Article Impact Level: HIGH Data Quality: STRONG Summary of Mayo Clinic Proceedings, S0025619625000758. https://doi.org/10.1016/j.mayocp.2025.01.018 Dr. Maciej Banach et al.
Points
- Combination lipid-lowering therapy (LLT) significantly outperformed statin monotherapy in lowering LDL-C levels among very high-risk patients, with a mean reduction difference of nearly 13 mg/dL across pooled studies.
- Clinical outcomes favored combination LLT, showing notable reductions in all-cause mortality, major adverse cardiovascular events, and stroke incidence compared to statin-only treatments, with statistically significant odds ratios reported.
- No significant difference was observed in cardiovascular mortality between the two groups, suggesting combination LLT’s benefits do not extend to this specific outcome in the reviewed population.
- Both treatment strategies had similar rates of adverse events and discontinuation, indicating that combination LLT offers greater effectiveness without compromising patient safety or tolerability.
- Researchers recommend considering early use of combination LLT for high- and very high-risk patients to achieve LDL-C targets and enhance cardiovascular outcomes, urging updates to clinical guidelines.
Summary
In this systematic review, the efficacy of combination lipid-lowering therapy (LLT) was compared to statin monotherapy in reducing low-density lipoprotein cholesterol (LDL-C) levels and improving cardiovascular outcomes in high-risk patients. 14 studies, including 11 randomized controlled trials and 3 cohort studies, were included, with 108,373 participants aged 67.31 years (combination therapy) and 67.89 years (statin monotherapy). Pooled results indicated that combination LLT was more effective than statin monotherapy in reducing LDL-C levels by a mean difference of −12.96 mg/dL (95% CI, −17.27 to −8.65; P<.001).
Combination LLT was also associated with significant improvements in clinical outcomes, including a reduction in all-cause mortality (odds ratio [OR], 0.81; 95% CI, 0.67 to 0.97; P=.02), major adverse cardiovascular events (MACE) (OR, 0.82; 95% CI, 0.69 to 0.97; P=.02), and stroke incidence (OR, 0.83; 95% CI, 0.75 to 0.91; P<.001), compared to statin monotherapy. However, no significant difference was observed in cardiovascular mortality (OR, 0.86; 95% CI, 0.65 to 1.12; P=.26). Importantly, the rates of adverse events and therapy discontinuation were similar between the two groups, suggesting no increased risk from combination therapy.
The findings of this study suggest that combination LLT is a more effective treatment for reducing LDL-C levels and improving cardiovascular outcomes, with no additional adverse effects compared to statin monotherapy. Given these benefits, the authors recommend that combination LLT be considered early in treatment for high- and very high-risk patients, particularly to achieve LDL-C goals and reduce cardiovascular morbidity and mortality. Future guidelines should reflect this strategy for more optimal patient care.
Link to the article: https://www.mayoclinicproceedings.org/article/S0025-6196(25)00075-8/fulltext
References Banach, M., Jaiswal, V., Ang, S. P., Sawhney, A., Deb, N., Amarenco, P., Gaita, D., Reiner, Z., Pećin, I., Lavie, C. J., Penson, P. E., & Toth, P. P. (2025). Impact of lipid-lowering combination therapy with statins and ezetimibe vs statin monotherapy on the reduction of cardiovascular outcomes: A meta-analysis. Mayo Clinic Proceedings, S0025619625000758. https://doi.org/10.1016/j.mayocp.2025.01.018
