1. In this randomized controlled trial, bempedoic acid significantly reduced low-density lipoprotein (LDL) cholesterol levels in patients with increased cardiovascular risk as compared to placebo.
2. Adverse events that elevated in the bempedoic group included a reduction in renal tubular excretion of uric acid and creatinine as well as incidences of elevated hepatic-enzyme levels and gout.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Statin treatment is the mainstay prevention strategy for adverse cardiovascular events. Up to one-third of patients using statin report unacceptable musculoskeletal side effects. Bempedoic is a prodrug that is activated in the liver with reduced effect in peripheral skeletal muscle, leading to a potentially more favorable side effect profile than statins. In this double-blinded randomized trial, adult patients with increased cardiovascular risk and reporting unwillingness to receive statins due to their adverse effects were randomized to receive daily bempedoic acid or placebo. Patients were followed for a median duration of 40.6 months. Reduction in mean LDL was greater in the bempedoic acid group. The primary outcome event, defined by a composite incidence of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, occurred significantly more in the placebo group. Fatal or nonfatal myocardial infarction and coronary revascularization both independently occurred more in the placebo group. Incidences of overall adverse events, serious adverse events, or adverse events leading to discontinuation did not differ between groups. A limitation of the study was that the patient population had a high mean LDL cholesterol level at baseline. Therefore, the study was not able to study the effects of bempedoic acid in patients with lower LDL cholesterol. In addition, treatment efficacy and safety were not directly compared to statin.
Click to read the study in NEJM
Relevant Reading: Safety and efficacy of bempedoic acid to reduce LDL cholesterol.
In-Depth [randomized controlled trial]: In this double-blinded randomized trial, the efficacy and safety of bempedoic acid were compared to a placebo in adult patients with increased cardiovascular risk. Patients were randomized to receive either daily 180 mg of bempedoic acid (n = 6,992) or placebo (n = 6,078). Patients were followed for a median duration of 40.6 months. Mean LDL cholesterol after six months of treatment with bempedoic acid and placebo was 2.77 mmol per liter and 3.52 mmol per liter, respectively (difference of 21.1 percentage points; 95% Confidence Interval [CI], 20.3 to 21.9)). A primary end-point event (composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) occurred in 11.7% and 13.3% of the bempedoic acid and placebo groups, respectively (hazard ratio, 0.87; 95% CI, 0.79 to 0.96; p=0.0004). For secondary endpoints, a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction occurred in a smaller proportion of the bempedoic acid group compared to the placebo group (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; p=0.006). Fatal or nonfatal myocardial infarction alone and coronary revascularization alone also occurred in a fewer proportion of the bempedoic acid group compared to the placebo group. The overall incidences of adverse events, serious adverse events, and adverse events leading to trial discontinuation did not differ significantly between groups. Bempedoic acid treatment significantly lowered the risk of major adverse cardiovascular events.
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