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Macitentan produces similar results in PAH-SSc and IPAH/HPAH
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
NEW ORLEANS – Real-world data support the use of macitentan to treat pulmonary arterial hypertension (PAH) associated with connective tissue disease, according to a speaker at the annual meeting of the American College of Chest Physicians.
Outcomes of macitentan (Opsumit) treatment were similar in patients who had PAH associated with systemic sclerosis (PAH-SSc) and patients who had idiopathic PAH (IPAH) or heritable PAH (HPAH), Vallerie McLaughlin, MD, of the University of Michigan, Ann Arbor, said at the meeting.
“Within the limits of a real-world registry, these data add to the growing body of evidence supporting the use of macitentan for treatment in patients with CTD [connective tissue disease],” Dr. McLaughlin said.
She and her colleagues evaluated data from the prospective OPUS registry (NCT02126943) and the retrospective OrPHeUS study (NCT03197688), both of which included patients who were newly started on macitentan.
Dr. McLaughlin presented data on 2,311 patients with IPAH/HPAH and 668 patients with PAH-SSc. She also presented data on patients with PAH-systemic lupus erythematosus and PAH-mixed CTD, but numbers in these groups were small, and outcomes were similar to those in the PAH-SSc group.
Demographic and disease characteristics at the start of macitentan were similar between the IPAH/HPAH and PAH-SSc groups. The median age was 64 years in both groups. The median time from PAH diagnosis was 7.6 months in the IPAH/HPAH group and 8.5 months in the PAH-SSc group.
The median duration of macitentan exposure was 13.4 months in the IPAH/HPAH group and 14.4 months in the PAH-SSc group. The proportion of patients receiving macitentan in combination with other therapies (double or triple combinations) increased from baseline to 6 months in both groups.
Hepatic adverse events occurred in 7.4% of IPAH/HPAH patients and 7.9% of PAH-SSc patients. The most common adverse events among the IPAH/HPAH and PAH-SSc groups in the OPUS registry alone were dyspnea (19% and 26.1%, respectively), peripheral edema (9.8% and 12.4%), fatigue (6.8% and 11.7%), anemia (6.7% and 11.7%), headache (10.2% and 11%), and dizziness (6.7% and 10.7%).
About 39% of patients in both groups discontinued macitentan. Similar proportions in each group discontinued because of adverse events (17% in the IPAH/HPAH group and 18.3% in the PAH-SSc group) and hepatic adverse events (0.2% and 0.7%, respectively).
The proportion of patients with at least one hospitalization was 36.2% in the IPAH/HPAH group and 40.1% in the PAH-SSc group.
The 12-month Kaplan-Meier survival estimate was 92.9% in the IPAH/HPAH group and 91.3% in the PAH-SSc group. The 24-month estimated survival rate was 85.6% and 82.1%, respectively.
The OPUS registry and OrPHeUS study are sponsored by Actelion. Dr. McLaughlin disclosed relationships with Actelion, Acceleron, Bayer, Caremark, CiVi Biopharma, Reata, Sonovie, and United Therapeutics.
SOURCE: McLaughlin V et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.827.
REPORTING FROM CHEST 2019
One third of CVD disease in black adults linked to hypertension
A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.
The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.
Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.
The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.
At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.
In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.
Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.
After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.
“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.
Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.
The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.
SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.
A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.
The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.
Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.
The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.
At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.
In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.
Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.
After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.
“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.
Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.
The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.
SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.
A significant portion of the increased cardiovascular disease risk seen in black adults may stem from hypertension, according to a prospective cohort study published by a team led by Donald Clark III, MD, of the University of Mississippi in Jackson.
The analysis showed that about one-third of cardiovascular disease can be traced to hypertension in black adults, and the influence was much stronger in individuals under 60, suggesting that early interventions to maintain normal blood pressure have the potential to reduce risk in this population.
Hypertension is already known to be the leading contributor to cardiovascular disease (CVD) in the United States, and non-Hispanic black adults experience it at a rate of 55%, higher than any other group.
The researchers used data from the Jackson Heart Study (JHS) and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine the association between CVD and hypertension, and NHANES 2011-2014 to examine the rate of hypertension among non-Hispanic black adults in the United States.
At baseline, among 12,497 participants In the JHS and REGARDS studies, 33% had normal blood pressure, 41% had elevated BP, and 36% had hypertension. In the NHANES cohort, 35% had normal BP, 12% had elevated BP, and 53% had hypertension.
In the combined JHS and REGARDS cohorts, subjects with elevated BP and hypertension had greater odds of taking cholesterol-lowering medication compared to those with normal BP: 8.5% of normotensive patients and 9.9% of those with elevated BP were on medication, compared with 26.0% of hypertensive patient, emphasizing the importance of effective hypertension management, the investigators noted.
Similarly, 9.9% of patients with normal BP and 14.7% of those with elevated BP had diabetes, compared with 26.0% of hypertensive patients. Hypertensive patients were also less likely to have graduated from high school (81%) than were those with elevated BP (84.5%) and normal BP (89.9%), and they had a higher mean body mass index (31.4 kg/m2) than their counterparts with elevated (29.6) and normal (28.8) BP.
After a maximum of 14.3 years of follow-up, 9.9% of participants experienced a CVD event. The researchers calculated the population attributable risk (PAR) using the prevalence of hypertension from the NHANES dataset and the multivariable-adjusted association between elevated versus normal BP and hypertension versus normal BP in the JHS and REGARDS data.
“Hypertension was independently associated with incident [coronary heart disease], heart failure, and stroke,” the investigators wrote. The PARs associated with hypertension were 32.5% (95% CI, 20.5-43.6%) for CVD, 42.7% (95% CI, 24.0-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6-40.8%) for heart failure, and 38.9% (95% CI, 19.4-55.6%) for stroke.
Men and women had similar PAR values for CVD (33.9% vs. 31.1%). Participants younger than 60 had a higher value of PAR associated with hypertension than older participants (54.6% [95% CI, 37.2-68.7%] vs. 32.0% [95% CI, 11.9-48.1%]). Dr. Clark and his coinvestigators noted that the “most substantial finding” of the study was PAR of 69% for stroke associated with hypertension found in patients younger than 60 years. “These data suggest that interventions to maintain normal BP across the life course may reduce the incidence of CVD in this population,” they concluded.
The REGARDS study was funded by NIH and the American Heart Association. The JHS study was funded by Jackson State University, Tougaloo College, the Mississippi State Department of Health, and the University of Mississippi Medical Center. The authors have extensive financial ties to pharmaceutical companies.
SOURCE: JAMA Card. 2019. October 23, 2019. doi:10.1001/jamacardio.2019.3773.
FROM JAMA CARDIOLOGY
Macitentan, tadalafil combo found effective for newly diagnosed PAH
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
NEW ORLEANS – Treatment with macitentan and tadalafil can elicit improvements in patients with newly diagnosed pulmonary arterial hypertension (PAH), trial results suggest.
In the phase 4 OPTIMA trial, the combination significantly improved cardiopulmonary hemodynamics, functional class, 6-minute walk distance, and N-terminal pro B-type natriuretic peptide (NT-proBNP).
Olivier Sitbon, MD, PhD, of Université Paris–Sud in France, presented these results at the annual meeting of the American College of Chest Physicians.
The OPTIMA trial (NCT02968901) enrolled 46 adults who were newly diagnosed with PAH and had medium functional ability (WHO functional class II-III). The patients’ mean age was 57.4 ± 14.9 years, and 65% of them were female.
