Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia: A meta-analysis of 35 randomized controlled trials

Aris Karatasakis, Barbara A. Danek, Judit Karacsonyi, Bavana V. Rangan, Michele K. Roesle, Thomas Knickelbine, Michael D. Miedema, Houman Khalili, Zahid Ahmad, Shuaib Abdullah, Subhash Banerjee, Emmanouil S. Brilakis

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112 Scopus citations


Background--We sought to examine the efficacy and safety of 2 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab. Methods and Results--We performed a systematic review and meta-analysis of randomized controlled trials comparing treatment with and without PCSK9 inhibitors; 35 randomized controlled trials comprising 45 539 patients (mean follow-up: 85.5 weeks) were included. Mean age was 61.0±2.8 years, and mean baseline low-density lipoprotein cholesterol was 106±22 mg/dL. Compared with no PCSK9 inhibitor therapy, treatment with a PCSK9 inhibitor was associated with a lower rate of myocardial infarction (2.3% versus 3.6%; odds ratio [OR]: 0.72 [95% confidence interval (CI), 0.64-0.81]; P < 0.001), stroke (1.0% versus 1.4%; OR: 0.80 [95% CI, 0.67-0.96]; P=0.02), and coronary revascularization (4.2% versus 5.8%; OR: 0.78 [95% CI, 0.71-0.86]; P < 0.001). Overall, no significant change was observed in all-cause mortality (OR: 0.71 [95% CI, 0.47- 1.09]; P=0.12) or cardiovascular mortality (OR: 1.01 [95% CI, 0.85-1.19]; P=0.95). A significant association was observed between higher baseline low-density lipoprotein cholesterol and benefit in all-cause mortality (P=0.038). No significant change was observed in neurocognitive adverse events (OR: 1.12 [95% CI, 0.88-1.42]; P=0.37), myalgia (OR: 0.95 [95% CI, 0.75-1.20]; P=0.65), new onset or worsening of preexisting diabetes mellitus (OR: 1.05 [95% CI, 0.95-1.17]; P=0.32), and increase in levels of creatine kinase (OR: 0.84 [95% CI, 0.70-1.01]; P=0.06) or alanine or aspartate aminotransferase (OR: 0.96 [95% CI, 0.82- 1.12]; P=0.61). Conclusions--Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes. Although no overall benefit was noted in all-cause or cardiovascular mortality, such benefit may be achievable in patients with higher baseline lowdensity lipoprotein cholesterol.

Original languageEnglish (US)
Article numbere006910
JournalJournal of the American Heart Association
Issue number12
StatePublished - Dec 1 2017


  • Alirocumab
  • Evolocumab
  • Hyperlipidemia
  • Outcome
  • PCSK9

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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