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.
- cardiovascular disease
- low-density lipoprotein cholesterol
- lipid-lowering drugs
- proprotein convertase subtilisin/kexin type 9 inhibitors
- systematic review
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HD, XL and NS were the co-first authors.
HD, XL and NS contributed equally.
Contributors HT, JL and SL: planned this study. HD, XL, NS, XH and HG: performed the literature search and screening. HD, XL and NS: extracted the study data. HD and NS: performed the risk of bias assessment. HD, LL and LZ: performed the statistical analyses. JS-WK, POV and XY: provided critical comments in methodology and revised the manuscript. MRI, LR and CCL: provided critical comments in clinical cardiology. HD, XL, IN, MRI and SL: drafted the manuscript. All authors critically reviewed the manuscript and participated in the interpretation of the results. SL: is responsible for the overall content as the guarantor.
Funding This study was supported by grants from the National Natural Science Foundation of China (grant number 81400811 and 21534008), Cholesterol Fund by China Cardiovascular Foundation and China Heart House and the International Visiting Program for Excellent Young Scholars of Sichuan University.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
Correction notice Since this article was first published online, the author name Ify R Mordi has been corrected.