Lipid Disorders

SAN FRANCISCO – Powerful drugs now make it possible to lower LDL cholesterol levels to dramatically low levels. But is this a good idea? There are risks, and a cardiologist urged diabetes professionals to not overdo cholesterol reduction. But a colleague argued in favor of aggressively targeting “bad” cholesterol.

Catherine Hackett

“We used to say you can’t be too rich or too thin. We now say you can’t be too rich or too thin or have a too-low LDL cholesterol,” said cardiologist Steven E. Nissen, MD, chairman of cardiovascular medicine at the Cleveland Clinic Foundation, who spoke at the annual scientific sessions of the American Diabetes Association about the wisdom of extreme LDL cholesterol lowering.

Dr. Nissen faced off in a debate with cardiologist Sanket Dhruva, MD, of the University of California, San Francisco, who doesn’t support aggressive LDL cholesterol lowering.

It is fine, Dr. Dhruva said, to treat patients so their LDL cholesterol levels drop below 100 mg/dL. “I don’t think there’s any argument there.”

But Dr. Dhruva questioned whether it’s a good idea to generally decrease LDL cholesterol well below 70 mg/dL, as is now possible with the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

SAN FRANCISCO – Powerful drugs now make it possible to lower LDL cholesterol levels to dramatically low levels. But is this a good idea? There are risks, and a cardiologist urged diabetes professionals to not overdo cholesterol reduction. But a colleague argued in favor of aggressively targeting “bad” cholesterol.

Catherine Hackett

“We used to say you can’t be too rich or too thin. We now say you can’t be too rich or too thin or have a too-low LDL cholesterol,” said cardiologist Steven E. Nissen, MD, chairman of cardiovascular medicine at the Cleveland Clinic Foundation, who spoke at the annual scientific sessions of the American Diabetes Association about the wisdom of extreme LDL cholesterol lowering.

Dr. Nissen faced off in a debate with cardiologist Sanket Dhruva, MD, of the University of California, San Francisco, who doesn’t support aggressive LDL cholesterol lowering.

It is fine, Dr. Dhruva said, to treat patients so their LDL cholesterol levels drop below 100 mg/dL. “I don’t think there’s any argument there.”

But Dr. Dhruva questioned whether it’s a good idea to generally decrease LDL cholesterol well below 70 mg/dL, as is now possible with the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

SAN FRANCISCO – Powerful drugs now make it possible to lower LDL cholesterol levels to dramatically low levels. But is this a good idea? There are risks, and a cardiologist urged diabetes professionals to not overdo cholesterol reduction. But a colleague argued in favor of aggressively targeting “bad” cholesterol.

Catherine Hackett

“We used to say you can’t be too rich or too thin. We now say you can’t be too rich or too thin or have a too-low LDL cholesterol,” said cardiologist Steven E. Nissen, MD, chairman of cardiovascular medicine at the Cleveland Clinic Foundation, who spoke at the annual scientific sessions of the American Diabetes Association about the wisdom of extreme LDL cholesterol lowering.

Dr. Nissen faced off in a debate with cardiologist Sanket Dhruva, MD, of the University of California, San Francisco, who doesn’t support aggressive LDL cholesterol lowering.

It is fine, Dr. Dhruva said, to treat patients so their LDL cholesterol levels drop below 100 mg/dL. “I don’t think there’s any argument there.”

But Dr. Dhruva questioned whether it’s a good idea to generally decrease LDL cholesterol well below 70 mg/dL, as is now possible with the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Long-term genetically low levels of LDL cholesterol, by means of functional variants in the PCSK9 gene, were associated with a reduced risk of CV mortality, but not all-cause mortality, in a large cohort of individuals.

ktsimage/Thinkstock

“We tested the hypothesis that genetically low LDL cholesterol due to PCSK9 [proprotein convertase subtilisin/kexin type 9] variation is causally associated with low cardiovascular and all-cause mortality in a general population of Northern European ancestry,” wrote Marianne Benn, MD, DMSc, and colleagues. The findings were published in the Journal of the American College of Cardiology.

The researchers conducted a large-scale genetic analysis of 109,566 persons from the Copenhagen City Heart Study and Copenhagen General Population Study. In addition, the team included a validation cohort of 431,043 individuals from the UK Biobank.

The median duration of follow-up was 10 years (0-42 years), and the median age at study entry was 57 years.

Study participants were genotyped for several PCSK9 variants and a weighted allele score based the effects of LDL cholesterol, individual allele frequency, and number of variant alleles was calculated for each subject.

Weighted scores were categorized into five stepwise noncontinuous score ranges, with lower levels of LDL cholesterol linked to higher allele scores.

After analysis, the researchers found that a growing number of PCSK9 alleles were associated with lower levels of LDL cholesterol up to 0.61 mmol/L (P for trend less than .001) and reduced CV mortality (P = .001), but not with reduced all-cause mortality (P = .11).

“Our genetic data did not show a reduction in risk of all-cause mortality, and only showed a reduction in risk of all-cause mortality in statin trials and not in the PCSK9-inhibitor trials meta-analyzed,” the researchers wrote. “This may be explained by the low frequency of cardiovascular disease in the 2 populations studied,” they explained.

One key limitation was the homogeneous makeup of the study population. Dr. Benn and colleagues acknowledged this could limit the generalizability of the results.

“Long-term LDL cholesterol treatment (e.g., with PCSK9 inhibitors), may translate into reductions in cardiovascular mortality,” they concluded.

The study was supported by the Danish Council for Independent Research, Medical Sciences, Johan Boserup, and the Lise Boserup’s Fund. The authors reported no conflicts of interest.

SOURCE: Benn M et al. JACC. 2019 Jun 17. doi: 10.1016/j.jacc.2019.03.517

Long-term genetically low levels of LDL cholesterol, by means of functional variants in the PCSK9 gene, were associated with a reduced risk of CV mortality, but not all-cause mortality, in a large cohort of individuals.

ktsimage/Thinkstock

“We tested the hypothesis that genetically low LDL cholesterol due to PCSK9 [proprotein convertase subtilisin/kexin type 9] variation is causally associated with low cardiovascular and all-cause mortality in a general population of Northern European ancestry,” wrote Marianne Benn, MD, DMSc, and colleagues. The findings were published in the Journal of the American College of Cardiology.

The researchers conducted a large-scale genetic analysis of 109,566 persons from the Copenhagen City Heart Study and Copenhagen General Population Study. In addition, the team included a validation cohort of 431,043 individuals from the UK Biobank.

The median duration of follow-up was 10 years (0-42 years), and the median age at study entry was 57 years.

Study participants were genotyped for several PCSK9 variants and a weighted allele score based the effects of LDL cholesterol, individual allele frequency, and number of variant alleles was calculated for each subject.

Weighted scores were categorized into five stepwise noncontinuous score ranges, with lower levels of LDL cholesterol linked to higher allele scores.

After analysis, the researchers found that a growing number of PCSK9 alleles were associated with lower levels of LDL cholesterol up to 0.61 mmol/L (P for trend less than .001) and reduced CV mortality (P = .001), but not with reduced all-cause mortality (P = .11).

“Our genetic data did not show a reduction in risk of all-cause mortality, and only showed a reduction in risk of all-cause mortality in statin trials and not in the PCSK9-inhibitor trials meta-analyzed,” the researchers wrote. “This may be explained by the low frequency of cardiovascular disease in the 2 populations studied,” they explained.

One key limitation was the homogeneous makeup of the study population. Dr. Benn and colleagues acknowledged this could limit the generalizability of the results.

“Long-term LDL cholesterol treatment (e.g., with PCSK9 inhibitors), may translate into reductions in cardiovascular mortality,” they concluded.

The study was supported by the Danish Council for Independent Research, Medical Sciences, Johan Boserup, and the Lise Boserup’s Fund. The authors reported no conflicts of interest.

SOURCE: Benn M et al. JACC. 2019 Jun 17. doi: 10.1016/j.jacc.2019.03.517

Long-term genetically low levels of LDL cholesterol, by means of functional variants in the PCSK9 gene, were associated with a reduced risk of CV mortality, but not all-cause mortality, in a large cohort of individuals.

ktsimage/Thinkstock

“We tested the hypothesis that genetically low LDL cholesterol due to PCSK9 [proprotein convertase subtilisin/kexin type 9] variation is causally associated with low cardiovascular and all-cause mortality in a general population of Northern European ancestry,” wrote Marianne Benn, MD, DMSc, and colleagues. The findings were published in the Journal of the American College of Cardiology.

