as other measures of blood pressure, were similarly and significantly reduced in both Black and non-Black patients. In general, the relative control offered by being randomized initially to renal denervation increased over time in both groups.
For example, the relative reduction in office SBP favoring renal denervation climbed from –12.0 mm Hg at 12 months (P = .0066) to –21.0 at 18 months (P = .0002) and then to –24.9 mm Hg (P < .0001) at 36 months in the Black subgroup. In non-Blacks, the same type of relative reductions were seen at each time point, climbing from –13.5 (P < .0001) to –20.5 (P < .0001) and then to –21.0 (P < .0001).
The comparisons for other measures of BP control, including office diastolic BP, 24-hour SBP, and BP control during morning, day, and night periods were also statistically and similarly improved for those initially randomized to renal denervation rather than a sham procedure among both Blacks and non-Blacks.
Renal denervation safe in Black and non-Black patients
Renal denervation was well tolerated in both Black and non-Black participants with no signal of long-term risks over 36 months in either group. Among Blacks, rates of death at 36 months (3% vs. 11%) and stroke (7% vs. 11%) were lower among those randomized to renal denervation relative to sham patients who never crossed over, but Dr. Bhatt said the numbers are too small to draw any conclusions about outcomes.
While this subgroup analysis, along with the final SYMPLICITY report, supports the efficacy of renal denervation over the long term, these data are also consistent with the recently published analysis of SPYRAL ON-MED . Together, these data have led many experts, including Dr. Bhatt, to conclude that renal denervation is effective and deserves regulatory approval.
“In out-of-control blood pressure, when patients have maxed out on medications and lifestyle, I think renal denervation is efficacious, and it is equally efficacious in Blacks and non-Blacks,” Dr. Bhatt said.
This subgroup analysis is important because of the need for options in treatment-resistant hypertension among Black as well as non-Black patients, pointed out Sripal Bangalore, MBBS, director of complex coronary intervention at New York University.
“I am glad that we did not conclude too soon that it does not work in Blacks,” Dr. Bangalore said. If renal denervation is approved, he expects this procedure to be a valuable tool in this racial group.
Dr. Bhatt reported financial relationship with more than 20 pharmaceutical and device companies, including Medtronic, which provided funding for the SYMPLICITY HTN-3 trial. Dr. Bangalore has financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic.
WASHINGTON – On the heels the recently published final report from the SYMPLICITY HTN-3 renal denervation trial, a new analysis showed that Black patients, like non-Blacks, had sustained blood pressure control.
Contrary to a signal from earlier results, “there is nothing race specific about renal denervation,” said presenter Deepak L. Bhatt, MD, at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.
Black patients are well represented among patients with treatment-resistant hypertension and considered an important subgroup to target, according to Dr. Bhatt, director of Mount Sinai Heart, New York. This is the reason that they were not only a prespecified subgroup in SYMPLICITY HTN-3, but race was one of two stratification factors at enrollment. At the time of the study design, there was an expectation that Black patients would benefit more than non-Blacks.
This did not prove to be the case during the 6-month controlled phase of the trial. When patients randomized to renal denervation or the sham procedure were stratified by race, the primary endpoint of reduction in office systolic blood pressure (SBP) reached significance in the experimental arm among non-Black patients (–6.63 mm Hg; P = .01), but not among Black patients (–2.25 mm Hg; P = .09).
Blacks comprised 26% of SYMPLICITY HTN-3 trial
In the initial controlled analysis, published in the New England Journal of Medicine, the lack of benefit in the substantial Black enrollment – representing 26% of the study total – weighed against the ability of the trial to demonstrate a benefit, but Dr. Bhatt pointed out that BP reductions were unexpectedly high in the sham group regardless of race. Patients randomized to the sham group were encouraged to adhere to antihypertensive therapy, and based on response, this was particularly effective in the Black sham subgroup.
In SYMPLICITY HTN-3, patients with treatment-resistant hypertension were randomized to renal denervation or a sham procedure in a 2:1 ratio. While the controlled phase lasted just 6 months, the follow-up after the study was unblinded has continued out to 3 years. Safety and efficacy were assessed at 12, 24, and 36 months.
Unlike the disappointing results at 6 months, renal denervation has been consistently associated with significantly lower BP over long-term follow-up, even though those randomized to the sham procedure were permitted to cross over. About two-thirds of the sham group did so.
In the recently published final report of SYMPLICITY, the overall median change in office SBP at 3 years regardless of race was –26.4 mm Hg in the group initially randomized to renal denervation versus –5.7 mm Hg (P < .0001) among those randomized to the sham procedure.