The mean time from PAH diagnosis was 29.6 ± 55.2 days. Patients had idiopathic PAH (63%), PAH associated with connective tissue disease (19.6%), heritable PAH (6.5%), drug- or toxin-induced PAH (4.4%), HIV-associated PAH (2.2%), and “other” PAH (4.4%).
Patients initially received macitentan at 10 mg once daily and tadalafil at 20 mg once daily. After 8 ± 3 days, the tadalafil dose was increased to 40 mg once daily. The median duration of treatment was 19.9 months.
The researchers assessed efficacy at week 16, but patients were monitored for safety until the study was closed by the sponsor. There were 44 patients who remained on study through week 16, and 39 patients completed the study.
Results
The study’s primary endpoint was the change in pulmonary vascular resistance (PVR). The ratio of week 16 to baseline PVR was 0.53, which translates to a significant 47% reduction in PVR. In fact, 87% of patients had a 30% or greater decrease in PVR from baseline to week 16.
Patients had improvements in other endpoints as well. The mean cardiac index increased from 2.2 to 3.1 L/min/m2 (P less than .0001) from baseline to week 16. The mean pulmonary arterial pressure decreased from 50.0 to 42.2 mm Hg (P = .0002), and the mean right atrial pressure decreased from 8.1 to 7.8 mm Hg (P = .7321).
The mean mixed venous oxygen saturation increased from 63.0% to 68.2% (P = .0003). The mean total pulmonary resistance decreased from 1109.4 to 677.4 dynes/sec/cm-5 (P less than .0001).
NT-proBNP decreased 68% from baseline to week 16. The geometric mean ratio was 0.32 (P less than .0001). The 6-minute walk distance increased from 352.2 to 388.1 m (P = .0008).
None of the patients experienced a worsening of WHO functional class from baseline to week 16, and 63% of patients experienced an improvement.
Nearly 94% of patients (n = 43) had at least one adverse event, 28% (n = 13) had serious adverse events, and 6.5% (n = 3) stopped treatment because of adverse events. The most frequent events were peripheral edema (n = 13), headache (n = 11), diarrhea (n = 9), and dyspnea (n = 7).
Three patients died during follow-up, one due to multiorgan failure and two due to underlying disease.
Actelion Pharmaceuticals funded the trial. Dr. Sitbon disclosed relationships with Actelion, Bayer, GSK, Merck, Arena Pharmaceuticals, Gossamer Bio, and Ferrer.
SOURCE: Sitbon O et al. CHEST 2019. Abstract, doi: 10.1016/j.chest.2019.08.825.
REPORTING FROM CHEST 2019
Balloon pulmonary angioplasty beats riociguat in randomized CTEPH trial
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
MADRID – according to a multicenter trial presented at the annual congress of the European Respiratory Congress.
Both therapies are widely used in the treatment of CTEPH, but this is the first controlled trial in which they were directly compared, according to Xavier Jaïs, MD, of the Pulmonology Service, Kremlin-Bicêtre Hospital, University of Paris-Sud.
In this randomized trial, called RACE, newly diagnosed and previously untreated patients with nonoperable CTEPH were enrolled. The key eligibility criteria included PVR greater than 320 dynes/sec per cm–5 and a pulmonary capillary wedge pressure of 15 mm Hg or less.
The patients were randomized to BPA or riociguat and followed for 26 weeks. The primary endpoint was relative change in PVR from baseline. The 6-minute walk distance, change in functional class, time to clinical worsening and safety were among secondary endpoints.
As calculated by geometric mean from baseline, PVR was reduced by nearly 60% in the BPA group and by 32% in the riociguat group, providing a 40% (P less than .0001) relative advantage of BPA.
Although there was a small relative advantage in the 6-minute walk distance for the BPA group at the end of the study, it did not reach statistical significant. However, 88% of those randomized to BPA versus 49% of those treated with riociguat (P less than .0001) improved by at least one WHO class by the end of the study.
Clinical worsening events over the course of the trial were uncommon. All three of these events occurred in the riociguat group, but the difference was not significant.
The end-of-study reduction in brain natriuretic peptide, which was another secondary endpoint, was 67% greater in the BPA group (P less than .0001).
There was a safety cost for the greater efficacy of BPA. This included a higher proportion of patients in the BPA group with at least one serious adverse event (50% vs. 26%) and at least one serious treatment-related adverse event (14% vs. 9%). No patient in either arm discontinued therapy because of treatment-related adverse events, and there were no deaths over the course of the study in either arm.
The study has included a 6-month extension to allow patients symptomatic on their originally assigned therapy to switch to the opposite treatment. Results of the extension are not yet available, but Dr. Jaïs said that these data might provide insight about which therapy to start first.
“It was very important to do this trial,” according to the ERS-invited discussant, Martin Kolb, MD, of the Firestone Institute of Respiratory Health, McMaster University, Hamilton, Ont. The most recent World Symposium on Pulmonary Hypertension identified BPA and medical therapy as reasonable choices in inoperable CTEPH, but Dr. Kolb said there has been an unmet need for comparative data.
“This was a very strong study that demonstrated a powerful impact for both interventions on pulmonary vascular resistance,” Dr. Kolb said, adding that, although BPA proved to be more effective, clinicians consider the greater risk of adverse events. He believes further work needs to be done in identifying the best candidates for each and to explore hybrid approaches.
“What do you think about doing these sequentially so that you lower the pressure first with medical therapy and then go in with the balloon?” Dr. Kolb asked Dr. Jaïs during a discussion that followed presentation of the RACE results.
Dr. Jaïs conceded this point, noting that the treatments have different targets and might be complementary.
“We plan to do a study like this in the future,” Dr. Jaïs said.
Dr. Jaïs reported no potential conflicts of interest.
REPORTING FROM ERS 2019
Ibrutinib linked to hypertension in B-cell malignancies
The incidence and severity of hypertension was considerably higher in patients with B-cell malignancies treated with ibrutinib, according to a retrospective analysis.
Additionally, new or worsening hypertension was associated with a greater risk of major adverse cardiac events (MACE), including stroke, myocardial infarction, and cardiovascular-related death (hazard ratio, 2.17; 95% confidence interval, 1.08-4.38; P = .03).
“Despite ibrutinib’s benefits, cardiotoxicity has emerged as an increasingly important complication of this life-saving therapy,” Tyler Dickerson, PhD, of the Ohio State University, Columbus, and colleagues wrote in Blood.
The researchers retrospectively studied 562 consecutive patients with a lymphoid malignancy who received ibrutinib. Data was collected from patients treated at The Ohio State University’s Comprehensive Cancer Center during 2009-2016.
The mean age of study participants was 63.8 years, with a mean body mass index of 28.0 kg/m2. Most of the patients included in the analysis were men.
The team assessed rates of new or worsening hypertension, as well as rates of other MACE. The observed rates were compared with Framingham Heart Study–predicted incident-hypertension rates. The effects of various antihypertensive drugs on ibrutinib-linked hypertension were also evaluated.
After a median follow-up of 30 months, 78.3% of patients who received ibrutinib had new or worsening hypertension using a systolic blood pressure cutoff of 130 mm Hg. Of these, 84.8% of cases had an “at least probable association with ibrutinib,” they reported.
Among the 215 patients with no baseline hypertension, 71.6% developed hypertension while on ibrutinib, with a mean increase in systolic blood pressure of 13.4 mm Hg. Among the 347 patients with baseline hypertension, 82.4% experienced a worsening of their hypertension.
