Ezetimibe plus statin combination versus double-dose statin in patients with dyslipidemia and atherosclerotic cardiovascular disease risk: a comprehensive systematic review and meta-analysis of 47 randomized controlled trials.

Background: Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Oral regimens to achieve blood lipid targets include increasing the statin dose or adding ezetimibe to statin therapy. The optimal strategy remains debated. This study evaluated the efficacy and safety of ezetimibe plus statin versus a double dose of the same statin in patients with ASCVD risk.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from PubMed, Embase, Cochrane, Scopus, and Web of Science through December 2023. A random-effects model was used to analyze outcomes, reporting risk ratio and mean difference with 95% confidence intervals.

Results: Forty-seven randomized controlled trials involving 18,592 patients were included. Ezetimibe plus statin significantly reduced low-density lipoprotein (LDL) cholesterol (P < 0.001), triglyceride (P = 0.019), and total cholesterol levels (P < 0.001) and increased target LDL achievement (P < 0.0001) compared to double-dose statin. No significant differences were observed in high-density lipoprotein levels, any adverse events, all-cause mortality, myocardial infarction, angina, or nonfatal stroke. The incidence of severe adverse events was higher with ezetimibe plus statin (P = 0.03).

Conclusion: Ezetimibe plus statin therapy demonstrated superior lipid-lowering efficacy compared with double-dose statin therapy, with no additional clinical benefit. There was no difference in overall adverse events. There was a higher incidence of severe adverse events with combination therapy compared to double-dose statin therapy, although these events were rare and not believed to be attributable to medication.