In the subgroup analysis presented by Dr. Bhatt, the relative control of office SBP, as well as other measures of blood pressure, were similarly and significantly reduced in both Black and non-Black patients. In general, the relative control offered by being randomized initially to renal denervation increased over time in both groups.
For example, the relative reduction in office SBP favoring renal denervation climbed from –12.0 mm Hg at 12 months (P = .0066) to –21.0 at 18 months (P = .0002) and then to –24.9 mm Hg (P < .0001) at 36 months in the Black subgroup. In non-Blacks, the same type of relative reductions were seen at each time point, climbing from –13.5 (P < .0001) to –20.5 (P < .0001) and then to –21.0 (P < .0001).
The comparisons for other measures of BP control, including office diastolic BP, 24-hour SBP, and BP control during morning, day, and night periods were also statistically and similarly improved for those initially randomized to renal denervation rather than a sham procedure among both Blacks and non-Blacks.
Renal denervation safe in Black and non-Black patients
Renal denervation was well tolerated in both Black and non-Black participants with no signal of long-term risks over 36 months in either group. Among Blacks, rates of death at 36 months (3% vs. 11%) and stroke (7% vs. 11%) were lower among those randomized to renal denervation relative to sham patients who never crossed over, but Dr. Bhatt said the numbers are too small to draw any conclusions about outcomes.
While this subgroup analysis, along with the final SYMPLICITY report, supports the efficacy of renal denervation over the long term, these data are also consistent with the recently published analysis of SPYRAL ON-MED . Together, these data have led many experts, including Dr. Bhatt, to conclude that renal denervation is effective and deserves regulatory approval.
“In out-of-control blood pressure, when patients have maxed out on medications and lifestyle, I think renal denervation is efficacious, and it is equally efficacious in Blacks and non-Blacks,” Dr. Bhatt said.
This subgroup analysis is important because of the need for options in treatment-resistant hypertension among Black as well as non-Black patients, pointed out Sripal Bangalore, MBBS, director of complex coronary intervention at New York University.
“I am glad that we did not conclude too soon that it does not work in Blacks,” Dr. Bangalore said. If renal denervation is approved, he expects this procedure to be a valuable tool in this racial group.
Dr. Bhatt reported financial relationship with more than 20 pharmaceutical and device companies, including Medtronic, which provided funding for the SYMPLICITY HTN-3 trial. Dr. Bangalore has financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic.
WASHINGTON – On the heels the recently published final report from the SYMPLICITY HTN-3 renal denervation trial, a new analysis showed that Black patients, like non-Blacks, had sustained blood pressure control.
Contrary to a signal from earlier results, “there is nothing race specific about renal denervation,” said presenter Deepak L. Bhatt, MD, at the Cardiovascular Research Technologies conference, sponsored by MedStar Heart & Vascular Institute.
Black patients are well represented among patients with treatment-resistant hypertension and considered an important subgroup to target, according to Dr. Bhatt, director of Mount Sinai Heart, New York. This is the reason that they were not only a prespecified subgroup in SYMPLICITY HTN-3, but race was one of two stratification factors at enrollment. At the time of the study design, there was an expectation that Black patients would benefit more than non-Blacks.
This did not prove to be the case during the 6-month controlled phase of the trial. When patients randomized to renal denervation or the sham procedure were stratified by race, the primary endpoint of reduction in office systolic blood pressure (SBP) reached significance in the experimental arm among non-Black patients (–6.63 mm Hg; P = .01), but not among Black patients (–2.25 mm Hg; P = .09).
Blacks comprised 26% of SYMPLICITY HTN-3 trial
In the initial controlled analysis, published in the New England Journal of Medicine, the lack of benefit in the substantial Black enrollment – representing 26% of the study total – weighed against the ability of the trial to demonstrate a benefit, but Dr. Bhatt pointed out that BP reductions were unexpectedly high in the sham group regardless of race. Patients randomized to the sham group were encouraged to adhere to antihypertensive therapy, and based on response, this was particularly effective in the Black sham subgroup.
In SYMPLICITY HTN-3, patients with treatment-resistant hypertension were randomized to renal denervation or a sham procedure in a 2:1 ratio. While the controlled phase lasted just 6 months, the follow-up after the study was unblinded has continued out to 3 years. Safety and efficacy were assessed at 12, 24, and 36 months.
Unlike the disappointing results at 6 months, renal denervation has been consistently associated with significantly lower BP over long-term follow-up, even though those randomized to the sham procedure were permitted to cross over. About two-thirds of the sham group did so.