“This relationship remained even after accounting for ibrutinib dose, and was not attenuated by the use of any specific anti-hypertensive class,” the researchers wrote.
The researchers observed MACE among 93 patients. This included 84 patients with new or worsening hypertension and 9 patients with stable or no hypertension. Most MACE events were of at least probable ibrutinib association, the researchers reported.
Overall, the cumulative incidence of new hypertension at 1 year was 442 per 1,000 person-years in the current study. This value is 12.9-fold higher than the Framingham Heart Study risk–predicted rate of 34 per 1,000 person-years.
“Given the expected continued increase in ibrutinib use, further studies characterizing the mechanisms, treatment, and implications of [hypertension] during ibrutinib use are needed,” the researchers wrote.
The study was funded by the National Institutes of Health, the D. Warren Brown Family Foundation, the Four Winds Foundation, and the Connie Brown CLL Research Fund. The authors reported financial affiliations with Janssen, Pharmacyclics, and other companies.
SOURCE: Dickerson T et al. Blood. 2019 Oct 3. doi: 10.1182/blood.2019000840.
The incidence and severity of hypertension was considerably higher in patients with B-cell malignancies treated with ibrutinib, according to a retrospective analysis.
Additionally, new or worsening hypertension was associated with a greater risk of major adverse cardiac events (MACE), including stroke, myocardial infarction, and cardiovascular-related death (hazard ratio, 2.17; 95% confidence interval, 1.08-4.38; P = .03).
“Despite ibrutinib’s benefits, cardiotoxicity has emerged as an increasingly important complication of this life-saving therapy,” Tyler Dickerson, PhD, of the Ohio State University, Columbus, and colleagues wrote in Blood.
The researchers retrospectively studied 562 consecutive patients with a lymphoid malignancy who received ibrutinib. Data was collected from patients treated at The Ohio State University’s Comprehensive Cancer Center during 2009-2016.
The mean age of study participants was 63.8 years, with a mean body mass index of 28.0 kg/m2. Most of the patients included in the analysis were men.
The team assessed rates of new or worsening hypertension, as well as rates of other MACE. The observed rates were compared with Framingham Heart Study–predicted incident-hypertension rates. The effects of various antihypertensive drugs on ibrutinib-linked hypertension were also evaluated.
After a median follow-up of 30 months, 78.3% of patients who received ibrutinib had new or worsening hypertension using a systolic blood pressure cutoff of 130 mm Hg. Of these, 84.8% of cases had an “at least probable association with ibrutinib,” they reported.
Among the 215 patients with no baseline hypertension, 71.6% developed hypertension while on ibrutinib, with a mean increase in systolic blood pressure of 13.4 mm Hg. Among the 347 patients with baseline hypertension, 82.4% experienced a worsening of their hypertension.
“This relationship remained even after accounting for ibrutinib dose, and was not attenuated by the use of any specific anti-hypertensive class,” the researchers wrote.
The researchers observed MACE among 93 patients. This included 84 patients with new or worsening hypertension and 9 patients with stable or no hypertension. Most MACE events were of at least probable ibrutinib association, the researchers reported.
Overall, the cumulative incidence of new hypertension at 1 year was 442 per 1,000 person-years in the current study. This value is 12.9-fold higher than the Framingham Heart Study risk–predicted rate of 34 per 1,000 person-years.
“Given the expected continued increase in ibrutinib use, further studies characterizing the mechanisms, treatment, and implications of [hypertension] during ibrutinib use are needed,” the researchers wrote.
The study was funded by the National Institutes of Health, the D. Warren Brown Family Foundation, the Four Winds Foundation, and the Connie Brown CLL Research Fund. The authors reported financial affiliations with Janssen, Pharmacyclics, and other companies.
SOURCE: Dickerson T et al. Blood. 2019 Oct 3. doi: 10.1182/blood.2019000840.
The incidence and severity of hypertension was considerably higher in patients with B-cell malignancies treated with ibrutinib, according to a retrospective analysis.
Additionally, new or worsening hypertension was associated with a greater risk of major adverse cardiac events (MACE), including stroke, myocardial infarction, and cardiovascular-related death (hazard ratio, 2.17; 95% confidence interval, 1.08-4.38; P = .03).
“Despite ibrutinib’s benefits, cardiotoxicity has emerged as an increasingly important complication of this life-saving therapy,” Tyler Dickerson, PhD, of the Ohio State University, Columbus, and colleagues wrote in Blood.
The researchers retrospectively studied 562 consecutive patients with a lymphoid malignancy who received ibrutinib. Data was collected from patients treated at The Ohio State University’s Comprehensive Cancer Center during 2009-2016.
The mean age of study participants was 63.8 years, with a mean body mass index of 28.0 kg/m2. Most of the patients included in the analysis were men.
The team assessed rates of new or worsening hypertension, as well as rates of other MACE. The observed rates were compared with Framingham Heart Study–predicted incident-hypertension rates. The effects of various antihypertensive drugs on ibrutinib-linked hypertension were also evaluated.
After a median follow-up of 30 months, 78.3% of patients who received ibrutinib had new or worsening hypertension using a systolic blood pressure cutoff of 130 mm Hg. Of these, 84.8% of cases had an “at least probable association with ibrutinib,” they reported.
Among the 215 patients with no baseline hypertension, 71.6% developed hypertension while on ibrutinib, with a mean increase in systolic blood pressure of 13.4 mm Hg. Among the 347 patients with baseline hypertension, 82.4% experienced a worsening of their hypertension.
“This relationship remained even after accounting for ibrutinib dose, and was not attenuated by the use of any specific anti-hypertensive class,” the researchers wrote.
The researchers observed MACE among 93 patients. This included 84 patients with new or worsening hypertension and 9 patients with stable or no hypertension. Most MACE events were of at least probable ibrutinib association, the researchers reported.
Overall, the cumulative incidence of new hypertension at 1 year was 442 per 1,000 person-years in the current study. This value is 12.9-fold higher than the Framingham Heart Study risk–predicted rate of 34 per 1,000 person-years.
“Given the expected continued increase in ibrutinib use, further studies characterizing the mechanisms, treatment, and implications of [hypertension] during ibrutinib use are needed,” the researchers wrote.
The study was funded by the National Institutes of Health, the D. Warren Brown Family Foundation, the Four Winds Foundation, and the Connie Brown CLL Research Fund. The authors reported financial affiliations with Janssen, Pharmacyclics, and other companies.
SOURCE: Dickerson T et al. Blood. 2019 Oct 3. doi: 10.1182/blood.2019000840.
FROM BLOOD
BP screening nearly universal among Medicare enrollees
and just under 90% saw a physician during the year, according to new data released by the Centers for Medicare & Medicaid Services.
The latest edition of Medicare Beneficiaries at a Glance takes a look at some of the services provided in 2017, and BP checks were high on the list, with 96% of enrollees getting screened. BP was also prominent on another list featured in the Medicare snapshot for 2017, as hypertension was the most common chronic condition among beneficiaries with a prevalence of 58%, the CMS said.
A second glance at the report shows that 41% of enrollees had high cholesterol that year, making it the next-most common chronic condition, with arthritis third at 33%, the CMS said. Diabetes was fourth and heart disease was fifth, but rounding gives them the same prevalence of 27%.
and just under 90% saw a physician during the year, according to new data released by the Centers for Medicare & Medicaid Services.
The latest edition of Medicare Beneficiaries at a Glance takes a look at some of the services provided in 2017, and BP checks were high on the list, with 96% of enrollees getting screened. BP was also prominent on another list featured in the Medicare snapshot for 2017, as hypertension was the most common chronic condition among beneficiaries with a prevalence of 58%, the CMS said.
