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Bempedoic Acid & Cardiovascular Outcomes in Statin-Intolerant Patients

During a median follow-up of 40.6 months, statin-intolerant patients had a 13% reduction in risks of major adverse cardiovascular events when treated with the ATP citrate lyase inhibitor bempedoic acid, a placebo-controlled study shows. “Whether real or perceived, statin intolerance remains a vexing clinical problem that can prevent patients who are guideline-eligible for statin treatment from reaching LDL cholesterol levels associated with clinical benefits,” the CLEAR Outcomes investigators write. “Accordingly, alternative nonstatin therapies are needed to manage the LDL cholesterol level in these patients.”

The double-blind trial randomized 13,970 high-risk participants who were unable or unwilling to take statins because of unacceptable adverse effects and had or were at high risk for cardiovascular disease. The patients were assigned to receive oral bempedoic acid 180 mg daily or placebo.

Based on a primary endpoint was a composite of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization), the study showed: “The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. 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). 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.”

Editorial: “Available data clearly indicate that bempedoic acid can be used as an adjunct to statin and nonstatin therapies (except as noted above) to produce an additional 16 to 26% reduction in the LDL cholesterol level,” writes an editorialist. “However, it is not yet clear to what extent adjunctive bempedoic acid will further reduce the risk of cardiovascular events. This issue can only be addressed with specific trials powered to detect the effect of bempedoic acid on clinical events. However, at least in statin-intolerant patients, data from the CLEAR Outcomes trial indicate that bempedoic acid may reduce both the LDL cholesterol level and the risk of cardiovascular events.”

Source: New England Journal of Medicine