Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: A systematic review and meta-analysis

Heyue Du, Xiaodan Li, Na Su, Ling Li, Xiaoting Hao, Haihui Gao, Joey S. W. Kwong, Per Olav Vandvik, Xueli Yang, Imola Nemeth, Ify Mordi, Qianrui Li, Longhao Zhang, Li Rao, Chim Lang, Jianshu Li, Haoming Tian, Sheyu Li (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
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Background: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE).

Methods: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence.

Results: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence.

Conclusions: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke.

Trial registration: PROSPERO; CRD42017073904.

Original languageEnglish
Pages (from-to)1149-1159
Number of pages11
Issue number15
Early online date6 Mar 2019
Publication statusPublished - Aug 2019


  • cardiovascular disease
  • lipid-lowering drugs
  • low-density lipoprotein cholesterol
  • proprotein convertase subtilisin/kexin type 9 inhibitors
  • systematic review

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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