A second glance at the report shows that 41% of enrollees had high cholesterol that year, making it the next-most common chronic condition, with arthritis third at 33%, the CMS said. Diabetes was fourth and heart disease was fifth, but rounding gives them the same prevalence of 27%.
and just under 90% saw a physician during the year, according to new data released by the Centers for Medicare & Medicaid Services.
The latest edition of Medicare Beneficiaries at a Glance takes a look at some of the services provided in 2017, and BP checks were high on the list, with 96% of enrollees getting screened. BP was also prominent on another list featured in the Medicare snapshot for 2017, as hypertension was the most common chronic condition among beneficiaries with a prevalence of 58%, the CMS said.
A second glance at the report shows that 41% of enrollees had high cholesterol that year, making it the next-most common chronic condition, with arthritis third at 33%, the CMS said. Diabetes was fourth and heart disease was fifth, but rounding gives them the same prevalence of 27%.
Hyponatremia almost as common with spironolactone as chlorthalidone
NEW ORLEANS – .
The investigators reviewed hypertension patients whose treatment regimens included one diuretic. Forty on chlorthalidone developed hyponatremia – defined as a serum sodium below 133 mEq/L – across 1,322 prescriptions, for an incidence of 3.03%. There were 31 cases across 1,159 spironolactone prescriptions, an incidence of 2.67%.
Among 14 patients in a substudy who discontinued chlorthalidone after developing hyponatremia at a mean of about 2 weeks, six (43%) subsequently developed hyponatremia on spironolactone, also at an average of about 2 weeks.
The findings suggest that spironolactone is more likely than generally thought to cause hyponatremia, a potentially severe complication of diuretics, and that hyponatremia on chlorthalidone increases the risk, said lead investigator Faris Matanes, MD, a hypertension researcher at the university.
“We used to think” that hyponatremia on spironolactone was “very unlikely, but actually it’s not; the incidence is really close to chlorthalidone,” a well-known cause, and “if a patient develops hyponatremia on chlorthalidone, we should be more careful about giving them spironolactone,” he said.
Almost half the spironolactone cases were on 25 mg/day or less, and over a quarter of the chlorthalidone cases were on 12.5 mg/day. Of the 154 hyponatremia cases across 10,660 hydrochlorothiazide prescriptions (1.44%), over a third were taking 12.5 mg/day or less.
Overall, hyponatremia was diagnosed at a mean of 40.4 days, but sometimes after 2 or more months of treatment.
The findings “mean that even if we start patients on a low dose, we can’t stop checking after one or two normal sodium levels.” Measurements need to be ongoing, Dr. Matanes said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
He and his team wanted to get around the limitations of previous diuretic hyponatremia studies, including use of more than one diuretic, markedly poor kidney function, and other confounders. To that end, the study was limited to outpatients on a single diuretic who had normal sodium levels both before and after their hyponatremic episode, and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m2. Exclusion criteria included heart failure, cirrhosis, and adrenal insufficiency.
Older white people with lower baseline sodium and eGFR values were most at risk. Contrary to previous reports, hyponatremia wasn’t more likely in men.
The mean sodium level during an episode was 130.2 mEq/L; the majority of patients eventually normalized and continued treatment.
Subjects in the main study were a mean of 66 years old, about two-thirds were white, and about 60% were women. The baseline eGFR was 77.2 mL/min/1.73 m2, and baseline sodium level 135.8 mEq/L.
All but one of the 14 substudy patients were women. Those who became hyponatremic when switched to spironolactone were older (mean 74.2 versus 65.8 years), had lower baseline eGFRs (63.7 versus 69.7 mL/min/1.73 m2), and were more likely to be white, but the differences were not statistically significant.
There was no external funding, and the investigators didn’t have any industry disclosures.
SOURCE: Matanes F et al. Joint Hypertension 2019, Abstracts 187 and 174.
NEW ORLEANS – .
The investigators reviewed hypertension patients whose treatment regimens included one diuretic. Forty on chlorthalidone developed hyponatremia – defined as a serum sodium below 133 mEq/L – across 1,322 prescriptions, for an incidence of 3.03%. There were 31 cases across 1,159 spironolactone prescriptions, an incidence of 2.67%.
Among 14 patients in a substudy who discontinued chlorthalidone after developing hyponatremia at a mean of about 2 weeks, six (43%) subsequently developed hyponatremia on spironolactone, also at an average of about 2 weeks.
The findings suggest that spironolactone is more likely than generally thought to cause hyponatremia, a potentially severe complication of diuretics, and that hyponatremia on chlorthalidone increases the risk, said lead investigator Faris Matanes, MD, a hypertension researcher at the university.
“We used to think” that hyponatremia on spironolactone was “very unlikely, but actually it’s not; the incidence is really close to chlorthalidone,” a well-known cause, and “if a patient develops hyponatremia on chlorthalidone, we should be more careful about giving them spironolactone,” he said.
Almost half the spironolactone cases were on 25 mg/day or less, and over a quarter of the chlorthalidone cases were on 12.5 mg/day. Of the 154 hyponatremia cases across 10,660 hydrochlorothiazide prescriptions (1.44%), over a third were taking 12.5 mg/day or less.
Overall, hyponatremia was diagnosed at a mean of 40.4 days, but sometimes after 2 or more months of treatment.
The findings “mean that even if we start patients on a low dose, we can’t stop checking after one or two normal sodium levels.” Measurements need to be ongoing, Dr. Matanes said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
He and his team wanted to get around the limitations of previous diuretic hyponatremia studies, including use of more than one diuretic, markedly poor kidney function, and other confounders. To that end, the study was limited to outpatients on a single diuretic who had normal sodium levels both before and after their hyponatremic episode, and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m2. Exclusion criteria included heart failure, cirrhosis, and adrenal insufficiency.
Older white people with lower baseline sodium and eGFR values were most at risk. Contrary to previous reports, hyponatremia wasn’t more likely in men.
The mean sodium level during an episode was 130.2 mEq/L; the majority of patients eventually normalized and continued treatment.
Subjects in the main study were a mean of 66 years old, about two-thirds were white, and about 60% were women. The baseline eGFR was 77.2 mL/min/1.73 m2, and baseline sodium level 135.8 mEq/L.
All but one of the 14 substudy patients were women. Those who became hyponatremic when switched to spironolactone were older (mean 74.2 versus 65.8 years), had lower baseline eGFRs (63.7 versus 69.7 mL/min/1.73 m2), and were more likely to be white, but the differences were not statistically significant.
There was no external funding, and the investigators didn’t have any industry disclosures.
SOURCE: Matanes F et al. Joint Hypertension 2019, Abstracts 187 and 174.
NEW ORLEANS – .
The investigators reviewed hypertension patients whose treatment regimens included one diuretic. Forty on chlorthalidone developed hyponatremia – defined as a serum sodium below 133 mEq/L – across 1,322 prescriptions, for an incidence of 3.03%. There were 31 cases across 1,159 spironolactone prescriptions, an incidence of 2.67%.
Among 14 patients in a substudy who discontinued chlorthalidone after developing hyponatremia at a mean of about 2 weeks, six (43%) subsequently developed hyponatremia on spironolactone, also at an average of about 2 weeks.
The findings suggest that spironolactone is more likely than generally thought to cause hyponatremia, a potentially severe complication of diuretics, and that hyponatremia on chlorthalidone increases the risk, said lead investigator Faris Matanes, MD, a hypertension researcher at the university.