The researchers conducted a large-scale genetic analysis of 109,566 persons from the Copenhagen City Heart Study and Copenhagen General Population Study. In addition, the team included a validation cohort of 431,043 individuals from the UK Biobank.

The median duration of follow-up was 10 years (0-42 years), and the median age at study entry was 57 years.

Study participants were genotyped for several PCSK9 variants and a weighted allele score based the effects of LDL cholesterol, individual allele frequency, and number of variant alleles was calculated for each subject.

Weighted scores were categorized into five stepwise noncontinuous score ranges, with lower levels of LDL cholesterol linked to higher allele scores.

After analysis, the researchers found that a growing number of PCSK9 alleles were associated with lower levels of LDL cholesterol up to 0.61 mmol/L (P for trend less than .001) and reduced CV mortality (P = .001), but not with reduced all-cause mortality (P = .11).

“Our genetic data did not show a reduction in risk of all-cause mortality, and only showed a reduction in risk of all-cause mortality in statin trials and not in the PCSK9-inhibitor trials meta-analyzed,” the researchers wrote. “This may be explained by the low frequency of cardiovascular disease in the 2 populations studied,” they explained.

One key limitation was the homogeneous makeup of the study population. Dr. Benn and colleagues acknowledged this could limit the generalizability of the results.

“Long-term LDL cholesterol treatment (e.g., with PCSK9 inhibitors), may translate into reductions in cardiovascular mortality,” they concluded.

The study was supported by the Danish Council for Independent Research, Medical Sciences, Johan Boserup, and the Lise Boserup’s Fund. The authors reported no conflicts of interest.

SOURCE: Benn M et al. JACC. 2019 Jun 17. doi: 10.1016/j.jacc.2019.03.517

SAN FRANCISCO – New research suggests that the health of Americans with diabetes changed markedly in the past 2 decades, improving on three out of five fronts.

©Tashatuvango/Thinkstockphotos.com

As the age of statins dawned, cholesterol levels dipped dramatically, while blood pressure levels and smoking prevalence also fell. But hemoglobin A_1c levels stubbornly stayed steady, and obesity rates ballooned.

In light of the not entirely impressive numbers, “maybe we need to follow the model of team collaboration we see in the heart care setting,” said study lead author Carla I. Mercado, PhD, an epidemiologist with the Centers for Disease Control & Prevention. She spoke in an interview at the annual scientific sessions of the American Diabetes Association, where she presented the study findings.

For the new study, Dr. Mercado and colleagues used data from the National Health and Nutrition Examination Survey (NHANES) to track the health of adults with diabetes in the United States during 1999-2016. “With all the efforts on diabetes care management, we wanted to see if our efforts are making a difference in the population,” Dr. Mercado said.

The 5,534 participants had self-reported diabetes, were not pregnant, and underwent a physical examination. Throughout the periods examined (1999-2004, 2005-2010, and 2011-2016), the proportion of women remained steady at about one-half. So did the racial makeup, which ranged from 59% to 63% non-Hispanic white, 15% to 18% black, 7% to 10% Mexican-American, and 12% to 15% “other.”

Nearly half were aged 45-64, and 89%-90% had health insurance. There was a significant change in the education levels among those aged 25 and older: The percentage with at least a college degree grew from 14% in 1999-2004 to 21% in 2011-2016, while those with less than a high-school diploma fell from 34% to 23% over that period.

From 1999-2004 to 2011-2016

• Cholesterol: Most notably, the percentage of participants with non-HDL cholesterol levels below 130 mg/dL soared, from 30% to 54%. The CDC considers levels less than 100 mg/dL to be ideal. “I’m sure this is driven by medication use,” Dr. Mercado said.
• Smoking: The percentage of never smokers rose, from 44% to 47% of the subjects, while that of current smokers dropped, from 26% to 21%, a significant difference.
• Hypertension: The percentages with blood pressure levels less than 120/80 mm Hg – considered normal levels by the CDC – rose significantly, from 26% to 30%. “People are a lot more aware of blood pressure,” Dr. Mercado said.
• Glycemic control: HbA_1c levels stayed roughly steady. About 10% had levels at or above 10% in both 1999-2004 and 2011-2016, and the number with A_1c levels below 6% dipped slightly from 19% to 17%.
• Obesity: The proportion of participants with body mass index levels at or above 30 kg/m², the line between overweight and obese, rose from 54% to 61%. The percentage of those with BMIs below 25 kg/m² – considered to have normal weights – fell significantly, from 17% to 12%.

The researchers also looked at the percentage who reached ABCS goals (A_1c at or below 9%, blood pressure below 140/90 mm Hg, non-HDL cholesterol under 160 mg/dL, and current nonsmoking status). The percentage who met all of these criteria grew from 26% to 40%, while those who met three of them stayed steady (40%-39%).

The study was funded by the CDC. The study authors report no relevant disclosures.

SAN FRANCISCO – New research suggests that the health of Americans with diabetes changed markedly in the past 2 decades, improving on three out of five fronts.

©Tashatuvango/Thinkstockphotos.com

As the age of statins dawned, cholesterol levels dipped dramatically, while blood pressure levels and smoking prevalence also fell. But hemoglobin A_1c levels stubbornly stayed steady, and obesity rates ballooned.

In light of the not entirely impressive numbers, “maybe we need to follow the model of team collaboration we see in the heart care setting,” said study lead author Carla I. Mercado, PhD, an epidemiologist with the Centers for Disease Control & Prevention. She spoke in an interview at the annual scientific sessions of the American Diabetes Association, where she presented the study findings.

For the new study, Dr. Mercado and colleagues used data from the National Health and Nutrition Examination Survey (NHANES) to track the health of adults with diabetes in the United States during 1999-2016. “With all the efforts on diabetes care management, we wanted to see if our efforts are making a difference in the population,” Dr. Mercado said.

The 5,534 participants had self-reported diabetes, were not pregnant, and underwent a physical examination. Throughout the periods examined (1999-2004, 2005-2010, and 2011-2016), the proportion of women remained steady at about one-half. So did the racial makeup, which ranged from 59% to 63% non-Hispanic white, 15% to 18% black, 7% to 10% Mexican-American, and 12% to 15% “other.”

Nearly half were aged 45-64, and 89%-90% had health insurance. There was a significant change in the education levels among those aged 25 and older: The percentage with at least a college degree grew from 14% in 1999-2004 to 21% in 2011-2016, while those with less than a high-school diploma fell from 34% to 23% over that period.

From 1999-2004 to 2011-2016

• Cholesterol: Most notably, the percentage of participants with non-HDL cholesterol levels below 130 mg/dL soared, from 30% to 54%. The CDC considers levels less than 100 mg/dL to be ideal. “I’m sure this is driven by medication use,” Dr. Mercado said.
• Smoking: The percentage of never smokers rose, from 44% to 47% of the subjects, while that of current smokers dropped, from 26% to 21%, a significant difference.
• Hypertension: The percentages with blood pressure levels less than 120/80 mm Hg – considered normal levels by the CDC – rose significantly, from 26% to 30%. “People are a lot more aware of blood pressure,” Dr. Mercado said.
• Glycemic control: HbA_1c levels stayed roughly steady. About 10% had levels at or above 10% in both 1999-2004 and 2011-2016, and the number with A_1c levels below 6% dipped slightly from 19% to 17%.
• Obesity: The proportion of participants with body mass index levels at or above 30 kg/m², the line between overweight and obese, rose from 54% to 61%. The percentage of those with BMIs below 25 kg/m² – considered to have normal weights – fell significantly, from 17% to 12%.

The researchers also looked at the percentage who reached ABCS goals (A_1c at or below 9%, blood pressure below 140/90 mm Hg, non-HDL cholesterol under 160 mg/dL, and current nonsmoking status). The percentage who met all of these criteria grew from 26% to 40%, while those who met three of them stayed steady (40%-39%).

The study was funded by the CDC. The study authors report no relevant disclosures.

SAN FRANCISCO – New research suggests that the health of Americans with diabetes changed markedly in the past 2 decades, improving on three out of five fronts.

©Tashatuvango/Thinkstockphotos.com

As the age of statins dawned, cholesterol levels dipped dramatically, while blood pressure levels and smoking prevalence also fell. But hemoglobin A_1c levels stubbornly stayed steady, and obesity rates ballooned.

In light of the not entirely impressive numbers, “maybe we need to follow the model of team collaboration we see in the heart care setting,” said study lead author Carla I. Mercado, PhD, an epidemiologist with the Centers for Disease Control & Prevention. She spoke in an interview at the annual scientific sessions of the American Diabetes Association, where she presented the study findings.

