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: We conducted a systematic review of literature according to the PRISMA statement. A total of 8 randomized control trials (RCTs) enrolling 20 651 patients with diabetes were included. Mean follow-up was 51 weeks. We included RCTs which had compared the PCSK9i alirocumab and evolocumab with placebo in subjects with hypercholesterolemia and diabetes mellitus. Results: 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% (relative risk [RR] 0.82, 95% confidence interval [CI] 0.74-0.90). Compared to control group, the use of PCSK9 inhibitors was associated with a significant % change from baseline in LDL-C (mean difference [MD]-58.48%; 95% CI: -63.73 to -53.22%), P < 0.0001), HDL-C (MD5.21%; 95% CI: 3.26 to 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 Lp(a) (MD-32.90%; 95% CI: -38.55 to -27.24%)and ApoB (MD-46.83%; 95% CI: -52.71 to -40.94%)were observed in PCSK9i group compared to placebo. Conclusions: PCSK9i appear to be effective in reducing the risk of MACE and in improving lipid profiles of subjects with diabetes and dyslipidemia.