“We used to think” that hyponatremia on spironolactone was “very unlikely, but actually it’s not; the incidence is really close to chlorthalidone,” a well-known cause, and “if a patient develops hyponatremia on chlorthalidone, we should be more careful about giving them spironolactone,” he said.
Almost half the spironolactone cases were on 25 mg/day or less, and over a quarter of the chlorthalidone cases were on 12.5 mg/day. Of the 154 hyponatremia cases across 10,660 hydrochlorothiazide prescriptions (1.44%), over a third were taking 12.5 mg/day or less.
Overall, hyponatremia was diagnosed at a mean of 40.4 days, but sometimes after 2 or more months of treatment.
The findings “mean that even if we start patients on a low dose, we can’t stop checking after one or two normal sodium levels.” Measurements need to be ongoing, Dr. Matanes said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
He and his team wanted to get around the limitations of previous diuretic hyponatremia studies, including use of more than one diuretic, markedly poor kidney function, and other confounders. To that end, the study was limited to outpatients on a single diuretic who had normal sodium levels both before and after their hyponatremic episode, and estimated glomerular filtration rates (eGFR) of at least 30 mL/min/1.73 m2. Exclusion criteria included heart failure, cirrhosis, and adrenal insufficiency.
Older white people with lower baseline sodium and eGFR values were most at risk. Contrary to previous reports, hyponatremia wasn’t more likely in men.
The mean sodium level during an episode was 130.2 mEq/L; the majority of patients eventually normalized and continued treatment.
Subjects in the main study were a mean of 66 years old, about two-thirds were white, and about 60% were women. The baseline eGFR was 77.2 mL/min/1.73 m2, and baseline sodium level 135.8 mEq/L.
All but one of the 14 substudy patients were women. Those who became hyponatremic when switched to spironolactone were older (mean 74.2 versus 65.8 years), had lower baseline eGFRs (63.7 versus 69.7 mL/min/1.73 m2), and were more likely to be white, but the differences were not statistically significant.
There was no external funding, and the investigators didn’t have any industry disclosures.
SOURCE: Matanes F et al. Joint Hypertension 2019, Abstracts 187 and 174.
REPORTING FROM JOINT HYPERTENSION 2019
ABPM rarely used for hypertension management in United States
NEW ORLEANS – , according to a University of Florida, Gainesville, analysis of claims data for almost 4 million people.
“With each iteration, evidence-based guidelines have more strongly recommended out-of-office blood pressure measurement, but it’s basically had no impact. If we are going to continue to recommend this aggressively, we need to put some pressure on both payers and providers,” said lead investigator Steven M. Smith, PharmD, of the department of pharmacotherapy & translational research, associate director of the Center for Integrative Cardiovascular and Metabolic Diseases at the university.
“A number of studies show that ambulatory blood pressure monitoring [ABPM] is more strongly predictive of outcomes than office pressure.” It’s “considered the gold standard for hypertension,” he said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension
The reason is that ABPM gives a continual reading of blood pressure over 24 hours, not just an office snapshot, and can do things that office measurements cannot, including ruling out white coat hypertension, identifying masked hypertension, and checking nocturnal dipping and morning surge, both of which are related to cardiovascular risk.
Although common in Canada and Europe, it’s no secret that ABPM hasn’t caught on in the United States. The goal of Dr. Smith’s work was to help quantify the situation.
Using Truven Health Analytics commercial insurance claims data, he and his team identified 3,378,645 adults starting their first hypertension medication and 335,200 starting their fourth from 2008 to 2017. They looked for ABPM claims in the previous 6 months as well as the month after patients started their new medication. The idea was to assess ABPM use in both new and resistant hypertensive patients.
ABPM claims were submitted for 0.15% of patients starting their first drug in 2008, rising to 0.3% in 2017. ABPM was used mostly before treatment initiation.
ABPM use actually declined among resistant patients from about 0.27% in 2008 to about 0.12% in 2017. Use was split about evenly before and after they started their fourth medication.
About 80% of claims – generally for interpreting ABPM results, not the upfront cost of the machine – were paid. Claims submitted tended to come from more high-end plans. Reimbursement rates were similar for more bargain plans, but there were many fewer claims submitted, Dr. Smith said.
He thought plans would at least follow Medicare’s reimbursement policy, which, at the time of the study, covered ABPM to rule out white coat hypertension, “but they didn’t seem to,” he said. Medicare recently added coverage for suspected masked hypertension.
The study doesn’t address why uptake is so low in the United States, but outside the world of hypertension specialists, “physicians don’t see a value in it. They don’t recognize what they would get from ABPM and how that would change what they do,” in part because treatment is currently based on office measurements. There’s also probably uncertainty about how to interpret the results, Dr. Smith said.
Standardization across payers about what they’ll cover and for whom would probably help, he added.
Findings in the study were similar for home blood pressure monitoring, but probably not an accurate gauge of use. Patients mostly buy their own devices and report the results to their physician, without getting insurance involved, he said.
There was no industry funding, and the investigators didn’t have any disclosures.
SOURCE: Smith SM et al. Joint Hypertension 2019, Abstract P2067.
NEW ORLEANS – , according to a University of Florida, Gainesville, analysis of claims data for almost 4 million people.
“With each iteration, evidence-based guidelines have more strongly recommended out-of-office blood pressure measurement, but it’s basically had no impact. If we are going to continue to recommend this aggressively, we need to put some pressure on both payers and providers,” said lead investigator Steven M. Smith, PharmD, of the department of pharmacotherapy & translational research, associate director of the Center for Integrative Cardiovascular and Metabolic Diseases at the university.
“A number of studies show that ambulatory blood pressure monitoring [ABPM] is more strongly predictive of outcomes than office pressure.” It’s “considered the gold standard for hypertension,” he said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension
The reason is that ABPM gives a continual reading of blood pressure over 24 hours, not just an office snapshot, and can do things that office measurements cannot, including ruling out white coat hypertension, identifying masked hypertension, and checking nocturnal dipping and morning surge, both of which are related to cardiovascular risk.
Although common in Canada and Europe, it’s no secret that ABPM hasn’t caught on in the United States. The goal of Dr. Smith’s work was to help quantify the situation.
Using Truven Health Analytics commercial insurance claims data, he and his team identified 3,378,645 adults starting their first hypertension medication and 335,200 starting their fourth from 2008 to 2017. They looked for ABPM claims in the previous 6 months as well as the month after patients started their new medication. The idea was to assess ABPM use in both new and resistant hypertensive patients.
ABPM claims were submitted for 0.15% of patients starting their first drug in 2008, rising to 0.3% in 2017. ABPM was used mostly before treatment initiation.
ABPM use actually declined among resistant patients from about 0.27% in 2008 to about 0.12% in 2017. Use was split about evenly before and after they started their fourth medication.
About 80% of claims – generally for interpreting ABPM results, not the upfront cost of the machine – were paid. Claims submitted tended to come from more high-end plans. Reimbursement rates were similar for more bargain plans, but there were many fewer claims submitted, Dr. Smith said.
He thought plans would at least follow Medicare’s reimbursement policy, which, at the time of the study, covered ABPM to rule out white coat hypertension, “but they didn’t seem to,” he said. Medicare recently added coverage for suspected masked hypertension.
The study doesn’t address why uptake is so low in the United States, but outside the world of hypertension specialists, “physicians don’t see a value in it. They don’t recognize what they would get from ABPM and how that would change what they do,” in part because treatment is currently based on office measurements. There’s also probably uncertainty about how to interpret the results, Dr. Smith said.
