Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT.
J Am Coll Cardiol. 2019 Mar 14;:
Authors: Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, Tardif JC, Gregson J, Pocock SJ, Ballantyne CM, REDUCE-IT Investigators
BACKGROUND: In time-to-first-event analyses, icosapent ethyl significantly reduced the risk of ischemic events, including cardiovascular death, among patients with elevated triglycerides receiving statins. These patients are at risk for not only first but also subsequent ischemic events.
OBJECTIVES: Pre-specified analyses determined the extent to which icosapent ethyl reduced total ischemic events.
METHODS: The Reduction of Cardiovascular Events with EPA-Intervention Trial (REDUCE-IT) randomized 8,179 statin-treated patients with triglycerides ≥135 and <500 mg/dL (median baseline of 216 mg/dL) and LDL-cholesterol >40 and ≤100 mg/dL (median baseline of 75 mg/dL), and a history of atherosclerosis (71% patients) or diabetes (29% patients) to icosapent ethyl 4g/day or placebo. The main outcomes were total (first and subsequent) primary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) and total key secondary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). As a pre-specified statistical method, we determined differences in total events using negative binomial regression. We also determined differences in total events using other statistical models, including Andersen-Gill, Wei-Lin-Weissfeld (Li and Lagakos modification), both pre-specified, and a post hoc joint-frailty analysis.
RESULTS: In 8,179 patients, followed for a median of 4.9 years, 1,606 (55.2%) first primary endpoint events and 1,303 (44.8%) subsequent primary endpoint events occurred (which included 762 second events, and 541 third or more events). Overall, icosapent ethyl reduced total primary endpoint events (61 versus 89 per 1000 patient years for icosapent ethyl versus placebo, respectively; RR 0.70, 95% CI 0.62-0.78, P<0.0001). Icosapent ethyl also reduced each component of the primary composite endpoint, as well as the total key secondary endpoint events (32 versus 44 per 1000 patient years for icosapent ethyl versus placebo, respectively, RR 0.72, 95% CI 0.63-0.82, P<0.0001).
CONCLUSIONS: Among statin-treated patients with elevated triglycerides and cardiovascular disease or diabetes, multiple statistical models demonstrate that icosapent ethyl substantially reduces the burden of first, subsequent, and total ischemic events.
PMID: 30898607 [PubMed - as supplied by publisher]