Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis


Autoři: Arrigo F. G. Cicero aff001;  Federica Fogacci aff001;  Adrian V. Hernandez aff002;  Maciej Banach aff004
Působiště autorů: Hypertension and Cardiovascular Risk Factors Research Group, Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy aff001;  Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, Connecticut, United States of America aff002;  Vicerrectorado de Investigacion, Universidad San Ignacio de Loyola, Lima, Peru aff003;  Chair of Nephrology and Hypertension, Department of Hypertension, Medical University of Lodz, Lodz, Poland aff004;  Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland aff005;  Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland aff006
Vyšlo v časopise: Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis. PLoS Med 17(7): e32767. doi:10.1371/journal.pmed.1003121
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003121

Souhrn

Background

Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile.

Methods and findings

We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel–Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD −14.94%; 95% CI −17.31%, −12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD −18.17%; 95% CI −21.14%, −15.19%; p < 0.001), low-density lipoprotein cholesterol (MD −22.94%; 95% CI −26.63%, −19.25%; p < 0.001), low-density lipoprotein particle number (MD −20.67%; 95% CI −23.84%, −17.48%; p < 0.001), apolipoprotein B (MD −15.18%; 95% CI −17.41%, −12.95%; p < 0.001), high-density lipoprotein cholesterol (MD −5.83%; 95% CI −6.14%, −5.52%; p < 0.001), high-density lipoprotein particle number (MD −3.21%; 95% CI −6.40%, −0.02%; p = 0.049), and hsCRP (MD −27.03%; 95% CI −31.42%, −22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD −1.51%; 95% CI −3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI −9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD −1.83%; 95% CI −5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length.

Conclusions

Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.

Klíčová slova:

Database searching – Cholesterol – Lipids – Lipoproteins – Metaanalysis – Plasma proteins – Publication ethics – Statins


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