Standardization across payers about what they’ll cover and for whom would probably help, he added.
Findings in the study were similar for home blood pressure monitoring, but probably not an accurate gauge of use. Patients mostly buy their own devices and report the results to their physician, without getting insurance involved, he said.
There was no industry funding, and the investigators didn’t have any disclosures.
SOURCE: Smith SM et al. Joint Hypertension 2019, Abstract P2067.
NEW ORLEANS – , according to a University of Florida, Gainesville, analysis of claims data for almost 4 million people.
“With each iteration, evidence-based guidelines have more strongly recommended out-of-office blood pressure measurement, but it’s basically had no impact. If we are going to continue to recommend this aggressively, we need to put some pressure on both payers and providers,” said lead investigator Steven M. Smith, PharmD, of the department of pharmacotherapy & translational research, associate director of the Center for Integrative Cardiovascular and Metabolic Diseases at the university.
“A number of studies show that ambulatory blood pressure monitoring [ABPM] is more strongly predictive of outcomes than office pressure.” It’s “considered the gold standard for hypertension,” he said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension
The reason is that ABPM gives a continual reading of blood pressure over 24 hours, not just an office snapshot, and can do things that office measurements cannot, including ruling out white coat hypertension, identifying masked hypertension, and checking nocturnal dipping and morning surge, both of which are related to cardiovascular risk.
Although common in Canada and Europe, it’s no secret that ABPM hasn’t caught on in the United States. The goal of Dr. Smith’s work was to help quantify the situation.
Using Truven Health Analytics commercial insurance claims data, he and his team identified 3,378,645 adults starting their first hypertension medication and 335,200 starting their fourth from 2008 to 2017. They looked for ABPM claims in the previous 6 months as well as the month after patients started their new medication. The idea was to assess ABPM use in both new and resistant hypertensive patients.
ABPM claims were submitted for 0.15% of patients starting their first drug in 2008, rising to 0.3% in 2017. ABPM was used mostly before treatment initiation.
ABPM use actually declined among resistant patients from about 0.27% in 2008 to about 0.12% in 2017. Use was split about evenly before and after they started their fourth medication.
About 80% of claims – generally for interpreting ABPM results, not the upfront cost of the machine – were paid. Claims submitted tended to come from more high-end plans. Reimbursement rates were similar for more bargain plans, but there were many fewer claims submitted, Dr. Smith said.
He thought plans would at least follow Medicare’s reimbursement policy, which, at the time of the study, covered ABPM to rule out white coat hypertension, “but they didn’t seem to,” he said. Medicare recently added coverage for suspected masked hypertension.
The study doesn’t address why uptake is so low in the United States, but outside the world of hypertension specialists, “physicians don’t see a value in it. They don’t recognize what they would get from ABPM and how that would change what they do,” in part because treatment is currently based on office measurements. There’s also probably uncertainty about how to interpret the results, Dr. Smith said.
Standardization across payers about what they’ll cover and for whom would probably help, he added.
Findings in the study were similar for home blood pressure monitoring, but probably not an accurate gauge of use. Patients mostly buy their own devices and report the results to their physician, without getting insurance involved, he said.
There was no industry funding, and the investigators didn’t have any disclosures.
SOURCE: Smith SM et al. Joint Hypertension 2019, Abstract P2067.
REPORTING FROM JOINT HYPERTENSION 2019
Daily polypill lowers BP, cholesterol in underserved population
A daily polypill regimen improved cardiovascular risk factors in a socioeconomically vulnerable minority population, in a randomized controlled trial.
Patients at a federally qualified community health center in Alabama who received treatment with a combination pill for 1 year had greater reductions in systolic blood pressure and LDL cholesterol than did patients who received usual care, according to results published online on Sept. 19 in the New England Journal of Medicine.
“The simplicity and low cost of the polypill regimen make this approach attractive” when barriers such as lack of income, underinsurance, and difficulty attending clinic visits are common, said first author Daniel Muñoz, MD, of Vanderbilt University in Nashville, and coinvestigators. The investigators obtained the pills at a cost of $26 per month per participant.
People with low socioeconomic status and those who are nonwhite have high cardiovascular mortality, and the southeastern United States and rural areas have disproportionately high levels of cardiovascular disease burden, according to the investigators. The rates at which people with low socioeconomic status receive treatment for hypertension and hypercholesterolemia – leading cardiovascular disease risk factors – “are strikingly low,” Dr. Muñoz and colleagues said.
To assess the effectiveness of a polypill-based strategy in an underserved population with low socioeconomic status, the researchers conducted the randomized trial.
They enrolled 303 adults without cardiovascular disease, and 148 of the patients were randomized to receive the polypill, which contained generic versions of atorvastatin (10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The remaining 155 patients received usual care. All participants scheduled 2-month and 12-month follow-up visits.
The participants had an average age of 56 years, 60% were women, and more than 95% were black. More than 70% had an annual household income of less than $15,000. Baseline characteristics of the treatment groups did not significantly differ.
At baseline, the average BP was 140/83 mm Hg, and the average LDL cholesterol level was 113 mg/dL.
In all, 91% of the participants completed the 12-month trial visit. Average systolic BP decreased by 9 mm Hg in the group that received the polypill, compared with 2 mm Hg in the group that received usual care. Average LDL cholesterol level decreased by 15 mg/dL in the polypill group, versus 4 mg/dL in the usual-care group.
Changes in other medications
Clinicians discontinued or reduced doses of other antihypertensive or lipid-lowering medications in 44% of the patients in the polypill group and none in the usual-care group. Clinicians escalated therapy in 2% of the participants in the polypill group and in 10% of the usual-care group.
Side effects in participants who received the polypill included a 1% incidence of myalgias and a 1% incidence of hypotension or light-headedness. Liver function test results were normal.
Five serious adverse events that occurred during the trial – two in the polypill group and three in the usual-care group – were judged to be unrelated to the trial by a data and safety monitoring board.
The authors noted that limitations of the trial include its open-label design and that it was conducted at a single center.
“It is important to emphasize that use of the polypill does not preclude individualized, add-on therapies for residual elevations in blood-pressure or cholesterol levels, as judged by a patient’s physician,” said Dr. Muñoz and colleagues. “We recognize that a ‘one size fits all’ approach to cardiovascular disease prevention runs counter to current trends in precision medicine, in which clinical, genomic, and lifestyle factors are used for the development of individualized treatment strategies. Although the precision approach has clear virtues, a broader approach may benefit patients who face barriers to accessing the full advantages of precision medicine.”
The study was supported by grants from the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health. One author disclosed personal fees from Novartis outside the study.
SOURCE: Muñoz D et al. N Engl J Med. 2019 Sep 18;381(12):1114-23. doi: 10.1056/NEJMoa1815359.
A daily polypill regimen improved cardiovascular risk factors in a socioeconomically vulnerable minority population, in a randomized controlled trial.
Patients at a federally qualified community health center in Alabama who received treatment with a combination pill for 1 year had greater reductions in systolic blood pressure and LDL cholesterol than did patients who received usual care, according to results published online on Sept. 19 in the New England Journal of Medicine.
“The simplicity and low cost of the polypill regimen make this approach attractive” when barriers such as lack of income, underinsurance, and difficulty attending clinic visits are common, said first author Daniel Muñoz, MD, of Vanderbilt University in Nashville, and coinvestigators. The investigators obtained the pills at a cost of $26 per month per participant.
