In the Journals

CLEAR Harmony: Bempedoic acid with statin therapy lowers LDL

Christie M. Ballantyne

Patients with either atherosclerotic CVD, heterozygous familial hypercholesterolemia or both who were assigned bempedoic acid with maximally tolerated statin therapy had significant decreases in LDL levels without a higher incidence of overall adverse events compared with those assigned placebo, according to results from the CLEAR Harmony trial published in The New England Journal of Medicine.

“Our latest study shows that bempedoic acid could be another addition to the arsenal of cholesterol-lowering treatments available to patients,” Kausik K. Ray, MD, MPhil, professor at Imperial College London School of Public Health, said in a press release. “What we have is a new class of drug that could be given to patients who are already taking statins and could help them to further reduce their cholesterol levels and, thus, potentially cut their risk of heart attacks and strokes.”

In this phase 3 trial, researchers analyzed data from 2,230 patients with ASCVD, heterozygous familial hypercholesterolemia or both, were on maximally tolerated statin therapy and had a fasting LDL level of at least 70 mg/dL. Patients were assigned 180 mg once-daily bempedoic acid (Esperion Therapeutics; n = 1,488; mean age, 66 years; 74% men) or placebo (n = 742; mean age, 67 years; 71% men).

The primary endpoint was overall safety, which was determined by changes in safety laboratory variables and the incidence of adverse events. The principal secondary endpoint was the percentage change in LDL from baseline to week 12.

Follow-up visits that included fasting blood samples were conducted at 4, 8, 12, 24, 36 and 52 weeks.

At baseline, the mean LDL level was 103.2 mg/dL for all patients in the study.

The bempedoic acid and placebo groups had similar incidence of adverse events (78.5% vs. 78.7%, respectively) and serious adverse events (14.5% vs. 14%, respectively). Patients assigned bempedoic acid had a higher incidence of adverse events leading to regimen discontinuation compared with those assigned placebo (10.9% vs. 7.1%; P = .005). This was also seen in the incidence of gout (1.2% vs. 0.3%; P = .03).

At 12 weeks, patients assigned bempedoic acid had a mean reduction in LDL of 19.2 mg/dL, which represented a –16.5% change from baseline (difference compared with placebo = –18.1 percentage points; 95% CI, –20 to –16.1).

Findings regarding safety and efficacy were consistent despite background statin therapy intensity.

“Some of the adverse effects, such as increases of uric acid and gout, are problems that health care providers can recognize with routing blood tests and that can be managed,” Christie M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, professor of medicine, chief of the section of cardiovascular research and director of the Center for Cardiovascular Disease Prevention at Baylor College of Medicine, said in a press release. “So the bigger picture is understanding the types of side effects that can develop, whether they can be managed and the benefit of the drug on LDL levels in patients who are at high risk for cardiovascular events and who still have higher levels of LDL-C than are optimal on the highest dose of statin that they can tolerate.” – by Darlene Dobkowski

Disclosure s : The study was funded by Esperion Therapeutics. Ray reports he received personal fees from AbbVie, Akcea, Algorithm, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Cipla, Dr. Reddy’s, Esperion, Kowa, Lilly, Medco, Merck, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Takeda and Zuellig Pharma, and grants from Amgen, Merck, Pfizer, Regeneron and Sanofi. Ballantyne reports he received grants from Akcea, American Diabetes Association, American Heart Association, Amgen, Esperion, NIH, Novartis, Regeneron and Sanofi-Synthelabo and personal fees from Akcea, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Denka Seiken, Esperion, Intercept, Janssen, Matinas BioPharma, Merck, Novartis, Novo Nordisk, Regeneron and Sanofi-Synthelabo. Please see the study for all other authors’ relevant financial disclosures.

 

Christie M. Ballantyne

Patients with either atherosclerotic CVD, heterozygous familial hypercholesterolemia or both who were assigned bempedoic acid with maximally tolerated statin therapy had significant decreases in LDL levels without a higher incidence of overall adverse events compared with those assigned placebo, according to results from the CLEAR Harmony trial published in The New England Journal of Medicine.

“Our latest study shows that bempedoic acid could be another addition to the arsenal of cholesterol-lowering treatments available to patients,” Kausik K. Ray, MD, MPhil, professor at Imperial College London School of Public Health, said in a press release. “What we have is a new class of drug that could be given to patients who are already taking statins and could help them to further reduce their cholesterol levels and, thus, potentially cut their risk of heart attacks and strokes.”

In this phase 3 trial, researchers analyzed data from 2,230 patients with ASCVD, heterozygous familial hypercholesterolemia or both, were on maximally tolerated statin therapy and had a fasting LDL level of at least 70 mg/dL. Patients were assigned 180 mg once-daily bempedoic acid (Esperion Therapeutics; n = 1,488; mean age, 66 years; 74% men) or placebo (n = 742; mean age, 67 years; 71% men).

The primary endpoint was overall safety, which was determined by changes in safety laboratory variables and the incidence of adverse events. The principal secondary endpoint was the percentage change in LDL from baseline to week 12.

Follow-up visits that included fasting blood samples were conducted at 4, 8, 12, 24, 36 and 52 weeks.

At baseline, the mean LDL level was 103.2 mg/dL for all patients in the study.

The bempedoic acid and placebo groups had similar incidence of adverse events (78.5% vs. 78.7%, respectively) and serious adverse events (14.5% vs. 14%, respectively). Patients assigned bempedoic acid had a higher incidence of adverse events leading to regimen discontinuation compared with those assigned placebo (10.9% vs. 7.1%; P = .005). This was also seen in the incidence of gout (1.2% vs. 0.3%; P = .03).

At 12 weeks, patients assigned bempedoic acid had a mean reduction in LDL of 19.2 mg/dL, which represented a –16.5% change from baseline (difference compared with placebo = –18.1 percentage points; 95% CI, –20 to –16.1).

Findings regarding safety and efficacy were consistent despite background statin therapy intensity.

“Some of the adverse effects, such as increases of uric acid and gout, are problems that health care providers can recognize with routing blood tests and that can be managed,” Christie M. Ballantyne, MD, FACC, FACP, FAHA, FNLA, professor of medicine, chief of the section of cardiovascular research and director of the Center for Cardiovascular Disease Prevention at Baylor College of Medicine, said in a press release. “So the bigger picture is understanding the types of side effects that can develop, whether they can be managed and the benefit of the drug on LDL levels in patients who are at high risk for cardiovascular events and who still have higher levels of LDL-C than are optimal on the highest dose of statin that they can tolerate.” – by Darlene Dobkowski

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Disclosure s : The study was funded by Esperion Therapeutics. Ray reports he received personal fees from AbbVie, Akcea, Algorithm, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Cipla, Dr. Reddy’s, Esperion, Kowa, Lilly, Medco, Merck, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Takeda and Zuellig Pharma, and grants from Amgen, Merck, Pfizer, Regeneron and Sanofi. Ballantyne reports he received grants from Akcea, American Diabetes Association, American Heart Association, Amgen, Esperion, NIH, Novartis, Regeneron and Sanofi-Synthelabo and personal fees from Akcea, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Denka Seiken, Esperion, Intercept, Janssen, Matinas BioPharma, Merck, Novartis, Novo Nordisk, Regeneron and Sanofi-Synthelabo. Please see the study for all other authors’ relevant financial disclosures.