Reduce-It Usa

Abstract

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, P interaction =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.

Effects of Omega-3 Fatty Acid Supplements on Arrhythmias

“…1 However, recently, the REDUCE-IT trial of a 4 g daily dose of icosapent ethyl (a purified form of EPA) among participants with high triglycerides reported a highly statistically significant 25% proportional reduction in various cardiovascular outcomes. 2 The results in both low and high dose large trials are consistent with a pro rata to dose reduction in coronary heart disease events of 7-8% per 1 g EPA+DHA supplementation. 1,2 However, in REDUCE-IT, 2 supplementation was also associated with a nominally statistically significant (without adjustment for multiple comparisons) approximate 50% increase in hospitalisation for atrial fibrillation (AF) or flutter.…”

Effects and Issues of Diet Fat on Cardiovascular Metabolism

“…Whereas the replacement of SFA in the diet with MUFA increased CV events in some studies [74], other studies showed reduction [190] or no change [56,191] in CV events. As already described, one plausible The hazard ratios and 95% CI in the US and non-US population for the primary efficacy end point in REDUCE-IT study [186].…”

“…Recently, a subgroup analysis of REDUCE-IT study was conducted to determine the degree of benefit of EPA in the 3146 patients in the United States [186]. As shown in Figure 13, the US subgroup in REDUCE-IT demonstrated more robust risk reduction.…”

Effects of Eicosapentaenoic Acid on Arterial Calcification

“…The REDUCE-IT, a blinded RCT, also demonstrated that 4 g/day purified EPA reduced cardiovascular events: a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization and unstable angina for EPA vs. placebo was 17.2% vs. 22.0% [22,24]. However, the cardiovascular risk reduction was not associated with attainment of more normal triglyceride levels in REDUCE-IT [22].…”

“…In the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) and the Japan EPA Lipid Intervention Study (JELIS) using highly purified EPA, EPA significantly reduced the risk of cardiovascular events [22][23][24]. However, the effect of EPA on arterial calcification in a clinical situation is not established.…”