Article Impact Level: HIGH Data Quality: STRONG Summary of New England Journal of Medicine, 388(15), 1353–1364. https://doi.org/10.1056/NEJMoa2215024 Dr. Steven Nissen et al.
Points
- Bempedoic acid, an ATP citrate lyase inhibitor, was studied in a double-blind, randomized, placebo-controlled trial in statin-intolerant patients at high risk for cardiovascular disease.
- Treatment with bempedoic acid resulted in a significant reduction in LDL cholesterol levels compared to placebo.
- Bempedoic acid demonstrated a lower incidence of major adverse cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.
- The composite cardiovascular events, fatal or nonfatal myocardial infarction, and coronary revascularization were significantly lower with bempedoic acid.
- Bempedoic acid did not significantly affect fatal or nonfatal stroke, death from cardiovascular causes, or death from any cause. However, it was associated with higher incidences of gout, cholelithiasis, and small increases in specific blood markers.
Summary
This double-blind, randomized, placebo-controlled trial investigated the cardiovascular outcomes of bempedoic acid, an ATP citrate lyase inhibitor, in patients who were unable or unwilling to take statins due to unacceptable adverse effects. A total of 13,970 patients, referred to as “statin-intolerant” patients, were randomly assigned to receive either oral bempedoic acid, 180 mg daily, or a placebo. The primary endpoint was a four-component composite of major adverse cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.
During a median follow-up of 40.6 months, the baseline mean LDL cholesterol level was 139.0 mg per deciliter in both groups. After six months, the reduction in LDL cholesterol was significantly greater with bempedoic acid compared to placebo, with a difference of 29.2 mg per deciliter. Furthermore, the percent reductions in LDL cholesterol were 21.1 percentage points higher in favor of the bempedoic acid group. The incidence of the primary endpoint event was significantly lower with bempedoic acid compared to placebo, with 11.7% of patients in the treatment group experiencing the event, compared to 13.3% in the placebo group. The hazard ratio was 0.87, with a 95% confidence interval of 0.79 to 0.96 (P=0.004).
In addition, bempedoic acid demonstrated lower incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (8.2% vs. 9.5%; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.006), fatal or nonfatal myocardial infarction (3.7% vs. 4.8%; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P=0.002), and coronary revascularization (6.2% vs. 7.6%; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P=0.001). However, bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, or death from any cause.
While the use of bempedoic acid reduced the risk of major adverse cardiovascular events in statin-intolerant patients, it was associated with higher incidences of gout (3.1% vs. 2.1%) and cholelithiasis (2.2% vs. 1.2%) compared to the placebo group. Furthermore, there were slight increases in serum creatinine, uric acid, and hepatic-enzyme levels in the bempedoic acid group.
In conclusion, treatment with oral bempedoic acid was associated with a lower risk of major adverse cardiovascular events in statin-intolerant patients. This research provides evidence for bempedoic acid as a potential alternative treatment option for patients unable to tolerate statins.
Link to the article: https://www.nejm.org/doi/full/10.1056/NEJMoa2215024
References Nissen, S. E., Lincoff, A. M., Brennan, D., Ray, K. K., Mason, D., Kastelein, J. J. P., Thompson, P. D., Libby, P., Cho, L., Plutzky, J., Bays, H. E., Moriarty, P. M., Menon, V., Grobbee, D. E., Louie, M. J., Chen, C.-F., Li, N., Bloedon, L., Robinson, P., … Nicholls, S. J. (2023). Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. New England Journal of Medicine, 388(15), 1353–1364. https://doi.org/10.1056/NEJMoa2215024
