Cleveland, OH—Pharmacists field concerns nearly every day about possible intolerance to statins. That is not surprising with a drug used by more than 35 million people in the United States.
Due to that and other issues, statin alternatives have been getting much more notice.
A report in the New England Journal of Medicine recently focused on bempedoic acid, an adenosine triphosphate citrate lyase inhibitor that reduces LDL cholesterol levels and is also associated with a low incidence of muscle-related adverse events.
Cleveland Clinic–led researchers pointed out that its effects on cardiovascular outcomes remained uncertain, however. The drug was FDA-approved in 2020 for the treatment of high LDL cholesterol in patients with heterozygous familial hypercholesterolemia or those with atherosclerotic cardiovascular disease.
The study team conducted a double-blind, randomized, placebo-controlled trial. Included were “statin-intolerant” patients who were unable or unwilling to take statins owing to unacceptable adverse effects. They were also diagnosed with or were at high risk for cardiovascular disease.
In the study, 13,970 participants received either 180-mg daily oral bempedoic acid, which was approved by the FDA in 2020, or placebo. Defined as the primary endpoint was a composite of major adverse cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.
With a median duration of follow-up of 40.6 months, the results indicated that the mean LDL cholesterol level at baseline was 139.0 mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg/dL. The researchers pointed out that “the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid,” adding, “The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001).”
The study advised that bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. “The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels,” the study added.
Another study, presented at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology in New Orleans, had important news about MK-0616, an experimental oral proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibitor. The results were simultaneously published in the Journal of the American College of Cardiology.
MK-0616 is one of the first oral PCSK9-inhibitors to be tested in clinical trials; currently, all available PCSK9-inhibitors must be administered subcutaneously. PCSK9-inhibitors are often used concurrently with statins but can be used alone in people who cannot take statins.
The results from the phase II trial, which involved 381 adults with hypercholesterolemia, showed MK-0616 reduced LDL cholesterol by around 60% among people taking 30 mg or 18 mg daily, compared with those taking a placebo.
“This is a highly effective compound that was well tolerated,” said lead author Christie M. Ballantyne, MD, director of the Center for Metabolic Disease Prevention at Baylor. “MK-0616 could offer another potential option. Between this and statins and the other therapies we have, we should be able to basically treat almost everybody in terms of LDL cholesterol.”
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Published March 14, 2023