For the new study, Dr. Mercado and colleagues used data from the National Health and Nutrition Examination Survey (NHANES) to track the health of adults with diabetes in the United States during 1999-2016. “With all the efforts on diabetes care management, we wanted to see if our efforts are making a difference in the population,” Dr. Mercado said.

The 5,534 participants had self-reported diabetes, were not pregnant, and underwent a physical examination. Throughout the periods examined (1999-2004, 2005-2010, and 2011-2016), the proportion of women remained steady at about one-half. So did the racial makeup, which ranged from 59% to 63% non-Hispanic white, 15% to 18% black, 7% to 10% Mexican-American, and 12% to 15% “other.”

Nearly half were aged 45-64, and 89%-90% had health insurance. There was a significant change in the education levels among those aged 25 and older: The percentage with at least a college degree grew from 14% in 1999-2004 to 21% in 2011-2016, while those with less than a high-school diploma fell from 34% to 23% over that period.

From 1999-2004 to 2011-2016

• Cholesterol: Most notably, the percentage of participants with non-HDL cholesterol levels below 130 mg/dL soared, from 30% to 54%. The CDC considers levels less than 100 mg/dL to be ideal. “I’m sure this is driven by medication use,” Dr. Mercado said.
• Smoking: The percentage of never smokers rose, from 44% to 47% of the subjects, while that of current smokers dropped, from 26% to 21%, a significant difference.
• Hypertension: The percentages with blood pressure levels less than 120/80 mm Hg – considered normal levels by the CDC – rose significantly, from 26% to 30%. “People are a lot more aware of blood pressure,” Dr. Mercado said.
• Glycemic control: HbA_1c levels stayed roughly steady. About 10% had levels at or above 10% in both 1999-2004 and 2011-2016, and the number with A_1c levels below 6% dipped slightly from 19% to 17%.
• Obesity: The proportion of participants with body mass index levels at or above 30 kg/m², the line between overweight and obese, rose from 54% to 61%. The percentage of those with BMIs below 25 kg/m² – considered to have normal weights – fell significantly, from 17% to 12%.

The researchers also looked at the percentage who reached ABCS goals (A_1c at or below 9%, blood pressure below 140/90 mm Hg, non-HDL cholesterol under 160 mg/dL, and current nonsmoking status). The percentage who met all of these criteria grew from 26% to 40%, while those who met three of them stayed steady (40%-39%).

The study was funded by the CDC. The study authors report no relevant disclosures.

SAN FRANCISCO – SGLT2 inhibitors did a better job than GLP-1 receptor agonists at preventing heart failure hospitalizations in elderly patients with type 2 diabetes, but at the cost of more strokes, myocardial infarctions, and deaths among those without preexisting cardiovascular disease, according to Harvard University investigators.

Using Medicare claims data and propensity scoring, they matched 43,609 elderly patients who started a sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes, 77% of whom were taking canagliflozin (Invokana), to 43,609 who started a glucagonlike peptide–1 (GLP-1)–receptor agonist, 60% of whom were taking liraglutide (Victoza).

Patients were paired by age, comorbidities, diabetes severity, and dozens of other variables, more than 120 in all. The data window ran from April 2013 through December 2016.

The idea was to compare the drugs directly in order to help clinicians decide which class to choose for older patients as second-line therapy, an important consideration at a time when there’s not much guidance specifically for the elderly, and manufacturers are issuing dueling placebo-controlled trials.

Both classes have shown cardiovascular benefits, but studies were mostly in younger people with preexisting cardiovascular disease (CVD). “The comparative impact of these agents in the older population has not yet been established,” lead investigator Elisabetta Patorno, MD, DrPH, of Harvard University, Boston, said at the annual scientific sessions of the American Diabetes Association.

General themes are emerging from Dr. Patorno’s work; it seems that deciding between the two classes has a lot to do with whether the main concern is heart failure or cardiovascular events. Even so, she said, it’s too early to incorporate the observations into guidelines. The analysis is ongoing, and there are plans to compare impacts on renal disease and other problems.

In the meantime, she and her colleagues found that initiating an SGLT2 inhibitor versus a GLP-1 receptor agonist in the elderly was associated with a 34% decreased risk of heart failure hospitalization (2.5 fewer hospitalizations per 1,000 patient years), with an even larger drop among people who had preexisting CVD.

There was, however, a 41% increased risk of lower limb amputations (0.8 more events per 1,000 patient years) and a 62% increase in diabetic ketoacidosis (DKA, 1 more event), problems previously associated with the class.

Results were comparable – fewer heart failure hospitalizations but more amputations and DKA – when SGLT2 initiation was compared to initiation with dipeptidyl peptidase-4 (DPP-4) inhibitors, another second-line option for type 2 diabetes that includes sitagliptin (Januvia), among others.

There was a 25% increased relative risk of the composite primary outcome of myocardial infarction, stroke, and all-cause mortality when patients without baseline CVD were started on an SGLT2 inhibitor instead of a GLP-1 receptor agonist (3.7 more events per 1,000 patient years). There was no increased risk among patients who already had CVD.

SGLT2 initiation actually had a protective effect, compared with dipeptidyl peptidase-4 inhibitors, with a 23% decreased risk of the composite outcome (6.5 fewer events) among patients both with and without baseline CVD. The findings were all statistically significant.

The average age in the study was 71.5 years; 45% of the subjects were men; 40% had a history of cardiovascular disease; and 60% were on metformin and 24% on insulin at study entry.

The work was funded by the National Institutes of Health. Dr. Patorno disclosed research grants form Boehringer Ingelheim and GlaxoSmithKline. Other investigators reported relationships with numerous pharmaceutical companies.

[email protected]

SAN FRANCISCO – SGLT2 inhibitors did a better job than GLP-1 receptor agonists at preventing heart failure hospitalizations in elderly patients with type 2 diabetes, but at the cost of more strokes, myocardial infarctions, and deaths among those without preexisting cardiovascular disease, according to Harvard University investigators.

Using Medicare claims data and propensity scoring, they matched 43,609 elderly patients who started a sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes, 77% of whom were taking canagliflozin (Invokana), to 43,609 who started a glucagonlike peptide–1 (GLP-1)–receptor agonist, 60% of whom were taking liraglutide (Victoza).

Patients were paired by age, comorbidities, diabetes severity, and dozens of other variables, more than 120 in all. The data window ran from April 2013 through December 2016.

The idea was to compare the drugs directly in order to help clinicians decide which class to choose for older patients as second-line therapy, an important consideration at a time when there’s not much guidance specifically for the elderly, and manufacturers are issuing dueling placebo-controlled trials.

Both classes have shown cardiovascular benefits, but studies were mostly in younger people with preexisting cardiovascular disease (CVD). “The comparative impact of these agents in the older population has not yet been established,” lead investigator Elisabetta Patorno, MD, DrPH, of Harvard University, Boston, said at the annual scientific sessions of the American Diabetes Association.

General themes are emerging from Dr. Patorno’s work; it seems that deciding between the two classes has a lot to do with whether the main concern is heart failure or cardiovascular events. Even so, she said, it’s too early to incorporate the observations into guidelines. The analysis is ongoing, and there are plans to compare impacts on renal disease and other problems.

In the meantime, she and her colleagues found that initiating an SGLT2 inhibitor versus a GLP-1 receptor agonist in the elderly was associated with a 34% decreased risk of heart failure hospitalization (2.5 fewer hospitalizations per 1,000 patient years), with an even larger drop among people who had preexisting CVD.

There was, however, a 41% increased risk of lower limb amputations (0.8 more events per 1,000 patient years) and a 62% increase in diabetic ketoacidosis (DKA, 1 more event), problems previously associated with the class.

Results were comparable – fewer heart failure hospitalizations but more amputations and DKA – when SGLT2 initiation was compared to initiation with dipeptidyl peptidase-4 (DPP-4) inhibitors, another second-line option for type 2 diabetes that includes sitagliptin (Januvia), among others.

There was a 25% increased relative risk of the composite primary outcome of myocardial infarction, stroke, and all-cause mortality when patients without baseline CVD were started on an SGLT2 inhibitor instead of a GLP-1 receptor agonist (3.7 more events per 1,000 patient years). There was no increased risk among patients who already had CVD.

SGLT2 initiation actually had a protective effect, compared with dipeptidyl peptidase-4 inhibitors, with a 23% decreased risk of the composite outcome (6.5 fewer events) among patients both with and without baseline CVD. The findings were all statistically significant.

The average age in the study was 71.5 years; 45% of the subjects were men; 40% had a history of cardiovascular disease; and 60% were on metformin and 24% on insulin at study entry.

