Supervisors info:
Ιακωβίδου Νικολέττα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Ξάνθος Θεόδωρος, Καθηγητής, Ιατρική Σχολή, Ευρωπαϊκό Πανεπιστήμιο Κύπρου
Χαλκιάς Αθανάσιος, Επίκουρος Καθηγητής, Ιατρική Σχολή, Πανεπιστήμιο Θεσσαλίας
Summary:
Introduction: Proprotein Convertase Subtilisin – kexin 9 (PCSK9) inhibitors (PCSK9i) are powerful means to lower blood lipid levels, which have already proved that they improve the clinical outcomes in hypercholesterolemic patients. Nevertheless, it is still not completely clear how effective they are in patients of medium, high, and very high cardiovascular risk having diabetes mellitus type II. In addition, it is unclear if the drug substances (alirocumab and evolocumab) and the different dosages have different efficacies. For this reason, recently published trials were used in this meta-analysis in order to systematically assess the efficacy and safety of PCSK9i, examining the lipid profile, the adverse outcomes and the clinical endpoints in patients of medium, high and very high cardiovascular risk having diabetes mellitus type II.
Methodology: Randomized Controlled Trials (RCTs) that compared the PCSK9i with placebo in diabetics of medium, high and very high cardiovascular risk were retrieved from electronic databases by two independent investigators with publication dates from January 2013 until June 2020. In the efficacy and safety results low-density-lipoprotein cholesterol (LDL-C), other lipid profiles and therapy-related adverse outcomes are included. Furthermore, subgroup analyses on the drug substances and dosages were performed.
Results: Four RCTs fulfilling all the inclusion criteria and none of the exclusion criteria were included in the meta-analysis. PCSK9i significantly improved LDL-C levels and the rest lipid profile (P<0.05). The dosages of 75mg alirocumab biweekly, 300mg alirocumab monthly and 420mg evolocumab monthly result in statistically significant greater decrease in LDL-C levels, compared with control group (median = -57.88%, 95% (CI)= [-66.90%, -48.86%]). In general, monoclonal antibodies PCSK9i were safe, without statistically significant difference between the groups concerning the adverse outcomes (RR= 0.02, 95% CI= [-0.01, 0.04]).
Conclusion: Alirocumab and evolocumab are both tolerated well and can significantly improve the lipid profile of patients of medium, high, and very high cardiovascular risk having diabetes mellitus type II.