In the recently published final report of SYMPLICITY, the overall median change in office SBP at 3 years regardless of race was –26.4 mm Hg in the group initially randomized to renal denervation versus –5.7 mm Hg (P < .0001) among those randomized to the sham procedure.
In the subgroup analysis presented by Dr. Bhatt, the relative control of office SBP, as well as other measures of blood pressure, were similarly and significantly reduced in both Black and non-Black patients. In general, the relative control offered by being randomized initially to renal denervation increased over time in both groups.
For example, the relative reduction in office SBP favoring renal denervation climbed from –12.0 mm Hg at 12 months (P = .0066) to –21.0 at 18 months (P = .0002) and then to –24.9 mm Hg (P < .0001) at 36 months in the Black subgroup. In non-Blacks, the same type of relative reductions were seen at each time point, climbing from –13.5 (P < .0001) to –20.5 (P < .0001) and then to –21.0 (P < .0001).
The comparisons for other measures of BP control, including office diastolic BP, 24-hour SBP, and BP control during morning, day, and night periods were also statistically and similarly improved for those initially randomized to renal denervation rather than a sham procedure among both Blacks and non-Blacks.
Renal denervation safe in Black and non-Black patients
Renal denervation was well tolerated in both Black and non-Black participants with no signal of long-term risks over 36 months in either group. Among Blacks, rates of death at 36 months (3% vs. 11%) and stroke (7% vs. 11%) were lower among those randomized to renal denervation relative to sham patients who never crossed over, but Dr. Bhatt said the numbers are too small to draw any conclusions about outcomes.
While this subgroup analysis, along with the final SYMPLICITY report, supports the efficacy of renal denervation over the long term, these data are also consistent with the recently published analysis of SPYRAL ON-MED . Together, these data have led many experts, including Dr. Bhatt, to conclude that renal denervation is effective and deserves regulatory approval.
“In out-of-control blood pressure, when patients have maxed out on medications and lifestyle, I think renal denervation is efficacious, and it is equally efficacious in Blacks and non-Blacks,” Dr. Bhatt said.
This subgroup analysis is important because of the need for options in treatment-resistant hypertension among Black as well as non-Black patients, pointed out Sripal Bangalore, MBBS, director of complex coronary intervention at New York University.
“I am glad that we did not conclude too soon that it does not work in Blacks,” Dr. Bangalore said. If renal denervation is approved, he expects this procedure to be a valuable tool in this racial group.
Dr. Bhatt reported financial relationship with more than 20 pharmaceutical and device companies, including Medtronic, which provided funding for the SYMPLICITY HTN-3 trial. Dr. Bangalore has financial relationships with Abbott Vascular, Amgen, Biotronik, Inari, Pfizer, Reata, and Truvic.
AT CRT 2023
COORDINATEd effort boosts optimal therapy in patients with T2D and ASCVD
NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.
Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.
“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.
The goal is getting patients on triple therapy
The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.
Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.
Simultaneously with her report, the findings also appeared online in JAMA.
At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.
At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.
Effective interventions and the need for a champion
The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:
- Analysis of the barriers to evidence-based care at each clinic.
- Development of local interdisciplinary care pathways to address the identified barriers.
- Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
- Education of the clinic staff, including provision of educational materials.
- Auditing of clinic performance using specified metrics and feedback on the findings.
Clinics in the usual care group were given current clinical practice guidelines.
The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.
Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.
“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.
Research advances often don’t translate into management changes
“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.
“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.
“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”
The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.
The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.
COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.
NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.
Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.
“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.
The goal is getting patients on triple therapy
The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.
Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.
Simultaneously with her report, the findings also appeared online in JAMA.
At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.
At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.
Effective interventions and the need for a champion
The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:
- Analysis of the barriers to evidence-based care at each clinic.
- Development of local interdisciplinary care pathways to address the identified barriers.
- Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
- Education of the clinic staff, including provision of educational materials.
- Auditing of clinic performance using specified metrics and feedback on the findings.
Clinics in the usual care group were given current clinical practice guidelines.
The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.
Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.
“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.
Research advances often don’t translate into management changes
“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.
“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.
“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”
The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.
The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.
COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.
NEW ORLEANS – Twenty cardiology clinics successfully intensified the medical care they gave patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) after receiving a simple and scalable investigational intervention that gave the clinics’ staffs guidance on best prescribing practices and implementation and also provided quality-improvement feedback.
Within a year, these clinics quadrupled optimal medical management of these patients, compared with control clinics, in a randomized trial involving a total of 43 clinics and 1,049 patients.
