European Journal of Biomedical and Pharmaceutical Sciences

EFFICACY AND SIDE EFFECT PROFILE OF PCSK9 INHIBITORS: WHAT DO META-ANALYSES SAY? A REVIEW

Paudel K. R.*, Panta R.

ABSTRACT

Introduction: Hypercholesterolemia is associated with increased risk of heart disease and stroke. Heart disease is the first leading cause of death and the stroke is the fifth leading cause of death. In the world, 33% of ischemic heart disease is due to hypercholesterolemia (total blood cholesterol ≥ 200 mg/dL) which causes approximately 4.5% of the total death globally and 2% of total disability-adjusted life year, and its global prevalence is about 39%. In the US, 2 in 5 (40%) adults (≥20 years) and almost 7% of children and adolescents (6 to 19 years) have hypercholesterolemia. Methods: We conducted a literature search and a review of meta-analyses in Pubmed, Chochrane library and Google published up to November 4, 2022. The key words used for literature search were hypercholesterolemia, PCSK9 inhibitors and hyperlipidemia. Meta-analyses consisting effects of PCSK9 inhibitors on lipid profile, cardiovascular events and side effect profile were included in the study. Results: PCSK9 inhibitors significantly reduced LDL-C, TC, TG, LP(a) and increased HDL-C. PCSK9 inhibitors reduced the all-cause death and cardiovascular events. However, these effects were not statistically significant. Additionally, these drugs were associated with lower risk of MI, stroke and cardiac revascularization (P<0.05). PCSK9 inhibitors may increase blood sugar level and HbA1c. Nevertheless, these drugs are not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97). Conclusion: PCSK9 inhibitors in combination therapy reduced the LDL-C, TC, TG, LP (a) levels and increased HDL-C and their use was associated with a statistically significant reduction in MI, stroke, and coronary revascularization. PCSK9 inhibitors were not significantly associated with neurocognitive adverse events, incident or worsening of preexisting diabetes mellitus, creatine kinase increase, myalgia, and increase in alanine or aspartate aminotransferase.

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