The work was funded by the National Institutes of Health. Dr. Patorno disclosed research grants form Boehringer Ingelheim and GlaxoSmithKline. Other investigators reported relationships with numerous pharmaceutical companies.

[email protected]

SAN FRANCISCO – SGLT2 inhibitors did a better job than GLP-1 receptor agonists at preventing heart failure hospitalizations in elderly patients with type 2 diabetes, but at the cost of more strokes, myocardial infarctions, and deaths among those without preexisting cardiovascular disease, according to Harvard University investigators.

Using Medicare claims data and propensity scoring, they matched 43,609 elderly patients who started a sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes, 77% of whom were taking canagliflozin (Invokana), to 43,609 who started a glucagonlike peptide–1 (GLP-1)–receptor agonist, 60% of whom were taking liraglutide (Victoza).

Patients were paired by age, comorbidities, diabetes severity, and dozens of other variables, more than 120 in all. The data window ran from April 2013 through December 2016.

The idea was to compare the drugs directly in order to help clinicians decide which class to choose for older patients as second-line therapy, an important consideration at a time when there’s not much guidance specifically for the elderly, and manufacturers are issuing dueling placebo-controlled trials.

Both classes have shown cardiovascular benefits, but studies were mostly in younger people with preexisting cardiovascular disease (CVD). “The comparative impact of these agents in the older population has not yet been established,” lead investigator Elisabetta Patorno, MD, DrPH, of Harvard University, Boston, said at the annual scientific sessions of the American Diabetes Association.

General themes are emerging from Dr. Patorno’s work; it seems that deciding between the two classes has a lot to do with whether the main concern is heart failure or cardiovascular events. Even so, she said, it’s too early to incorporate the observations into guidelines. The analysis is ongoing, and there are plans to compare impacts on renal disease and other problems.

In the meantime, she and her colleagues found that initiating an SGLT2 inhibitor versus a GLP-1 receptor agonist in the elderly was associated with a 34% decreased risk of heart failure hospitalization (2.5 fewer hospitalizations per 1,000 patient years), with an even larger drop among people who had preexisting CVD.

There was, however, a 41% increased risk of lower limb amputations (0.8 more events per 1,000 patient years) and a 62% increase in diabetic ketoacidosis (DKA, 1 more event), problems previously associated with the class.

Results were comparable – fewer heart failure hospitalizations but more amputations and DKA – when SGLT2 initiation was compared to initiation with dipeptidyl peptidase-4 (DPP-4) inhibitors, another second-line option for type 2 diabetes that includes sitagliptin (Januvia), among others.

There was a 25% increased relative risk of the composite primary outcome of myocardial infarction, stroke, and all-cause mortality when patients without baseline CVD were started on an SGLT2 inhibitor instead of a GLP-1 receptor agonist (3.7 more events per 1,000 patient years). There was no increased risk among patients who already had CVD.

SGLT2 initiation actually had a protective effect, compared with dipeptidyl peptidase-4 inhibitors, with a 23% decreased risk of the composite outcome (6.5 fewer events) among patients both with and without baseline CVD. The findings were all statistically significant.

The average age in the study was 71.5 years; 45% of the subjects were men; 40% had a history of cardiovascular disease; and 60% were on metformin and 24% on insulin at study entry.

The work was funded by the National Institutes of Health. Dr. Patorno disclosed research grants form Boehringer Ingelheim and GlaxoSmithKline. Other investigators reported relationships with numerous pharmaceutical companies.

[email protected]

SAN FRANCISCO – A large, long-term study is linking yet another glucagon-like peptide–1 receptor agonist diabetes drug to positive cardiovascular outcomes: Patients with type 2 diabetes and heart disease risk factors who took dulaglutide for about 5 years during the REWIND study had a 12% lower risk of major adverse cardiovascular events, compared with those who took placebo.

These new findings on cardiac risk are unusual compared with other newer-generation diabetes drugs, because a high percentage of the participants did not have existing cardiovascular disease. In addition, the study population had a higher percentage of women, compared with previous studies.

“We feel very strongly that the participants were similar to the ... ambulatory patients with type 2 diabetes with cardiovascular risk who are routinely seen in clinical practice,” study coauthor Jeffrey L. Probstfield, MD, of the University of Washington, Seattle, saidin a presentation at the annual scientific sessions of the American Diabetes Association. The findings were published simultaneously in The Lancet (2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

Dulaglutide’s serious adverse-effect profile was similar to that of placebo, the study authors noted, and the drug also showed benefits in renal outcomes, as reported in a separate study (Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31150-3.

The Food and Drug Administration has mandated that six glucagon-like peptide–1 receptor agonists (GLP-1 RAs) – albiglutide (Tanzeum), exenatide (Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), semaglutide (Ozempic) and dulaglutide (Trulicity) – undergo testing of cardiovascular outcomes. Dulaglutide is the fourth, following albiglutide, liraglutide, and semaglutide, to show consistent, statistically significant reduction in major adverse cardiovascular events (MACE).

For the double-blind, randomized, placebo-controlled REWIND study, researchers recruited 9,901 participants who were at least 50 years old with type 2 diabetes, a hemoglobin A_1c (HbA_1c) level of 9.5% or less, and a body mass index of more than 23 kg/m². The participants came from 371 sites in 24 countries, including the United States and Canada. More than 80% were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and other blood pressure drugs were also common.

The average mean age was 66 years; 46% of the participants were women, three-quarters were white, and 31% had previous cardiovascular disease. Previous GLP-1 RA studies of this type had markedly lower percentages of women – the other studies comprised 30%-39% women – and included higher percentages of participants with previous cardiovascular disease (73%-100%).

Of the participants in the current study, 4,949 were assigned to receive dulaglutide and 4,952 to receive placebo. They were followed for a median 5.4 years. About 57% never stopped using the drug, and 11% of those in the drug group and 7.5% in the placebo group stopped use because of adverse effects.

In regard to diabetes outcomes, HbA_1c levels fell in the drug group by a mean –0.61% (95% confidence interval, –0.65 to –0.58; P less than .0001), compared with placebo. Their weight decreased by a mean –1.5 kg (95% CI, -1.7 to -1.3; P less than .0001) Systolic blood pressure and LDL cholesterol levels were slightly lower in the drug group, but heart rate was higher.

On the heart front, MACE fell by 12% in the drug group, compared with placebo (hazard ratio, 0.88; 95% CI, 0.79-0.99; P = .026). “The effect of the intervention begins [within] the first year and continued in a progressive, proportional fashion throughout the follow-up period,” said study lead author Hertzel C. Gerstein, MD, of McMaster University and Hamilton Health Sciences, Hamilton, Ont.

However, she called attention to the results that pinpointed higher levels of microvascular-related eye outcomes (HR, 1.24; 95% CI, 0.92-1.68) and fatal myocardial infarction (HR, 1.29; 95% CI, 0.72-2.30) in the dulaglutide group. Both of those outcomes were rare – 171 eye outcomes and 46 fatal myocardial infarctions overall. She also questioned whether the adherence rates would be as high in a real-world setting.

Eli Lilly funded the study. Three of the authors were employees of Eli Lilly, eight reported financial relationships with the company, five reported financial relationships with other firms, and the remaining authors reported no competing interests.

SOURCE: Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

SAN FRANCISCO – A large, long-term study is linking yet another glucagon-like peptide–1 receptor agonist diabetes drug to positive cardiovascular outcomes: Patients with type 2 diabetes and heart disease risk factors who took dulaglutide for about 5 years during the REWIND study had a 12% lower risk of major adverse cardiovascular events, compared with those who took placebo.

These new findings on cardiac risk are unusual compared with other newer-generation diabetes drugs, because a high percentage of the participants did not have existing cardiovascular disease. In addition, the study population had a higher percentage of women, compared with previous studies.

“We feel very strongly that the participants were similar to the ... ambulatory patients with type 2 diabetes with cardiovascular risk who are routinely seen in clinical practice,” study coauthor Jeffrey L. Probstfield, MD, of the University of Washington, Seattle, saidin a presentation at the annual scientific sessions of the American Diabetes Association. The findings were published simultaneously in The Lancet (2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

Dulaglutide’s serious adverse-effect profile was similar to that of placebo, the study authors noted, and the drug also showed benefits in renal outcomes, as reported in a separate study (Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31150-3.

The Food and Drug Administration has mandated that six glucagon-like peptide–1 receptor agonists (GLP-1 RAs) – albiglutide (Tanzeum), exenatide (Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), semaglutide (Ozempic) and dulaglutide (Trulicity) – undergo testing of cardiovascular outcomes. Dulaglutide is the fourth, following albiglutide, liraglutide, and semaglutide, to show consistent, statistically significant reduction in major adverse cardiovascular events (MACE).

