Icosapent ethyl reduces coronary revascularization in patients with high CV risk and elevated TG
Reduction in Revascularization with Icosapent Ethyl: Insights from REDUCE-IT REVASC.
Introduction and methods
Patients with hypertriglyceridemia while receiving statin treatment, have an increased risks of ischemic events, including coronary revascularization. Plus, elevated triglycerides (TG) levels are thought to play a role in the development and progression of coronary plaque and vessel inflammation contributing to residual coronary atherosclerosis [1-7]. However, previous clinical trials with TG-lowering agents, including omega-3 fatty acids, fibrates and niacin, have not demonstrated a consistent reduction in coronary revascularization events [8-12].
Previous analyses of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) have shown that icosapent ethyl reduced the occurrence of major cardiovascular events [13,14]. This study further assessed the effect of icosapent ethyl, compared to placebo, on coronary revascularization in participants of the REDUCE-IT, by evaluating all first coronary revascularization events, which included preoperative conditions and surgical procedure types.
The REDUCE-IT trial was a multicenter, double-blind, placebo-controlled, randomized trial with statin treated patients (≥50 years) with CVD, or diabetes with at least one additional CV risk factor, all with persistent elevated triglyceride levels (≥135 mg/dL and ≤500 mg/dL) and well-controlled LDL-c levels between 41 mg/dL and 100 mg/dL. Patients were randomized (1:1) to 4 gram icosapent ethyl daily or matching placebo. For this analysis, the primary endpoint was first coronary revascularization events, including the preoperative revascularization conditions (elective, urgent, emergent, or salvage) as well as categories of surgical procedures (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]). These revascularization endpoints were reviewed by blinded adjudicators. Median follow-up was 4.9 years.
- Icosapent ethyl significantly reduced the risk of first coronary revascularization compared to placebo (HR 0.66, 95% CI: 058-076, P<0.0001). There was a significant and sustained difference in treatment outcome for time to first coronary revascularization, already observed after 11 months. The NNT was 24.
- Patients treated with icosapent ethyl had a lower risk for first occurrence of emergent (HR 0.62, 95% CI: 0.42-0.92, P=0.016), urgent (HR 0.66, 95% CI: 0.54-0.79, P<0.0001), or elective revascularization (HR 0.68, 95% CI: 0.57-0.82, P<0.0001) compared to patients treated with placebo.
- There was a significant reduction in the number of patients in the icosapent ethyl group vs. placebo group that underwent PCI (7.7% vs. 10.9%; HR 0.68, 95% CI: 0.59-0.79, P<0.0001). Similar results were obtained for CABG (1.9% vs. 3.0%; HR 0.61, 95% CI: 0.45-0.81, P=0.0005).
- The number of total revascularization events (first and subsequent events) in the icosapent ethyl group was reduced by 36% compared to the placebo group, using a negative binomial model (RR 0.64, 95% CI: 0.56-0.74, P<0.0001). Other models produced similar results. When analyzing the distribution of reduction of first and subsequent revascularization, patients in the icosapent ethyl group had a 33% reduction in first revascularization events (P<0.0001), 51% in second (P<0.0001) and 50% in third or more events (P=0.04) compared to placebo.
In this subanalysis of the REDUCE-IT trial, icosapent ethyl additionally given to statins in high risk CV patients with persistent elevated TG levels reduced the risk for first and subsequent revascularization. This effect was consistent among different preoperative revascularization conditions, and PCI and CABG procedures.