(187) Real-World Safety and Effectiveness of Evolocumab in Primary Hypercholesterolemia and Mixed Dyslipidemia in Saudi Arabia

Background: Hypercholesterolemia and hyperlipidemia are major risks for cardiovascular diseases. Evolocumab, an orphan drug approved by the FDA for homozygous familial hypercholesterolemia, is a humanized monoclonal antibody that lowers low-density lipoprotein (LDL) levels by 60%. Its short-term efficacy and safety were proven in phase-3 clinical trial, but its long-term safety and effectiveness in the Saudi population are yet to be studied.

Objectives: The aim of this study was to assess the long-term safety and effectiveness of evolocumab in Saudi patients with primary hypercholesterolemia or mixed dyslipidemia.

Methods: A retrospective observational cohort study enrolled adult patients who had recently been prescribed evolocumab for hypercholesterolemia or mixed dyslipidemia. Safety events included myocardial infarction, unstable angina, stroke, transient ischemic attack, heart failure, rhabdomyolysis, renal dysfunction, and myalgia. Effective outcomes included changes in lipid profiles from baseline, assessed at 6-, 12-, 18-, and 24-month. Safety outcomes were estimated using person-years (per 1000 person-years) and effectiveness was estimated using the mean-difference (pre-post) with 95%Confidence interval.

Results: The study involved 469 new evolocumab users, with 69.1% being male. High prevalence of comorbidities included coronary artery disease, diabetes, hypertension, and familial hypercholesterolemia was observed. Statin was the most commonly used therapy. The study's findings, based on four follow-up periods, revealed that the incidence rate of the most frequent adverse events declined as the follow-up period rose. The most common adverse events at 6-month follow-up, based on the incidence rate per 1000 person-years, were coronary revascularization (63.20), myalgia (44.96), myocardial infarction (31.53), unstable angina (31.49), heart failure (26.94), rhabdomyolysis without renal dysfunction (8.93), transient ischemic attack (4.46), and rhabdomyolysis with renal dysfunction (4.46). Stroke incidence increased with follow-up length, from 8.87 per 1000 person-years at 6 months to 12.84 per 1000 person-years at 24 months. Evolocumab use significantly reduced LDL and total cholesterol levels at 6, 12, 18, and 24 months follow-up, while having no significant effect on HDL or triglycerides levels.

Conclusions: Evolocumab is a safe and effective therapeutic option for patients with primary hypercholesterolemia or mixed dyslipidemia to potentially reduce LDL levels to therapeutic levels when statins are insufficient.