For the double-blind, randomized, placebo-controlled REWIND study, researchers recruited 9,901 participants who were at least 50 years old with type 2 diabetes, a hemoglobin A_1c (HbA_1c) level of 9.5% or less, and a body mass index of more than 23 kg/m². The participants came from 371 sites in 24 countries, including the United States and Canada. More than 80% were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and other blood pressure drugs were also common.

The average mean age was 66 years; 46% of the participants were women, three-quarters were white, and 31% had previous cardiovascular disease. Previous GLP-1 RA studies of this type had markedly lower percentages of women – the other studies comprised 30%-39% women – and included higher percentages of participants with previous cardiovascular disease (73%-100%).

Of the participants in the current study, 4,949 were assigned to receive dulaglutide and 4,952 to receive placebo. They were followed for a median 5.4 years. About 57% never stopped using the drug, and 11% of those in the drug group and 7.5% in the placebo group stopped use because of adverse effects.

In regard to diabetes outcomes, HbA_1c levels fell in the drug group by a mean –0.61% (95% confidence interval, –0.65 to –0.58; P less than .0001), compared with placebo. Their weight decreased by a mean –1.5 kg (95% CI, -1.7 to -1.3; P less than .0001) Systolic blood pressure and LDL cholesterol levels were slightly lower in the drug group, but heart rate was higher.

On the heart front, MACE fell by 12% in the drug group, compared with placebo (hazard ratio, 0.88; 95% CI, 0.79-0.99; P = .026). “The effect of the intervention begins [within] the first year and continued in a progressive, proportional fashion throughout the follow-up period,” said study lead author Hertzel C. Gerstein, MD, of McMaster University and Hamilton Health Sciences, Hamilton, Ont.

However, she called attention to the results that pinpointed higher levels of microvascular-related eye outcomes (HR, 1.24; 95% CI, 0.92-1.68) and fatal myocardial infarction (HR, 1.29; 95% CI, 0.72-2.30) in the dulaglutide group. Both of those outcomes were rare – 171 eye outcomes and 46 fatal myocardial infarctions overall. She also questioned whether the adherence rates would be as high in a real-world setting.

Eli Lilly funded the study. Three of the authors were employees of Eli Lilly, eight reported financial relationships with the company, five reported financial relationships with other firms, and the remaining authors reported no competing interests.

SOURCE: Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

SAN FRANCISCO – A large, long-term study is linking yet another glucagon-like peptide–1 receptor agonist diabetes drug to positive cardiovascular outcomes: Patients with type 2 diabetes and heart disease risk factors who took dulaglutide for about 5 years during the REWIND study had a 12% lower risk of major adverse cardiovascular events, compared with those who took placebo.

These new findings on cardiac risk are unusual compared with other newer-generation diabetes drugs, because a high percentage of the participants did not have existing cardiovascular disease. In addition, the study population had a higher percentage of women, compared with previous studies.

“We feel very strongly that the participants were similar to the ... ambulatory patients with type 2 diabetes with cardiovascular risk who are routinely seen in clinical practice,” study coauthor Jeffrey L. Probstfield, MD, of the University of Washington, Seattle, saidin a presentation at the annual scientific sessions of the American Diabetes Association. The findings were published simultaneously in The Lancet (2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

Dulaglutide’s serious adverse-effect profile was similar to that of placebo, the study authors noted, and the drug also showed benefits in renal outcomes, as reported in a separate study (Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31150-3.

The Food and Drug Administration has mandated that six glucagon-like peptide–1 receptor agonists (GLP-1 RAs) – albiglutide (Tanzeum), exenatide (Byetta), liraglutide (Victoza), lixisenatide (Adlyxin), semaglutide (Ozempic) and dulaglutide (Trulicity) – undergo testing of cardiovascular outcomes. Dulaglutide is the fourth, following albiglutide, liraglutide, and semaglutide, to show consistent, statistically significant reduction in major adverse cardiovascular events (MACE).

For the double-blind, randomized, placebo-controlled REWIND study, researchers recruited 9,901 participants who were at least 50 years old with type 2 diabetes, a hemoglobin A_1c (HbA_1c) level of 9.5% or less, and a body mass index of more than 23 kg/m². The participants came from 371 sites in 24 countries, including the United States and Canada. More than 80% were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and other blood pressure drugs were also common.

The average mean age was 66 years; 46% of the participants were women, three-quarters were white, and 31% had previous cardiovascular disease. Previous GLP-1 RA studies of this type had markedly lower percentages of women – the other studies comprised 30%-39% women – and included higher percentages of participants with previous cardiovascular disease (73%-100%).

Of the participants in the current study, 4,949 were assigned to receive dulaglutide and 4,952 to receive placebo. They were followed for a median 5.4 years. About 57% never stopped using the drug, and 11% of those in the drug group and 7.5% in the placebo group stopped use because of adverse effects.

In regard to diabetes outcomes, HbA_1c levels fell in the drug group by a mean –0.61% (95% confidence interval, –0.65 to –0.58; P less than .0001), compared with placebo. Their weight decreased by a mean –1.5 kg (95% CI, -1.7 to -1.3; P less than .0001) Systolic blood pressure and LDL cholesterol levels were slightly lower in the drug group, but heart rate was higher.

On the heart front, MACE fell by 12% in the drug group, compared with placebo (hazard ratio, 0.88; 95% CI, 0.79-0.99; P = .026). “The effect of the intervention begins [within] the first year and continued in a progressive, proportional fashion throughout the follow-up period,” said study lead author Hertzel C. Gerstein, MD, of McMaster University and Hamilton Health Sciences, Hamilton, Ont.

However, she called attention to the results that pinpointed higher levels of microvascular-related eye outcomes (HR, 1.24; 95% CI, 0.92-1.68) and fatal myocardial infarction (HR, 1.29; 95% CI, 0.72-2.30) in the dulaglutide group. Both of those outcomes were rare – 171 eye outcomes and 46 fatal myocardial infarctions overall. She also questioned whether the adherence rates would be as high in a real-world setting.

Eli Lilly funded the study. Three of the authors were employees of Eli Lilly, eight reported financial relationships with the company, five reported financial relationships with other firms, and the remaining authors reported no competing interests.

SOURCE: Gerstein HC et al. Lancet. 2019 Jun 10. doi: 10.1016/S0140-6736(19)31149-3.

Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.

“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.

The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.


This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.

The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).

As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.

The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).

The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.

The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.

The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.

Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.

[email protected]

On Twitter @mitchelzoler

SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.




 

Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.

“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.

The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.


This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.

The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).

As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.

The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).

The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.

The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.

The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.

Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.

[email protected]

On Twitter @mitchelzoler

SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.




 

Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.

“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.

The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.


This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.

The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).

As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.

The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).

The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.

The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.

The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.

Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.

[email protected]

On Twitter @mitchelzoler

SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.




 

SAN FRANCISCO – Seventy-percent of type 2 diabetes patients who lost more than 33 pounds on a liquid diet over a few months, and kept it off, were free of the disease at 2 years, according to United Kingdom investigators.

M. Alexander Otto/MDedge News

The odds of remission – meaning a hemoglobin A1c below 6.5% on repeat testing, off all medications – were directly related to the amount of weight patients lost; 60% of subjects who lost 22-33 pounds were free of type 2 disease at 2 years, versus 29% who lost 11-21 pounds, and 5% who lost less than 11 pounds.

“If people lose” around 30 pounds “and keep it off for 2 years, there’s a two-thirds chance of them escaping type 2 [diabetes]. People want to understand their options, and this is an option. This is very good news for people with diabetes,” said senior investigator Roy Taylor, MD, a professor of medicine and metabolism at the University of Newcastle, Newcastle upon Tyne, England, who presented the findings of the Diabetes Remission Clinical Trial (DiRECT) at the annual scientific sessions of the American Diabetes Association (Lancet Diabetes Endocrinol. 2019 May;7(5):344-355).

A subgroup analysis he also presented found that beta cell function rebounds rapidly after weight loss and is pretty much normal at 2 years, so long as people keep the weight off.


The study is rooted in previous work by Dr. Taylor and his colleagues that found that very low-calorie diets normalized fasting plasma glucose in just 7 days in patients with type 2 diabetes due to a rapid fall in liver fat content and subsequent restoration of insulin sensitivity. That and other findings suggested that fast weight loss – instead of the traditional gradual approach – might help.

