Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: a systematic review and meta-analysis Academic Article uri icon

abstract

  • 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.

authors

  • Cicero, AFG
  • Fogacci, F
  • Hernandez, AV
  • Banach, M
  • Alnouri, F
  • Amar, F
  • Atanasov, AG
  • Bajraktari, G
  • Bartlomiejczyk, MA
  • Bjelakovic, B
  • Bruckert, E
  • Bielecka-Dabrowa, A
  • Cafferata, A
  • Ceska, R
  • Collet, X
  • Descamps, O
  • Devaki, N
  • Djuric, D
  • Durst, R
  • Ezhov, MV
  • Fras, Z
  • Gaita, D
  • von Haehling, S
  • Jones, SR
  • Jozwiak, J
  • Kakauridze, N
  • Katsiki, N
  • Khera, A
  • Kostner, K
  • Kubilius, R
  • Latkovskis, G
  • Mancini, GBJ
  • Marais, AD
  • Martin, SS
  • Martinez, JA
  • Mazidi, M
  • Mikhailidis, DP
  • Mirrakhimov, E
  • Miserez, AR
  • Mitchenko, O
  • Moriarty, P
  • Nabavi, SM
  • Panagiotakos, Demosthenes
  • Paragh, G
  • Pella, D
  • Penson, PE
  • Petrulioniene, Z
  • Pirro, M
  • Postadzhiyan, A
  • Puri, R
  • Reda, A
  • Reiner
  • Riadh, J
  • Richter, D
  • Rizzo, M
  • Ruscica, M
  • Sahebkar, A
  • Sattar, N
  • Serban, MC
  • Shehab, AMA
  • Shek, AB
  • Sirtori, CR
  • Stefanutti, C
  • Tomasik, T
  • Toth, PP
  • Viigimaa, M
  • Vinereanu, D
  • Vohnout, B
  • Vrablik, M
  • Wong, ND
  • Yeh, HI
  • Zhisheng, J
  • Zirlik, A

publication date

  • 2020