“This multifaceted intervention is effective in increasing the prescription of evidence-based therapies in adults with T2D and ASCVD,” Neha J. Pagidipati, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“The next step is to scale this intervention across cardiology practices” interested in improving the quality of care they deliver to these patients, added Dr. Pagidipati, a cardiologist specializing in cardiometabolic disease prevention at Duke University in Durham, N.C.
The goal is getting patients on triple therapy
The primary outcome of the COORDINATE-Diabetes trial was the change in the number of patients with T2D and ASCVD who received prescriptions for agents from three recommended medication classes and at recommended dosages: a high-intensity statin, a renin-angiotensin system inhibitor (RASi), and at least one agent from either of two classes that have both cardiovascular-protective and antihyperglycemic effects: the sodium-glucose cotransporter 2 (SGLT2) inhibitors, or the glucagonlike peptide 1 (GLP-1)–receptor agonists.
Among the 457 patients treated at the 20 cardiology clinics who received the quality-improvement intervention, 37.9% were on the promoted triple therapy after 12 months, compared with 14.5% of the 588 patients treated at the 23 clinics that continued with their usual care approach. This 23.4–percentage point increase in triple-class prescribing at recommended dosages represented a significant 4.4-fold increase in the goal prescribing endpoint after adjustment for possible confounders, Dr. Pagidipati reported.
Simultaneously with her report, the findings also appeared online in JAMA.
At baseline, 41%-50% of the patients were on both a high-intensity statin and a RASi, with a total of about 58%-67% on a high-intensity statin and about 70%-75% on a RASi. Fewer than 1% of patients were on SGLT2 inhibitors or GLP-1–receptor agonists at baseline. By design, no patient could be on all three categories of medication at baseline.
At their last follow-up visit (after 12 months for 97% of patients, or after 6 months for the remainder) 71% of the patients at practices that received the intervention were on a high-intensity statin, 81% were taking a RASi, and 60% were on an SGLT2 inhibitor or GLP-1–receptor agonist. Among the control patients, 58% were on a high-intensity statin, 68% on a RASi, and 36% were on one of the antihyperglycemic agents.
Effective interventions and the need for a champion
The clinics randomized to the active arm received instruction from a three-member team, either from an in-person or virtual one-time visit, on an intervention comprising several initiatives:
- Analysis of the barriers to evidence-based care at each clinic.
- Development of local interdisciplinary care pathways to address the identified barriers.
- Facilitation of care coordination among clinicians – particularly among cardiology, endocrinology, and primary care clinicians.
- Education of the clinic staff, including provision of educational materials.
- Auditing of clinic performance using specified metrics and feedback on the findings.
Clinics in the usual care group were given current clinical practice guidelines.
The investigational intervention was, by design, “low-tech and designed to be scalable,” explained Dr. Pagidipati, and once the COVID pandemic started the intervention team shifted to a virtual consultation with participating practices that was mostly front-loaded, followed by monthly phone calls to give clinics feedback on their progress.
Among the most helpful aspects of the intervention was involving the entire clinic staff, including pharmacists, nurses, and advanced care practitioners; boosting familiarity with the relevant medications and their appropriate use; and advice on navigating insurance-coverage barriers such as prior authorizations.
“What was most critical was having a local champion who took on making this effort an important part” of what the clinic was trying to do, she explained. “All it takes is passion, and the tenacity of a bulldog,” Dr. Pagidipati said.
Research advances often don’t translate into management changes
“We don’t do a great job of translating findings from trials to patient care, so any method we can use to improve that will improve practice,” commented Kristen B. Campbell, PharmD, a clinical pharmacist at Duke who was not involved in the study.
“Although the trial was not powered to look at patient outcomes, we think that patients will benefit” because all the recommended medication uses have been proven to help patients in prior trials, Dr. Campbell noted.
“A particular strength of this study was its simple design. All the interventions are low-tech and scalable.”
The low level of use of guideline-directed medical therapy in American adults with type 2 diabetes and atherosclerotic cardiovascular disease is “incredible,” said Christopher B. Granger, MD, a senior investigator on the study and a cardiologist and professor at Duke.
The researchers who ran the study are now focused on evaluating which cardiology clinics and patients had the most success from the intervention and are using that information to further refine implementation. They are also planning to encourage cardiology practices as well as other relevant medical groups to incorporate the intervention and implementation model used in the trial. The intervention program is detailed and available at no charge on the COORDINATE-Diabetes website.