He and his team randomized 149 volunteers from primary care practices in the United Kingdom to standard care, and 149 others to rapid weight loss; more than a quarter of the patients who were asked agreed to participate.

[email protected]
 

SOURCE: Zhyzhneuskaya SV et al., ADA 2019 abstract 66-OR

SAN FRANCISCO – Seventy-percent of type 2 diabetes patients who lost more than 33 pounds on a liquid diet over a few months, and kept it off, were free of the disease at 2 years, according to United Kingdom investigators.

M. Alexander Otto/MDedge News

The odds of remission – meaning a hemoglobin A1c below 6.5% on repeat testing, off all medications – were directly related to the amount of weight patients lost; 60% of subjects who lost 22-33 pounds were free of type 2 disease at 2 years, versus 29% who lost 11-21 pounds, and 5% who lost less than 11 pounds.

“If people lose” around 30 pounds “and keep it off for 2 years, there’s a two-thirds chance of them escaping type 2 [diabetes]. People want to understand their options, and this is an option. This is very good news for people with diabetes,” said senior investigator Roy Taylor, MD, a professor of medicine and metabolism at the University of Newcastle, Newcastle upon Tyne, England, who presented the findings of the Diabetes Remission Clinical Trial (DiRECT) at the annual scientific sessions of the American Diabetes Association (Lancet Diabetes Endocrinol. 2019 May;7(5):344-355).

A subgroup analysis he also presented found that beta cell function rebounds rapidly after weight loss and is pretty much normal at 2 years, so long as people keep the weight off.


The study is rooted in previous work by Dr. Taylor and his colleagues that found that very low-calorie diets normalized fasting plasma glucose in just 7 days in patients with type 2 diabetes due to a rapid fall in liver fat content and subsequent restoration of insulin sensitivity. That and other findings suggested that fast weight loss – instead of the traditional gradual approach – might help.

He and his team randomized 149 volunteers from primary care practices in the United Kingdom to standard care, and 149 others to rapid weight loss; more than a quarter of the patients who were asked agreed to participate.

[email protected]
 

SOURCE: Zhyzhneuskaya SV et al., ADA 2019 abstract 66-OR

SAN FRANCISCO – Seventy-percent of type 2 diabetes patients who lost more than 33 pounds on a liquid diet over a few months, and kept it off, were free of the disease at 2 years, according to United Kingdom investigators.

M. Alexander Otto/MDedge News

The odds of remission – meaning a hemoglobin A1c below 6.5% on repeat testing, off all medications – were directly related to the amount of weight patients lost; 60% of subjects who lost 22-33 pounds were free of type 2 disease at 2 years, versus 29% who lost 11-21 pounds, and 5% who lost less than 11 pounds.

“If people lose” around 30 pounds “and keep it off for 2 years, there’s a two-thirds chance of them escaping type 2 [diabetes]. People want to understand their options, and this is an option. This is very good news for people with diabetes,” said senior investigator Roy Taylor, MD, a professor of medicine and metabolism at the University of Newcastle, Newcastle upon Tyne, England, who presented the findings of the Diabetes Remission Clinical Trial (DiRECT) at the annual scientific sessions of the American Diabetes Association (Lancet Diabetes Endocrinol. 2019 May;7(5):344-355).

A subgroup analysis he also presented found that beta cell function rebounds rapidly after weight loss and is pretty much normal at 2 years, so long as people keep the weight off.


The study is rooted in previous work by Dr. Taylor and his colleagues that found that very low-calorie diets normalized fasting plasma glucose in just 7 days in patients with type 2 diabetes due to a rapid fall in liver fat content and subsequent restoration of insulin sensitivity. That and other findings suggested that fast weight loss – instead of the traditional gradual approach – might help.

He and his team randomized 149 volunteers from primary care practices in the United Kingdom to standard care, and 149 others to rapid weight loss; more than a quarter of the patients who were asked agreed to participate.

[email protected]
 

SOURCE: Zhyzhneuskaya SV et al., ADA 2019 abstract 66-OR

Subclinical atherosclerosis in the carotid arteries as measured by ultrasound appears to nearly triple the risk of a first cardiovascular event among patients with psoriatic disease, according to findings from a retrospective study.

pixologicstudio/Thinkstock.com

When added to the Framingham risk score, the measurement significantly improved its predictive ability, Curtis Sobchak, MD, and colleagues wrote in Arthritis & Rheumatology.

The findings indicate that carotid ultrasound could be a useful addition to cardiovascular risk stratification among these patients.

“Traditional algorithms do not consider other factors that may contribute to increased cardiovascular risk in rheumatic disease patients and tend to underestimate cardiovascular risk,” wrote Dr. Sobchak of the University of Toronto and coauthors.

“The advantage of ultrasound over other modalities for vascular imaging includes lack of radiation, low cost of the examination, and its widespread use in rheumatology for joint evaluation. Thus, this assessment could potentially be performed ‘at the bedside’ during consultation to provide immediate valuable information to complement clinical data from history, physical examination, and laboratory data,” they added.

The study retrospectively examined a prospective, observational cohort of 559 patients with psoriasis alone or psoriasis and psoriatic arthritis enrolled in the University of Toronto Psoriatic Disease Program. The investigators evaluated five ultrasound measures of atherosclerosis, including total plaque area (TPA), mean carotid intima-media thickness (cIMT), maximal cIMT, plaque category, and TPA category. Then they analyzed the risk relationship with major cardiovascular events (CVEs) classified as myocardial infarction, unstable angina, ischemic stroke, revascularization procedures, or cardiovascular-related death. Minor CVEs included stable angina, exacerbation of congestive heart failure, and transient ischemic attack over a mean follow-up close to 4 years.

The mean baseline TPA was 0.18 cm² and mean cIMT was 639 mcm. Most patients had plaques, including 27.0% with unilateral and 31.5% with bilateral plaques.

The rate of a first CVE during the study period was 1.11 per 100 patient-years, and the rate of a first major CVE was 0.91 per 100 patient-years. The risk of each was significantly related to a higher baseline burden of atherosclerosis.

A multivariate analysis determined that increased TPA at baseline increased the risk of an event by nearly 200% (hazard ratio, 2.85). Mean cIMT was not an independent predictor in the final analysis, “suggesting that TPA is a stronger predictor for CVE than cIMT,” the authors wrote.

Finally, they examined the predictive value of atherosclerosis alone, as well as combined with the Framingham risk score. The 5-year model indicated that the bivariate model was slightly more accurate than the Framingham score alone (area under the curve, 0.84 vs. 0.81), although this was not a significant difference. The predictive value of the Framingham risk score plus maximal cIMT, mean cIMT, or TPA all significantly improved when they were calculated using only high-risk patients (those above the treatment threshold for dyslipidemia).

“To the best of our knowledge this is the first study to assess the utility of various measures of carotid atherosclerosis to predict CVE in patients with psoriasis and PsA [psoriatic arthritis]. ... Combining vascular imaging data with clinical and laboratory measures of traditional cardiovascular risk factors could improve accuracy of cardiovascular risk stratification in patients with psoriatic disease and facilitate earlier initiation of appropriate treatment to reduce CVE in this population,” the investigators wrote.

The study was supported in part by a Young Investigator Operating Grant from the Arthritis Society. Dr. Sobchak had no financial disclosures.

[email protected]

SOURCE: Sobchak C et al. Arthritis Rheumatol. 2019 Jun 5. doi: 10.1002/art.40925.

Subclinical atherosclerosis in the carotid arteries as measured by ultrasound appears to nearly triple the risk of a first cardiovascular event among patients with psoriatic disease, according to findings from a retrospective study.

pixologicstudio/Thinkstock.com

When added to the Framingham risk score, the measurement significantly improved its predictive ability, Curtis Sobchak, MD, and colleagues wrote in Arthritis & Rheumatology.

The findings indicate that carotid ultrasound could be a useful addition to cardiovascular risk stratification among these patients.

“Traditional algorithms do not consider other factors that may contribute to increased cardiovascular risk in rheumatic disease patients and tend to underestimate cardiovascular risk,” wrote Dr. Sobchak of the University of Toronto and coauthors.

“The advantage of ultrasound over other modalities for vascular imaging includes lack of radiation, low cost of the examination, and its widespread use in rheumatology for joint evaluation. Thus, this assessment could potentially be performed ‘at the bedside’ during consultation to provide immediate valuable information to complement clinical data from history, physical examination, and laboratory data,” they added.

