The efficacy of PCSK9 inhibitors on major cardiovascular events and lipid profile in patients with diabetes: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Objective To evaluate the specific effects of PCSK9 inhibitors (i.e. alirocumab and evolocumab) on major cardiovascular events (MACE) and lipid profile in patients with diabetes. Methods and results We conducted a systematic review of literature according to the PRISMA statement. A total of eight randomized control trials (RCTs) enrolling 20 651 patients with diabetes were included. The mean follow-up was 51 weeks. We included RCTs that had compared the subtilisin–kexin type 9 inhibitors (PCSK9i) alirocumab and evolocumab with placebo in subjects with hypercholesterolaemia and diabetes mellitus. MACE occurred in 8.7% of patients with diabetes randomized to PCSK9i vs. 11.0% of those randomized to placebo. Thus, the use of alirocumab or evolocumab reduced MACE by 18% [odds ratio (OR): 0.82; 95% confidence interval (CI): 0.74–0.90]. Compared with control group, the use of PCSK9 inhibitors was associated with a significant percentage change from baseline in low-density lipoprotein cholesterol [mean difference (MD) –58.48%; 95% CI: –63.73 to –53.22%, P < 0.0001], high-density lipoprotein cholesterol (HDL-C) (MD 5.21%; 95% CI: 3.26–7.17%), triglycerides (MD –14.59%; 95% CI: –19.42 to –9.76%), non-HDL-C (MD –48.84%; 95% CI: –54.54 to –43.14%), and total cholesterol (MD –33.76%; 95% CI: –38.71 to –28.8%). Moreover, a significant reduction of lipoprotein(a) (MD –32.90%; 95% CI: –38.55 to –27.24%) and apolipoprotein B (MD –46.83%; 95% CI: –52.71 to ––40.94%) were observed in PCSK9i group compared with placebo. Conclusion PCSK9i appear to be effective in reducing the risk of MACE and in improving lipid profiles of subjects with diabetes and dyslipidaemia.