COORDINATE-Diabetes received funding from Boehringer Ingelheim and Eli Lilly. Dr. Pagidipati has received personal fees from Boehringer Ingelheim, Lilly, AstraZeneca, Novartis, Novo Nordisk, Merck, and CRISPR Therapeutics, and she has received research grants from Amgen, Novartis, Novo Nordisk, and Eggland’s Best. Dr. Campbell had no disclosures. Dr. Granger has received personal fees and research funding from numerous companies.
AT ACC 2023
Med center and top cardio surgeon must pay $8.5 million for fraud, concurrent surgeries
the Department of Justice (DOJ) announced.
The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.
Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.
In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.
The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.
The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.
Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”
“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.
“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.
Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.
Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.
Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.
The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.
For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.
“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”
A version of this article first appeared on Medscape.com.
the Department of Justice (DOJ) announced.
The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.
Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.
In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.
The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.
The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.
Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”
“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.
“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.
Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.
Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.
Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.
The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.
For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.
“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”
A version of this article first appeared on Medscape.com.
the Department of Justice (DOJ) announced.
The lawsuit alleges that James L. Luketich, MD, the longtime chair of the school’s cardiothoracic surgery department, regularly performed up to three complex surgical procedures simultaneously, moving among multiple operating rooms and attending to matters other than patient care. The investigation began after Jonathan D’Cunha, MD, a former UPMC surgeon, raised concerns about his colleague’s surgical scheduling and billing practices.
Dr. Luketich’s overbooking of procedures led to patients enduring hours of medically unnecessary anesthesia time and risking surgical complications, according to court documents.
In addition, the complaint states that these practices violated the False Claims Act, which prohibits “teaching physicians” like Dr. Luketich from billing Medicare and other government health plans for “concurrent surgeries” – regulations federal authorities say UPMC leadership were aware of and the University of Pittsburgh Physicians (UPP), also named in the suit, permitted Dr. Luketich to skirt.
The whistleblower provision of the False Claims Act allows private parties to file an action on behalf of the United States and receive a portion of the recovery to help deter health care fraud, says the DOJ.
The defendants previously asked the court to dismiss the case, but a judge denied the request in June 2022.
Paul Wood, vice president and chief communications officer for UPMC, told this news organization that the lawsuit pertained to Dr. Luketich’s “most complicated, team-based surgical procedures.”
“At issue was compliance with the Centers for Medicare & Medicaid Services’ (CMS’s) Teaching Physician Regulation and related billing guidance as well as with UPMC’s internal surgical policies,” he said.
“While UPMC continues to believe Dr. Luketich’s surgical practice complies with CMS requirements, it has agreed to [the settlement] to avoid the distraction and expense of further litigation,” said Mr. Wood, adding that all parties agree that UPMC can seek clarity from CMS regarding future billing of these surgeries.
Efrem Grail, JD, Dr. Luketich’s attorney, said in an interview that he and Dr. Luketich are pleased that the settlement puts an end to the case and that he hopes the United States will issue “authoritative guidance” on billing regulations for teaching physicians, something medical schools and hospitals have sought for years.
Dr. Luketich, UPMC, and UPP face more legal challenges from a separate medical malpractice lawsuit. In March 2018, Bernadette Fedorka underwent a lung transplant at UPMC. Although Dr. Luketich did not perform the surgery, Ms. Fedorka alleges that his poor leadership caused understaffing of the lung transplant program and contributed to surgical complications, including a 4-inch piece of wire left in her neck.
Ms. Fedorka claims that suboxone impaired Dr. Luketich’s decision-making. He began taking the drug in 2008 to manage the pain from a slipped disc injury after a history of prescription drug abuse. Both UPMC and Dr. Luketich have denied the validity of Ms. Fedorka’s claims.
The malpractice suit centers on a recording of a conversation between Dr. Luketich and David Wilson, MD, who prescribed the suboxone and treated the surgeon’s opioid use disorder for several years. Dr. Luketich has accused former colleagues, Dr. D’Cunha and Lara Schaheen, MD, of illegally recording the private conversation that discussed Dr. Luketich’s suboxone prescription – something both physicians deny.
For the billing fraud case, Dr. Luketich has agreed to complete a corrective action plan and submit to a third-party audit of his Medicare billings for 1 year.
“This is an important settlement and a just conclusion to the United States’ investigation into Dr. Luketich’s surgical and billing practices and UPMC and UPP’s acceptance of those practices,” Acting U.S. Attorney Troy Rivetti said in a statement that, “no medical provider – however renowned – is excepted from scrutiny or above the law.”
A version of this article first appeared on Medscape.com.