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.

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.