People with low socioeconomic status and those who are nonwhite have high cardiovascular mortality, and the southeastern United States and rural areas have disproportionately high levels of cardiovascular disease burden, according to the investigators. The rates at which people with low socioeconomic status receive treatment for hypertension and hypercholesterolemia – leading cardiovascular disease risk factors – “are strikingly low,” Dr. Muñoz and colleagues said.
To assess the effectiveness of a polypill-based strategy in an underserved population with low socioeconomic status, the researchers conducted the randomized trial.
They enrolled 303 adults without cardiovascular disease, and 148 of the patients were randomized to receive the polypill, which contained generic versions of atorvastatin (10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The remaining 155 patients received usual care. All participants scheduled 2-month and 12-month follow-up visits.
The participants had an average age of 56 years, 60% were women, and more than 95% were black. More than 70% had an annual household income of less than $15,000. Baseline characteristics of the treatment groups did not significantly differ.
At baseline, the average BP was 140/83 mm Hg, and the average LDL cholesterol level was 113 mg/dL.
In all, 91% of the participants completed the 12-month trial visit. Average systolic BP decreased by 9 mm Hg in the group that received the polypill, compared with 2 mm Hg in the group that received usual care. Average LDL cholesterol level decreased by 15 mg/dL in the polypill group, versus 4 mg/dL in the usual-care group.
Changes in other medications
Clinicians discontinued or reduced doses of other antihypertensive or lipid-lowering medications in 44% of the patients in the polypill group and none in the usual-care group. Clinicians escalated therapy in 2% of the participants in the polypill group and in 10% of the usual-care group.
Side effects in participants who received the polypill included a 1% incidence of myalgias and a 1% incidence of hypotension or light-headedness. Liver function test results were normal.
Five serious adverse events that occurred during the trial – two in the polypill group and three in the usual-care group – were judged to be unrelated to the trial by a data and safety monitoring board.
The authors noted that limitations of the trial include its open-label design and that it was conducted at a single center.
“It is important to emphasize that use of the polypill does not preclude individualized, add-on therapies for residual elevations in blood-pressure or cholesterol levels, as judged by a patient’s physician,” said Dr. Muñoz and colleagues. “We recognize that a ‘one size fits all’ approach to cardiovascular disease prevention runs counter to current trends in precision medicine, in which clinical, genomic, and lifestyle factors are used for the development of individualized treatment strategies. Although the precision approach has clear virtues, a broader approach may benefit patients who face barriers to accessing the full advantages of precision medicine.”
The study was supported by grants from the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health. One author disclosed personal fees from Novartis outside the study.
SOURCE: Muñoz D et al. N Engl J Med. 2019 Sep 18;381(12):1114-23. doi: 10.1056/NEJMoa1815359.
A daily polypill regimen improved cardiovascular risk factors in a socioeconomically vulnerable minority population, in a randomized controlled trial.
Patients at a federally qualified community health center in Alabama who received treatment with a combination pill for 1 year had greater reductions in systolic blood pressure and LDL cholesterol than did patients who received usual care, according to results published online on Sept. 19 in the New England Journal of Medicine.
“The simplicity and low cost of the polypill regimen make this approach attractive” when barriers such as lack of income, underinsurance, and difficulty attending clinic visits are common, said first author Daniel Muñoz, MD, of Vanderbilt University in Nashville, and coinvestigators. The investigators obtained the pills at a cost of $26 per month per participant.
People with low socioeconomic status and those who are nonwhite have high cardiovascular mortality, and the southeastern United States and rural areas have disproportionately high levels of cardiovascular disease burden, according to the investigators. The rates at which people with low socioeconomic status receive treatment for hypertension and hypercholesterolemia – leading cardiovascular disease risk factors – “are strikingly low,” Dr. Muñoz and colleagues said.
To assess the effectiveness of a polypill-based strategy in an underserved population with low socioeconomic status, the researchers conducted the randomized trial.
They enrolled 303 adults without cardiovascular disease, and 148 of the patients were randomized to receive the polypill, which contained generic versions of atorvastatin (10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The remaining 155 patients received usual care. All participants scheduled 2-month and 12-month follow-up visits.
The participants had an average age of 56 years, 60% were women, and more than 95% were black. More than 70% had an annual household income of less than $15,000. Baseline characteristics of the treatment groups did not significantly differ.
At baseline, the average BP was 140/83 mm Hg, and the average LDL cholesterol level was 113 mg/dL.
In all, 91% of the participants completed the 12-month trial visit. Average systolic BP decreased by 9 mm Hg in the group that received the polypill, compared with 2 mm Hg in the group that received usual care. Average LDL cholesterol level decreased by 15 mg/dL in the polypill group, versus 4 mg/dL in the usual-care group.
Changes in other medications
Clinicians discontinued or reduced doses of other antihypertensive or lipid-lowering medications in 44% of the patients in the polypill group and none in the usual-care group. Clinicians escalated therapy in 2% of the participants in the polypill group and in 10% of the usual-care group.
Side effects in participants who received the polypill included a 1% incidence of myalgias and a 1% incidence of hypotension or light-headedness. Liver function test results were normal.
Five serious adverse events that occurred during the trial – two in the polypill group and three in the usual-care group – were judged to be unrelated to the trial by a data and safety monitoring board.
The authors noted that limitations of the trial include its open-label design and that it was conducted at a single center.
“It is important to emphasize that use of the polypill does not preclude individualized, add-on therapies for residual elevations in blood-pressure or cholesterol levels, as judged by a patient’s physician,” said Dr. Muñoz and colleagues. “We recognize that a ‘one size fits all’ approach to cardiovascular disease prevention runs counter to current trends in precision medicine, in which clinical, genomic, and lifestyle factors are used for the development of individualized treatment strategies. Although the precision approach has clear virtues, a broader approach may benefit patients who face barriers to accessing the full advantages of precision medicine.”
The study was supported by grants from the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health. One author disclosed personal fees from Novartis outside the study.
SOURCE: Muñoz D et al. N Engl J Med. 2019 Sep 18;381(12):1114-23. doi: 10.1056/NEJMoa1815359.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: A daily polypill regimen may improve cardiovascular disease prevention in underserved populations.
Major finding: Mean LDL cholesterol levels decreased by 15 mg/dL in the polypill group, vs. 4 mg/dL in the usual-care group.
Study details: An open-label, randomized trial that enrolled 303 adults without cardiovascular disease at a federally qualified community health center in Alabama.
Disclosures: The study was supported by grants from the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health. One author disclosed personal fees from Novartis outside the study.
Source: Muñoz D et al. N Engl J Med. 2019;381(12):1114-23. doi: 10.1056/NEJMoa1815359.
Remember that preeclampsia has a ‘fourth trimester’
NEW ORLEANS – according to Natalie Bello, MD, a cardiologist and assistant professor of medicine at Columbia University in New York.
In medical school, “they told me that you deliver the placenta, and the preeclampsia goes away. Not the case. Postpartum preeclampsia is a real thing. We are seeing a lot of it at our sites, which have a lot of underserved women who hadn’t had great prenatal care” elsewhere, she said.
Headache and visual changes in association with hypertension during what’s been dubbed “the fourth trimester” raise suspicions. Women can progress rapidly to eclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count), but sometimes providers don’t recognize what’s going on because they don’t know women have recently given birth. “We can do better; we should be doing better. Please always ask women if they’ve delivered recently,” Dr. Bello said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Hypertension should resolve within 6 weeks of delivery, and blood pressure should be back to baseline by 3 months. To make sure that happens, BP should be checked within a few days of birth and regularly thereafter. It can be tough to get busy and tired new moms back into the office, but “they’ll do whatever it takes” to get their baby to a pediatric appointment, so maybe having pediatricians involved in checking blood pressure would help, she said.