The study retrospectively examined a prospective, observational cohort of 559 patients with psoriasis alone or psoriasis and psoriatic arthritis enrolled in the University of Toronto Psoriatic Disease Program. The investigators evaluated five ultrasound measures of atherosclerosis, including total plaque area (TPA), mean carotid intima-media thickness (cIMT), maximal cIMT, plaque category, and TPA category. Then they analyzed the risk relationship with major cardiovascular events (CVEs) classified as myocardial infarction, unstable angina, ischemic stroke, revascularization procedures, or cardiovascular-related death. Minor CVEs included stable angina, exacerbation of congestive heart failure, and transient ischemic attack over a mean follow-up close to 4 years.

The mean baseline TPA was 0.18 cm² and mean cIMT was 639 mcm. Most patients had plaques, including 27.0% with unilateral and 31.5% with bilateral plaques.

The rate of a first CVE during the study period was 1.11 per 100 patient-years, and the rate of a first major CVE was 0.91 per 100 patient-years. The risk of each was significantly related to a higher baseline burden of atherosclerosis.

A multivariate analysis determined that increased TPA at baseline increased the risk of an event by nearly 200% (hazard ratio, 2.85). Mean cIMT was not an independent predictor in the final analysis, “suggesting that TPA is a stronger predictor for CVE than cIMT,” the authors wrote.

Finally, they examined the predictive value of atherosclerosis alone, as well as combined with the Framingham risk score. The 5-year model indicated that the bivariate model was slightly more accurate than the Framingham score alone (area under the curve, 0.84 vs. 0.81), although this was not a significant difference. The predictive value of the Framingham risk score plus maximal cIMT, mean cIMT, or TPA all significantly improved when they were calculated using only high-risk patients (those above the treatment threshold for dyslipidemia).

“To the best of our knowledge this is the first study to assess the utility of various measures of carotid atherosclerosis to predict CVE in patients with psoriasis and PsA [psoriatic arthritis]. ... Combining vascular imaging data with clinical and laboratory measures of traditional cardiovascular risk factors could improve accuracy of cardiovascular risk stratification in patients with psoriatic disease and facilitate earlier initiation of appropriate treatment to reduce CVE in this population,” the investigators wrote.

The study was supported in part by a Young Investigator Operating Grant from the Arthritis Society. Dr. Sobchak had no financial disclosures.

[email protected]

SOURCE: Sobchak C et al. Arthritis Rheumatol. 2019 Jun 5. doi: 10.1002/art.40925.

Subclinical atherosclerosis in the carotid arteries as measured by ultrasound appears to nearly triple the risk of a first cardiovascular event among patients with psoriatic disease, according to findings from a retrospective study.

pixologicstudio/Thinkstock.com

When added to the Framingham risk score, the measurement significantly improved its predictive ability, Curtis Sobchak, MD, and colleagues wrote in Arthritis & Rheumatology.

The findings indicate that carotid ultrasound could be a useful addition to cardiovascular risk stratification among these patients.

“Traditional algorithms do not consider other factors that may contribute to increased cardiovascular risk in rheumatic disease patients and tend to underestimate cardiovascular risk,” wrote Dr. Sobchak of the University of Toronto and coauthors.

“The advantage of ultrasound over other modalities for vascular imaging includes lack of radiation, low cost of the examination, and its widespread use in rheumatology for joint evaluation. Thus, this assessment could potentially be performed ‘at the bedside’ during consultation to provide immediate valuable information to complement clinical data from history, physical examination, and laboratory data,” they added.

The study retrospectively examined a prospective, observational cohort of 559 patients with psoriasis alone or psoriasis and psoriatic arthritis enrolled in the University of Toronto Psoriatic Disease Program. The investigators evaluated five ultrasound measures of atherosclerosis, including total plaque area (TPA), mean carotid intima-media thickness (cIMT), maximal cIMT, plaque category, and TPA category. Then they analyzed the risk relationship with major cardiovascular events (CVEs) classified as myocardial infarction, unstable angina, ischemic stroke, revascularization procedures, or cardiovascular-related death. Minor CVEs included stable angina, exacerbation of congestive heart failure, and transient ischemic attack over a mean follow-up close to 4 years.

The mean baseline TPA was 0.18 cm² and mean cIMT was 639 mcm. Most patients had plaques, including 27.0% with unilateral and 31.5% with bilateral plaques.

The rate of a first CVE during the study period was 1.11 per 100 patient-years, and the rate of a first major CVE was 0.91 per 100 patient-years. The risk of each was significantly related to a higher baseline burden of atherosclerosis.

A multivariate analysis determined that increased TPA at baseline increased the risk of an event by nearly 200% (hazard ratio, 2.85). Mean cIMT was not an independent predictor in the final analysis, “suggesting that TPA is a stronger predictor for CVE than cIMT,” the authors wrote.

Finally, they examined the predictive value of atherosclerosis alone, as well as combined with the Framingham risk score. The 5-year model indicated that the bivariate model was slightly more accurate than the Framingham score alone (area under the curve, 0.84 vs. 0.81), although this was not a significant difference. The predictive value of the Framingham risk score plus maximal cIMT, mean cIMT, or TPA all significantly improved when they were calculated using only high-risk patients (those above the treatment threshold for dyslipidemia).

“To the best of our knowledge this is the first study to assess the utility of various measures of carotid atherosclerosis to predict CVE in patients with psoriasis and PsA [psoriatic arthritis]. ... Combining vascular imaging data with clinical and laboratory measures of traditional cardiovascular risk factors could improve accuracy of cardiovascular risk stratification in patients with psoriatic disease and facilitate earlier initiation of appropriate treatment to reduce CVE in this population,” the investigators wrote.

The study was supported in part by a Young Investigator Operating Grant from the Arthritis Society. Dr. Sobchak had no financial disclosures.

[email protected]

SOURCE: Sobchak C et al. Arthritis Rheumatol. 2019 Jun 5. doi: 10.1002/art.40925.

Lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease–related events, and plasma levels of Lp(a) could help refine risk assessment and influence treatment decisions, say the authors of a scientific statement from the National Lipid Association.

Don P. Wilson, MD, of Cook Children’s Medical Center, Fort Worth, Tex., and coauthors reviewed the evidence around testing of Lp(a) in clinical practice and its use in guiding treatment for both primary and secondary prevention. Their report is in the Journal of Clinical Lipidology.

Prospective, population-based studies point to a clear link between high Lp(a) levels and high risk of myocardial infarction, coronary heart disease, coronary artery stenosis, carotid stenosis, valvular aortic stenosis, ischemic stroke, cardiovascular mortality, and all-cause mortality, the authors wrote. This association was independent of the effect of other risk factors, including LDL cholesterol.

However, existing Lp(a) assays have not been globally standardized, and there is only incomplete evidence for age, sex, or ethnicity-specific cutoff points for high risk.

The authors suggested Lp(a) levels greater than 50 mg/dL (100 nmol/L) could be considered a risk factor that justifies the initiation of statin therapy. However ,they pointed out this level corresponded to the 80th population percentile in predominantly white populations, while in African American populations the equivalent cutoff was around 150 nmol/L.

On the issue of whom to test for Lp(a) serum levels, the authors said testing could reasonably be used to refine risk assessment for atherosclerotic cardiovascular disease in adults with first-degree relatives who experienced premature atherosclerotic cardiovascular disease, those with a personal history of the disease, or in those with severe hypercholesterolemia or suspected familial hypercholesterolemia.

However, statin therapy does not decrease Lp(a) levels, and there is also evidence that patients with high Lp(a) levels may not show as much LDL-C lowering in response to statin therapy.

“There is a lack of current evidence demonstrating that lowering Lp(a), independently of LDL-C, reduces ASCVD events in individuals with established ASCVD,” the authors wrote. “It appears that large absolute reductions in Lp(a) may be needed to demonstrate a significant clinical benefit.”

Despite this, the authors argued that in primary prevention, it was reasonable to use a Lp(a) level greater than 50 mg/dL (100 nmol/L) as a “risk-enhancing factor,” and in high-risk or very-high-risk patients with elevated LDL-C, it could prompt use of more intensive therapies.

Five authors disclosed honorarium or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Clin Lipidol. 2019 May 17. doi: 10.1016/j.jacl.2019.04.010.

Lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease–related events, and plasma levels of Lp(a) could help refine risk assessment and influence treatment decisions, say the authors of a scientific statement from the National Lipid Association.

Don P. Wilson, MD, of Cook Children’s Medical Center, Fort Worth, Tex., and coauthors reviewed the evidence around testing of Lp(a) in clinical practice and its use in guiding treatment for both primary and secondary prevention. Their report is in the Journal of Clinical Lipidology.

