Meta-analysis on the effect of bempedoic acid in hyperlipidemia
Cardiovascular events in patients treated with bempedoic acid vs. placebo: systematic review and meta-analysisLiterature - Mutschlechner D, Tscharre M, Huber K, et al. - Eur Heart J Cardiovasc Pharmacother. 2023 Sep 20;9(6):583-591. doi: 10.1093/ehjcvp/pvad052
Introduction and methods
For patients who cannot reach guideline-recommended LDL-c goals or those with statin intolerance, bempedoic acid represents a promising novel lipid-modifying agent, either as monotherapy or as part of established lipid-lowering therapies [1,2-17]. Recently, a large RCT showed a lower risk of MACE with bempedoic acid compared with placebo in statin-intolerant patients . However, more data on the safety and CV outcomes of bempedoic acid are needed.
Aim of the study
The authors analyzed the benefits and potential risks of bempedoic acid versus placebo in patients with hyperlipidemia .
In this systematic review and meta-analysis, the authors performed a systematic search in PubMed, Web of Science, and Embase (until March 20, 2023) to identify RCTs comparing bempedoic acid (starting dose: 180 mg daily) with placebo in patients with an indication for LDL-c–lowering therapy. Of the 258 identified publications, 10 fulfilled the inclusion criteria, comprising 18,200 patients in total (9765 on bempedoic acid, 8435 on placebo). Follow-up duration of the included studies ranged from 6 weeks to a median of 40.6 months. All 10 studies were judged to be of overall moderate to high quality.
The primary endpoint was 3-point MACE, consisting of CV death, nonfatal MI, or nonfatal stroke. Secondary endpoints were all-cause mortality, MI, stroke, and adverse events.
- The primary endpoint analysis (5 studies) showed that bempedoic acid reduced the rate of MACE compared with placebo (669/9765 vs. 720/8435 ; OR: 0.84; 95%CI: 0.76–0.96; P<0.001), with no significant amount of heterogeneity (I²=0%).
- Patients treated with bempedoic acid showed a lower incidence of MI compared with placebo-treated patients (290/9765 vs. 359/8435; OR: 0.75; 95%CI: 0.64–0.88; P<0.001; I²=0%).
- However, there were no significant differences between the bempedoic acid and placebo groups in the rates of all-cause mortality (453/9765 vs. 424/8435; OR: 1.19; 95%CI: 0.73–1.93; P=0.49; I²=18%) and stroke (146/9765 vs. 162/8435; OR: 0.86; 95%CI: 0.69–1.08; P=0.20, I²=0%).
- Bempedoic acid treatment was associated with a higher rate of adverse events leading to treatment discontinuation compared with placebo (OR: 1.11; 95%CI: 1.01–1.23; P=0.03; I²=0%) and increased rates of hyperuricemia, gout, elevated liver enzymes, and renal impairment (all P<0.05) but not increases occurrences of creatine kinase, myalgia, or diabetes (all P>0.5).
In this systematic review and meta-analysis, bempedoic acid reduced the incidence of nonfatal MI compared with placebo in patients with hyperlipidemia but had no significant effect on all-cause mortality or stroke. Bempedoic acid treatment was associated with few side effects, including increased rates of hyperuricemia, gout, elevated liver enzymes, and renal impairment. Known side effects of statins, such as increases in creatine kinase, myalgias, and diabetes, were not observed.
Based on their results, the authors believe “[b]empedoic acid is a viable option in patients with true statin intolerance, i.e., rhabdomyolysis or severe hepatopathy, or in the case of LDL-c levels above the treatment goal despite otherwise optimal lipid-modifying therapy. [...] Although ezetimibe and the PCSK-9 inhibitors are currently the preferred agents, in addition to statins, in a clinical routine due to their proven reduction of cardiovascular events, bempedoic acid might be an interesting additional option by replacing other lipid-lowering agents or in combination with those in order to reach the treatment goal early.”