Objective: To evaluate the specific effects of 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 20651 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), without differences between PCSK9i compounds (p= 0.70, I2 0.0%). 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%). A significant reduction of Lp(a) (MD-32.90%; 95% CI: -38.55 to -27.24%) were observed in PCSK9i group compared to placebo. Moreover, while LDL-C reduction was similar in both subgroups (Evolocumab: MD -63,3%; 95% CI: -74.87 to -51.72%, p<0.0001; alirocumab: MD -55.58%; 95% CI: -61.49 to -49.67%, p<0.0001; Test for subgroup differences: P= 0.24; I226.2%), the percentage of Lp(a) reduction was higher in evolocumab subgroup compared to alirocumab (MD -46.68 %; 95% CI: -60.73 to -32.63%, p<0.0001 vs -22.92 %; 95% CI: -28.58 to -17.25%, p<0.0001, respectively; Test for subgroup differences: P= 0.002; I2=89.4%).
Conclusions: Alirocumab and evolocumab appear to be effective in reducing the risk of MACE in subject with diabetes. Moreover, the use of PCSK9 inhibitors provides enhancement of lipid profile of patients with diabetes and dyslipidemia by reducing LDL-c and Lp(a) values.