The cutoff point for hypertension in pregnancy is 140/90 mm Hg, and it’s considered severe when values hit 160/110 mm Hg or higher. Evidence is strong for treating severe hypertension to reduce strokes, placental abruptions, and other problems, but the data for treating nonsevere hypertension are less clear, Dr. Bello explained.
The Chronic Hypertension and Pregnancy (CHAP) trial is expected to fill the evidence gap in a few years; women are being randomized to start treatment at either 140/90 mm Hg or 160/105 mm Hg. Meanwhile, the American College of Obstetricians and Gynecologists recently suggested that treatment of nonsevere hypertension might be appropriate in the setting of comorbidities and renal dysfunction (Obstet Gynecol. 2019 Jan;133[1]:e26-e50).
Dr. Bello prefers treating with extended-release calcium channel blocker nifedipine over the beta-blocker labetalol. “We think it is a little more effective,” and the once daily dosing, instead of two or three times a day, helps with compliance. Thiazide diuretics and hydralazine are also in her arsenal, but hydralazine shouldn’t be used in isolation because of its reflex tachycardia risk. The old standby, the antiadrenergic methyldopa, has fallen out of favor because of depression and other concerns. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and mineralocorticoid receptor antagonists shouldn’t be used in pregnancy, she said.
Intravenous labetalol and short-acting oral nifedipine are the mainstays for urgent, severe hypertension, along with high-dose intravenous magnesium, especially for seizure control. IV hydralazine or nitroglycerin are other options, the latter particularly for pulmonary edema. “Be careful of synergistic hypotension with magnesium and nifedipine,” Dr. Bello said.
Dr. Bello didn’t have any industry disclosures.
NEW ORLEANS – according to Natalie Bello, MD, a cardiologist and assistant professor of medicine at Columbia University in New York.
In medical school, “they told me that you deliver the placenta, and the preeclampsia goes away. Not the case. Postpartum preeclampsia is a real thing. We are seeing a lot of it at our sites, which have a lot of underserved women who hadn’t had great prenatal care” elsewhere, she said.
Headache and visual changes in association with hypertension during what’s been dubbed “the fourth trimester” raise suspicions. Women can progress rapidly to eclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count), but sometimes providers don’t recognize what’s going on because they don’t know women have recently given birth. “We can do better; we should be doing better. Please always ask women if they’ve delivered recently,” Dr. Bello said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Hypertension should resolve within 6 weeks of delivery, and blood pressure should be back to baseline by 3 months. To make sure that happens, BP should be checked within a few days of birth and regularly thereafter. It can be tough to get busy and tired new moms back into the office, but “they’ll do whatever it takes” to get their baby to a pediatric appointment, so maybe having pediatricians involved in checking blood pressure would help, she said.
The cutoff point for hypertension in pregnancy is 140/90 mm Hg, and it’s considered severe when values hit 160/110 mm Hg or higher. Evidence is strong for treating severe hypertension to reduce strokes, placental abruptions, and other problems, but the data for treating nonsevere hypertension are less clear, Dr. Bello explained.
The Chronic Hypertension and Pregnancy (CHAP) trial is expected to fill the evidence gap in a few years; women are being randomized to start treatment at either 140/90 mm Hg or 160/105 mm Hg. Meanwhile, the American College of Obstetricians and Gynecologists recently suggested that treatment of nonsevere hypertension might be appropriate in the setting of comorbidities and renal dysfunction (Obstet Gynecol. 2019 Jan;133[1]:e26-e50).
Dr. Bello prefers treating with extended-release calcium channel blocker nifedipine over the beta-blocker labetalol. “We think it is a little more effective,” and the once daily dosing, instead of two or three times a day, helps with compliance. Thiazide diuretics and hydralazine are also in her arsenal, but hydralazine shouldn’t be used in isolation because of its reflex tachycardia risk. The old standby, the antiadrenergic methyldopa, has fallen out of favor because of depression and other concerns. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and mineralocorticoid receptor antagonists shouldn’t be used in pregnancy, she said.
Intravenous labetalol and short-acting oral nifedipine are the mainstays for urgent, severe hypertension, along with high-dose intravenous magnesium, especially for seizure control. IV hydralazine or nitroglycerin are other options, the latter particularly for pulmonary edema. “Be careful of synergistic hypotension with magnesium and nifedipine,” Dr. Bello said.
Dr. Bello didn’t have any industry disclosures.
NEW ORLEANS – according to Natalie Bello, MD, a cardiologist and assistant professor of medicine at Columbia University in New York.
In medical school, “they told me that you deliver the placenta, and the preeclampsia goes away. Not the case. Postpartum preeclampsia is a real thing. We are seeing a lot of it at our sites, which have a lot of underserved women who hadn’t had great prenatal care” elsewhere, she said.
Headache and visual changes in association with hypertension during what’s been dubbed “the fourth trimester” raise suspicions. Women can progress rapidly to eclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count), but sometimes providers don’t recognize what’s going on because they don’t know women have recently given birth. “We can do better; we should be doing better. Please always ask women if they’ve delivered recently,” Dr. Bello said at the joint scientific sessions of the American Heart Association Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.
Hypertension should resolve within 6 weeks of delivery, and blood pressure should be back to baseline by 3 months. To make sure that happens, BP should be checked within a few days of birth and regularly thereafter. It can be tough to get busy and tired new moms back into the office, but “they’ll do whatever it takes” to get their baby to a pediatric appointment, so maybe having pediatricians involved in checking blood pressure would help, she said.
The cutoff point for hypertension in pregnancy is 140/90 mm Hg, and it’s considered severe when values hit 160/110 mm Hg or higher. Evidence is strong for treating severe hypertension to reduce strokes, placental abruptions, and other problems, but the data for treating nonsevere hypertension are less clear, Dr. Bello explained.
The Chronic Hypertension and Pregnancy (CHAP) trial is expected to fill the evidence gap in a few years; women are being randomized to start treatment at either 140/90 mm Hg or 160/105 mm Hg. Meanwhile, the American College of Obstetricians and Gynecologists recently suggested that treatment of nonsevere hypertension might be appropriate in the setting of comorbidities and renal dysfunction (Obstet Gynecol. 2019 Jan;133[1]:e26-e50).
Dr. Bello prefers treating with extended-release calcium channel blocker nifedipine over the beta-blocker labetalol. “We think it is a little more effective,” and the once daily dosing, instead of two or three times a day, helps with compliance. Thiazide diuretics and hydralazine are also in her arsenal, but hydralazine shouldn’t be used in isolation because of its reflex tachycardia risk. The old standby, the antiadrenergic methyldopa, has fallen out of favor because of depression and other concerns. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and mineralocorticoid receptor antagonists shouldn’t be used in pregnancy, she said.
Intravenous labetalol and short-acting oral nifedipine are the mainstays for urgent, severe hypertension, along with high-dose intravenous magnesium, especially for seizure control. IV hydralazine or nitroglycerin are other options, the latter particularly for pulmonary edema. “Be careful of synergistic hypotension with magnesium and nifedipine,” Dr. Bello said.
Dr. Bello didn’t have any industry disclosures.
EXPERT ANALYSIS FROM JOINT HYPERTENSION 2019
