Statin Plus Ezetimibe Outperforms High-Dose Statins in LDL-C Reduction: Daily Dose

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On August 23, 2024, we reported on a study published in the journal Clinical Cardiology that compared the efficacy and safety of high-intensity statins vs low/moderate-intensity statins plus ezetimibe for LDL-C reduction in patients with atherosclerotic cardiovascular disease (ASCVD).

The study

Researchers searched PubMed, Embase, and Web of Science databases for relevant studies from inception to July 2023 to compare the 2 lipid-lowering strategies. They included all randomized controlled trials (RCTs) comparing high-intensity statin monotherapy with low/moderate-intensity statin plus ezetimibe combination therapy in patients with ASCVD.

From the initial total of 3060 articles, 32 remained for the analysis after applying eligibility criteria. The full cohort comprised 6162 persons treated with high-intensity statin monotherapy and 5880 treated with combination ezetimibe and statin therapy. Treatment duration across the studies ranged from 1 to 36 months.

The findings

Overall, 21 of these studies compared the effect of high-intensity statin monotherapy versus combination therapy on LDL-C levels in patients with ASCVD. The mean difference (MD) in LDL-C lowering between combined therapy and monotherapy was –6.6 (95% CI, –10.6 to –2.5). Investigators reported no significant differences, however, in effects on other surrogate markers including high-density lipoprotein cholesterol, triglycerides, total cholesterol, or high-sensitivity C-reactive protein between the 2 treatment approaches.

Results also showed that the combination therapy group experienced a lower risk of myalgia (RR 0.27, 95% CI 0.13–0.57) and discontinuation due to adverse events (RR 0.61, 95% CI 0.51–0.74). The occurrence of major adverse cardiovascular events (MACE) was similar between the 2 treatment groups.

Authors' comment

“Although our study did not demonstrate a clear superiority of combination therapy in reducing MACE, the significant reduction in LDL-C levels and improved tolerability profiles observed with this approach may still provide important clinical benefits."

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