Efficacy and outcomes of Bempedoic acid versus placebo in patients with statin-intolerance: A pilot systematic review and meta-analysis of randomized controlled trials.

ABSTRACT

INTRODUCTION: Bempedoic acid (BA) has shown significant progress in reducing cholesterol levels and is relatively free from the many side effects encountered with the use of other hyperlipidemic drugs such as statins. However, its efficacy in patients with statin intolerance is controversial with inconsistent results among studies. MATERIALS AND METHODS: An electronic literature search was performed using various databases such as Medline, Google Scholar, and the International Registry of Clinical Trials. The primary endpoint was the change in LDL-C levels. The secondary endpoints included changes in HDL-C, non-HDL-C, triglycerides (TG), clinical outcomes such as MACE, all-cause mortality (ACM), cardiovascular mortality, myocardial infarction (MI), and additional safety outcomes. The least-square mean (LSM) percent change for assessing changes in lipid parameter levels from the baseline and the risk ratio (RR) were used for the evaluation of binary endpoints, with statistical significance set at p<0.05. Random-effects meta-analyses were performed for all the outcomes. RESULTS: Our analysis included 5 randomized controlled trials (RCTs) with a total of 18,848 participants. BA showed a significant reduction in LDL-C [LSM difference in % -25.24; 95 % CI -30.79 to -19.69; p < 0.00001], total cholesterol [LSM difference in %-21.28; 95 % CI-30.58 to-11.98; p < 0.00001], non-HDL-C [LSM difference in % -23.27; 95 % Cl -29.80 to -16.73 p < 0.00001], and HDL-C [LSM difference in %-3.37, 95 % CI-3.73 to-3.01, p < 0.00001] compared to placebo. In terms of clinical efficacy, BA was associated with a lower risk of coronary revascularization [RR0.81; 95 % CI0.66 to 0.99; p = 0.04], hospitalization for unstable angina [RR0.67; 95 % CI0.50 to 0.88; p = 0.005], and myocardial infarction [RR0.76; 95 % CI0.66 to 0.88;p = 0.0004]. No significant difference was observed in MACE [RR0.81; p = 0.15], ACM [RR0.86; p = 0.46], cardiovascular-related mortality [RR0.79; p = 0.44], and stroke [RR0.83; p = 0.08] between the two groups. In terms of safety efficacy, the risk for myalgia was significantly lower in BA-treated patients than in placebo [RR0.80; p = 0.0002], while the risk for gout [RR1.46; p < 0.0001] and hyperuricemia [RR1.93; p < 0.00001] was higher for BA than for placebo. The risks for other adverse effects, such as neurocognitive disorder, nasopharyngitis urinary tract infection, upper respiratory infection, muscular disorder, and worsening hyperglycemia/DM were comparable between the two groups. CONCLUSION: Our analysis demonstrated that BA significantly reduced the levels of LDL-C, total cholesterol, non-HDL-C, HDL-C, ApoB, and hs-CRP compared with the placebo group. Additionally, patients who received BA had a lower likelihood of coronary revascularization and hospitalization due to unstable angina, MI, and myalgia. Further large-scale RCTs are required to generate more robust evidence.