Key result
Adding icosapent ethyl, rivaroxaban, and ezetimibe to aspirin and statins yielded an imputed HR of 0.51 (95% CI 0.42-0.61) for CV death, MI, or stroke in secondary ASCVD prevention.
Why the study?
While icosapent ethyl, rivaroxaban, and ezetimibe individually improve ASCVD outcomes beyond aspirin and statins, the expected aggregate treatment benefit of their combined use is unknown.
Does comprehensive medical therapy (icosapent ethyl, rivaroxaban, and ezetimibe) added to aspirin and statin reduce the composite of cardiovascular death, non-fatal MI, or non-fatal stroke in patients for secondary prevention of ASCVD?
Meta-Analysis (n=53,718)
Does comprehensive medical therapy (icosapent ethyl, rivaroxaban, and ezetimibe) added to aspirin and statin reduce the composite of cardiovascular death, non-fatal MI, or non-fatal stroke in patients for secondary prevention of ASCVD?
The theoretical addition of icosapent ethyl, rivaroxaban, and ezetimibe to standard aspirin and statin therapy may substantially reduce cardiovascular events in secondary prevention of ASCVD.
Supports adding three agents to aspirin/statins in secondary ASCVD prevention; extends single-drug data via imputed combination effects.
PURPOSE: Interest in improving residual cardiovascular (CV) risk by targeting multiple causative pathways has been growing. Several medications including icosapent ethyl, rivaroxaban, and ezetimibe have been shown to individually improve outcomes in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD) beyond conventional therapy consisting of aspirin and statins. While each drug has been shown to individually improve outcomes, the expected treatment benefit of the combined use of these drugs for enhanced secondary prevention of ASCVD is not known. METHODS: In this cross-trial analysis, we estimated the aggregate treatment effect of comprehensive medical therapy consisting of icosapent ethyl, rivaroxaban, and ezetimibe added to background aspirin and statin therapy through established methods of indirect comparisons of the results of three key clinical trials (REDUCE-IT [n = 8,179], COMPASS [n = 27,395], and IMPROVE-IT [n = 18,144]). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary endpoints included each individual component of the primary endpoint. RESULTS: The hazard ratio (HR) of the imputed aggregate treatment effects for enhanced secondary prevention of ASCVD with comprehensive disease modifying therapy compared to aspirin and statin alone for the primary endpoint was 0.51 (95% confidence interval [CI] 0.42-0.61). The HR for CV death was 0.62 (95% CI 0.46-0.85), non-fatal MI was 0.52 (95% CI 0.40-0.69), and non-fatal stroke was 0.35 (95% CI 0.23-0.54). The results were similar in sensitivity analyses. CONCLUSION: The estimated aggregate treatment effect of enhanced secondary prevention of ASCVD through comprehensive medical therapy is substantial. This exploratory analysis supports further study of comprehensive therapy to reduce residual CV risk for the secondary prevention of ASCVD.
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Ariss et al. (2022) conducted a meta-analysis in Atherosclerotic cardiovascular disease (ASCVD) (n=53,718). Icosapent ethyl, rivaroxaban, and ezetimibe added to aspirin and statin vs. Aspirin and statin alone was evaluated on Composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke (HR 0.51, 95% CI 0.42-0.61). Adding icosapent ethyl, rivaroxaban, and ezetimibe to aspirin and statins yielded an imputed HR of 0.51 (95% CI 0.42-0.61) for CV death, MI, or stroke in secondary ASCVD prevention.
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