Prospective, population-based studies point to a clear link between high Lp(a) levels and high risk of myocardial infarction, coronary heart disease, coronary artery stenosis, carotid stenosis, valvular aortic stenosis, ischemic stroke, cardiovascular mortality, and all-cause mortality, the authors wrote. This association was independent of the effect of other risk factors, including LDL cholesterol.

However, existing Lp(a) assays have not been globally standardized, and there is only incomplete evidence for age, sex, or ethnicity-specific cutoff points for high risk.

The authors suggested Lp(a) levels greater than 50 mg/dL (100 nmol/L) could be considered a risk factor that justifies the initiation of statin therapy. However ,they pointed out this level corresponded to the 80th population percentile in predominantly white populations, while in African American populations the equivalent cutoff was around 150 nmol/L.

On the issue of whom to test for Lp(a) serum levels, the authors said testing could reasonably be used to refine risk assessment for atherosclerotic cardiovascular disease in adults with first-degree relatives who experienced premature atherosclerotic cardiovascular disease, those with a personal history of the disease, or in those with severe hypercholesterolemia or suspected familial hypercholesterolemia.

However, statin therapy does not decrease Lp(a) levels, and there is also evidence that patients with high Lp(a) levels may not show as much LDL-C lowering in response to statin therapy.

“There is a lack of current evidence demonstrating that lowering Lp(a), independently of LDL-C, reduces ASCVD events in individuals with established ASCVD,” the authors wrote. “It appears that large absolute reductions in Lp(a) may be needed to demonstrate a significant clinical benefit.”

Despite this, the authors argued that in primary prevention, it was reasonable to use a Lp(a) level greater than 50 mg/dL (100 nmol/L) as a “risk-enhancing factor,” and in high-risk or very-high-risk patients with elevated LDL-C, it could prompt use of more intensive therapies.

Five authors disclosed honorarium or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Clin Lipidol. 2019 May 17. doi: 10.1016/j.jacl.2019.04.010.

Lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease–related events, and plasma levels of Lp(a) could help refine risk assessment and influence treatment decisions, say the authors of a scientific statement from the National Lipid Association.

Don P. Wilson, MD, of Cook Children’s Medical Center, Fort Worth, Tex., and coauthors reviewed the evidence around testing of Lp(a) in clinical practice and its use in guiding treatment for both primary and secondary prevention. Their report is in the Journal of Clinical Lipidology.

Prospective, population-based studies point to a clear link between high Lp(a) levels and high risk of myocardial infarction, coronary heart disease, coronary artery stenosis, carotid stenosis, valvular aortic stenosis, ischemic stroke, cardiovascular mortality, and all-cause mortality, the authors wrote. This association was independent of the effect of other risk factors, including LDL cholesterol.

However, existing Lp(a) assays have not been globally standardized, and there is only incomplete evidence for age, sex, or ethnicity-specific cutoff points for high risk.

The authors suggested Lp(a) levels greater than 50 mg/dL (100 nmol/L) could be considered a risk factor that justifies the initiation of statin therapy. However ,they pointed out this level corresponded to the 80th population percentile in predominantly white populations, while in African American populations the equivalent cutoff was around 150 nmol/L.

On the issue of whom to test for Lp(a) serum levels, the authors said testing could reasonably be used to refine risk assessment for atherosclerotic cardiovascular disease in adults with first-degree relatives who experienced premature atherosclerotic cardiovascular disease, those with a personal history of the disease, or in those with severe hypercholesterolemia or suspected familial hypercholesterolemia.

However, statin therapy does not decrease Lp(a) levels, and there is also evidence that patients with high Lp(a) levels may not show as much LDL-C lowering in response to statin therapy.

“There is a lack of current evidence demonstrating that lowering Lp(a), independently of LDL-C, reduces ASCVD events in individuals with established ASCVD,” the authors wrote. “It appears that large absolute reductions in Lp(a) may be needed to demonstrate a significant clinical benefit.”

Despite this, the authors argued that in primary prevention, it was reasonable to use a Lp(a) level greater than 50 mg/dL (100 nmol/L) as a “risk-enhancing factor,” and in high-risk or very-high-risk patients with elevated LDL-C, it could prompt use of more intensive therapies.

Five authors disclosed honorarium or advisory board positions with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Clin Lipidol. 2019 May 17. doi: 10.1016/j.jacl.2019.04.010.

The Food and Drug Administration has granted a Priority Review to the supplemental new drug application for icosapent ethyl (Vascepa).

Wikimedia Commons/FitzColinGerald/Creative Commons License

If approved, Vascepa – which is produced by Amarin – would be the first drug indicated to reduce residual cardiovascular risk in patients with LDL cholesterol managed by statins who still have persistent elevated triglycerides. The drug is now approved for reducing triglyceride levels in patients with baseline values of 500 mg/dL or greater.

The Priority Review is based on results of REDUCE-IT, a landmark cardiovascular outcomes trial whose primary results were presented at the American Heart Association scientific sessions last November and published in the New England Journal of Medicine. Vascepa achieved the primary study endpoint, reducing the relative risk for the first occurrence of a major adverse cardiovascular event significantly, by 25%.

The drug also met the study’s key secondary endpoint, reducing the incidence of a composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke by 26%. Significant adverse events associated with Vascepa in the trial were peripheral edema, constipation, and atrial fibrillation.

Vascepa is currently indicated as an adjunct to diet to reduce triglyceride in adults with severe hypertriglyceridemia, a significantly smaller population than that represented in REDUCE-IT.

“We expect earlier approval of an expanded indication for Vascepa to lead to faster improvements in care for millions of patients with residual cardiovascular risk after statin therapy,” John F. Thero, president and CEO of Amarin, said in the statement.

The FDA is expected to issue a complete response by the end of September. Find the full press release on the Amarin website.

[email protected]

The Food and Drug Administration has granted a Priority Review to the supplemental new drug application for icosapent ethyl (Vascepa).

Wikimedia Commons/FitzColinGerald/Creative Commons License

If approved, Vascepa – which is produced by Amarin – would be the first drug indicated to reduce residual cardiovascular risk in patients with LDL cholesterol managed by statins who still have persistent elevated triglycerides. The drug is now approved for reducing triglyceride levels in patients with baseline values of 500 mg/dL or greater.

The Priority Review is based on results of REDUCE-IT, a landmark cardiovascular outcomes trial whose primary results were presented at the American Heart Association scientific sessions last November and published in the New England Journal of Medicine. Vascepa achieved the primary study endpoint, reducing the relative risk for the first occurrence of a major adverse cardiovascular event significantly, by 25%.

The drug also met the study’s key secondary endpoint, reducing the incidence of a composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke by 26%. Significant adverse events associated with Vascepa in the trial were peripheral edema, constipation, and atrial fibrillation.

Vascepa is currently indicated as an adjunct to diet to reduce triglyceride in adults with severe hypertriglyceridemia, a significantly smaller population than that represented in REDUCE-IT.

“We expect earlier approval of an expanded indication for Vascepa to lead to faster improvements in care for millions of patients with residual cardiovascular risk after statin therapy,” John F. Thero, president and CEO of Amarin, said in the statement.

The FDA is expected to issue a complete response by the end of September. Find the full press release on the Amarin website.

[email protected]

The Food and Drug Administration has granted a Priority Review to the supplemental new drug application for icosapent ethyl (Vascepa).

Wikimedia Commons/FitzColinGerald/Creative Commons License

If approved, Vascepa – which is produced by Amarin – would be the first drug indicated to reduce residual cardiovascular risk in patients with LDL cholesterol managed by statins who still have persistent elevated triglycerides. The drug is now approved for reducing triglyceride levels in patients with baseline values of 500 mg/dL or greater.

The Priority Review is based on results of REDUCE-IT, a landmark cardiovascular outcomes trial whose primary results were presented at the American Heart Association scientific sessions last November and published in the New England Journal of Medicine. Vascepa achieved the primary study endpoint, reducing the relative risk for the first occurrence of a major adverse cardiovascular event significantly, by 25%.

The drug also met the study’s key secondary endpoint, reducing the incidence of a composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke by 26%. Significant adverse events associated with Vascepa in the trial were peripheral edema, constipation, and atrial fibrillation.

Vascepa is currently indicated as an adjunct to diet to reduce triglyceride in adults with severe hypertriglyceridemia, a significantly smaller population than that represented in REDUCE-IT.

“We expect earlier approval of an expanded indication for Vascepa to lead to faster improvements in care for millions of patients with residual cardiovascular risk after statin therapy,” John F. Thero, president and CEO of Amarin, said in the statement.

The FDA is expected to issue a complete response by the end of September. Find the full press release on the Amarin website.

[email protected]