Bempedoic Acid Reduces Nonfatal Myocardial Infarction in Patients With Hyperlipidemia

Among patients with hyperlipidemia, bempedoic acid can decrease risk for nonfatal myocardial infarction.

Bempedoic acid is associated with a decrease in nonfatal myocardial infarction (MI) among patients with hyperlipidemia, but it has no significant effect on stroke and all-cause mortality, researchers reported in the European Heart Journal–Cardiovascular Pharmacotherapy.

The findings are based on a systematic review and meta-analysis of randomized clinical trials of bempedoic acid. A systematic search was conducted in the PubMed, Web of Science, and Embase databases through March 20, 2023. Eligible trials were published in English and compared bempedoic acid at an initial dose of 180 mg daily with placebo in patients who had an indication for low-density lipoprotein cholesterol (LDL-C)-lowering therapy.

The primary endpoint was 3-point major adverse cardiovascular events (MACE) that included cardiovascular death, nonfatal MI, or nonfatal stroke. The analysis included 10 manuscripts with 18,200 patients (9765 receiving bempedoic acid and 8435 receiving placebo).

For the analysis of MACE, 5 studies were included. A significant difference was observed between bempedoic acid (n=669) and placebo (n=720; odds ratio [OR], 0.84; 95% CI, 0.76-0.96; P <.001). No significant amount of heterogeneity was found (Chi2 =3.90, P =.42, Tau2 =0.00, I2 =0%).

As bempedoic acid did not reduce mortality, it should primarily be prescribed in patients with a true contraindication to statins or those who do not reach treatment goals on otherwise optimal lipid-modifying therapy.

All-cause death analysis included 3 studies. No significant difference was observed between bempedoic acid (n=453) and placebo (n=424; OR, 1.19; 95% CI, 0.73-1.93; P =.49), and no significant amount of heterogeneity occurred in the true outcomes (Chi2 =2.45, P =.29, Tau2 =0.07; I2 =18%).

For myocardial infarction, 5 studies were included in the analysis. A significant difference was observed between bempedoic acid (n=290) and placebo (n=359; OR, 0.75; 95% CI, 0.64-0.88; P <.001). No significant amount of heterogeneity was observed (Chi2 =2.82, P =.59, Tau2 =0.00, I2 =0%). In meta-regression analysis, the mean LDL change was not a significant predictor for future outcomes (P >.05).

The analysis of stroke included 4 studies, and no significant difference was found between bempedoic acid (n=146) and placebo (n=162; OR, 0.86; 95% CI, 0.69-1.08; P =.20). No significant amount of heterogeneity was observed in the outcomes (Chi2=0.67, P =.88, Tau2 =0.00, I2 =0%).

Bempedoic acid was associated with an 11% increased relative rate of treatment discontinuation vs controls (OR, 1.11; 95% CI, 1.01-1.23; P =.03; I2 =0%). Bempedoic acid had a significant association with increased rates of elevated liver enzymes, hyperuricemia, renal impairment, and gout (all P <.05).

Among several limitations, the analysis included results from trials that had variations in treatment duration, enrollment criteria, and lipid-modifying background therapy. In addition, the effect of bempedoic acid at the patient level was not evaluated.

“As bempedoic acid did not reduce mortality, it should primarily be prescribed in patients with a true contraindication to statins or those who do not reach treatment goals on otherwise optimal lipid-modifying therapy,” the study authors wrote.

References:

Mutschlechner D, Tscharre M, Huber K, Gremmel T. Cardiovascular events in patients treated with bempedoic acid versus placebo: systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. Published online July 18, 2023. doi: 10.1093/ehjcvp/pvad052