The Clinical Efficacy and Safety of Bempedoic Acid in Patients at Elevated Risk of Cardiovascular Disease: A Meta-Analysis of Randomized Clinical Trials

Abstract

Purpose Statins are first-line agents to reduce low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, however, they are insufficient and/or intolerable in many patients. To that end, we conducted a meta-analysis of Bempedoic Acid (BA), a novel LDL-C lowering agent. Methods We retrieved randomized clinical trials (RCTs) of BA by searching Pubmed, the Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov. We used the Mantel-Haenszel method to pool estimates. The I2 measure was used to quantify heterogeneity. Treatment effects are provided as relative risks (RR), absolute risk differences (ARD), and number needed to treat/harm (NNTB/H). Analyses were conducted using R, version 4.1.2. Results 11 trials enrolling 18,496 patients were included. Compared to placebo, BA reduced the risk of major adverse cardiovascular events (RR: 0.87; 95% CI: 0.80 to 0.95; ARD: -1.63%; NNT: 62), myocardial infarction (RR: 0.76; 95% CI: 0.66 to 0.89; ARD: -1.03%; NNT: 98), unstable angina hospitalization (RR: 0.70; 95%: CI: 0.55 to 0.89; ARD: -0.57%; NNT: 177), revascularization (RR: 0.81; 95% CI: 0.72 to 0.91; ARD: -1.31%; NNT: 77), and myalgia (RR: 0.85; 95% CI: 0.75 to 0.95; ARD: -0.99%; NNT: 102). BA significantly increased the risk of gout (RR: 1.56; 95% CI: 1.27 to 1.91; ARD: 0.99%; NNH: 101), renal impairment (RR: 1.35; 95% CI: 1.22 to 1.49; ARD: 2.54%; NNH: 40), and cholelithiasis (RR: 1.87; 95% CI: 1.43 to 2.44; ARD: 1.01%; NNH: 100). Conclusion BA effectively reduces the risk of cardiovascular events and myalgia but increases the risk of gout, cholelithiasis, and renal impairment.

Dyslipidaemia in elderly and stroke patients

“…A pooled analysis of 3660 patients from the ORION trials focused on different age groups and included 39.1 % patients aged ≥65 to <75 years and 13.4 % patients aged ≥75 years. 19 , 20 Moreover, the LDL-C-lowering effect (approximately − 50 %) did not differ across age groups. Also the estimated glomerular filtration rate had to be > 30 ml/min in ORION 9, ORION 10, and ORION 11, because there is no daily dosing with Inclisiran, and the mechanism of action is not directly linked to plasma exposure, no dose adjustment is recommended in renal disease.…”

“… 18 Another recent meta-analysis over 11 RCTs comprising of 18,496 patients has concluded that although bempedoic acid effectively reduces the risk of cardiovascular events and myalgia but it was also found to increase the risk of gout, cholelithiasis, and renal impairment which might be a challenging in elderly populations. 19 Both the authorities EMA and FDA has given a label warning for bempedoic acid regarding the risk of tendon rupture (involving the rotator cuff, biceps tendon, or Achilles tendon) and hyperuricemia/gout especially in patients aged >60 years.…”

Bempedoic Acid: Safety and Efficiacy of a New Lipid-Lowering Agent

“…Проведено несколько метаанализов эффективности и безопасности БК [52][53][54][55][56], в некоторые из них помимо исследований CLEAR были включены другие исследования, менее продолжительные и с меньшим количеством пациентов [57,58]. Результаты этих метаанализов в целом подтверждают вышеуказанные данные.…”

Association between Statins Administration and Influenza Susceptibility: A Systematic Review and Meta-Analysis of Longitudinal Studies

“…Statins, a class of HMG-CoA (hydroxymethylglutaryl CoA) reductase inhibitors, are widely used for the primary and secondary prevention of cardiovascular and cerebrovascular disease [ 1 ], which are ranked first in various causes of death worldwide. It is well known that statins are extensively used as first line agents to reduce the level of low density lipoprotein cholesterol (LDL-C) [ 2 ]. Apart from their role in regulating blood lipids, they have been shown to play roles in anti-thrombotic and anti-inflammatory functions.…”