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REDUCE-IT USA: Results From the 3146 Patients Randomized in the United States
Deepak L Bhatt1, Michael Miller2, Eliot A Brinton3
1Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA (D.L.B.).
Insights
Icosapent ethyl significantly reduced cardiovascular events in US patients, showing robust risk reductions in the REDUCE-IT trial. This finding supports its use for high-risk individuals, including all-cause mortality benefits.
Area of Science:
- Cardiovascular Medicine
- Clinical Trials
- Pharmacology
Background:
- Previous trials suggested varied patient responses to treatments based on geographic enrollment.
- The REDUCE-IT trial investigated icosapent ethyl for cardiovascular risk reduction.
- A subgroup analysis focused on US patients to clarify treatment efficacy within this population.
Purpose of the Study:
- To evaluate the specific benefits of icosapent ethyl in patients within the United States.
- To compare the efficacy of icosapent ethyl versus placebo in a US-based subgroup of the REDUCE-IT trial.
Main Methods:
- The REDUCE-IT trial randomized 8179 patients with high triglycerides and established cardiovascular risk factors.
- Participants received either icosapent ethyl (4 g/d) or a placebo.
- The primary composite endpoint included cardiovascular death, myocardial infarction, stroke, revascularization, or unstable angina hospitalization.
Main Results:
- A total of 3146 US patients were analyzed, representing 38.5% of the trial cohort.
- Icosapent ethyl significantly reduced the primary composite endpoint (HR 0.69) and key secondary composite endpoint (HR 0.69) in US patients.
- Robust risk reductions were observed for cardiovascular death, myocardial infarction, stroke, and all-cause mortality, with a significant interaction for all-cause mortality (P=0.02).
Conclusions:
- US patients in the REDUCE-IT trial experienced substantial cardiovascular risk reductions with icosapent ethyl.
- The findings indicate particularly robust benefits, including for all-cause mortality, in the US subgroup.
- Safety and tolerability profiles were consistent with the overall study population.
Background:
Some trials have found that patients from the United States derive less benefit than patients enrolled outside the United States. This prespecified REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial) subgroup analysis was conducted to determine the degree of benefit of icosapent ethyl in the United States.
Methods:
REDUCE-IT randomized 8179 statin-treated patients with qualifying triglycerides ≥135 and <500 mg/dL and low-density lipoprotein cholesterol >40 and ≤100 mg/dL and a history of atherosclerosis or diabetes mellitus to icosapent ethyl 4 g/d or placebo. The primary composite end point was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary composite end point was cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. A hierarchy was prespecified for examination of individual and composite end points.
Results:
A total of 3146 US patients (38.5% of the trial) were randomized and followed for a median of 4.9 years; 32.3% were women and 9.7% were Hispanic. The primary composite end point occurred in 24.7% of placebo-treated patients versus 18.2% of icosapent ethyl-treated patients (hazard ratio [HR], 0.69 [95% CI, 0.59-0.80]; P=0.000001); the key secondary composite end point occurred in 16.6% versus 12.1% (HR, 0.69 [95% CI, 0.57-0.83]; P=0.00008). All prespecified hierarchical end points were meaningfully and significantly reduced, including cardiovascular death (6.7% to 4.7%; HR, 0.66 [95% CI, 0.49-0.90]; P=0.007), myocardial infarction (8.8% to 6.7%; HR, 0.72 [95% CI, 0.56-0.93]; P=0.01), stroke (4.1% to 2.6%; HR, 0.63 [95% CI, 0.43-0.93]; P=0.02), and all-cause mortality (9.8% to 7.2%; HR, 0.70 [95% CI, 0.55-0.90]; P=0.004); for all-cause mortality in the US versus non-US patients, Pinteraction=0.02. Safety and tolerability findings were consistent with the full study cohort.
Conclusions:
Whereas the non-US subgroup showed significant reductions in the primary and key secondary end points, the US subgroup demonstrated particularly robust risk reductions across a variety of individual and composite end points, including all-cause mortality.
Clinical Trial Registration:
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01492361.
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