Test your knowledge of the key elements and outcomes of the highly buzzed about REDUCE-IT trial with this 5-question quiz.
Question 1. True or false? A 60-year-old woman presents with a history of DM, hypertension, and hyperlipidemia. Her fasting lipid panel shows an LDL-C of 90 mg/dL and TGs of 170 mg/dL; she has been on a stable dose of atorvastatin 40 mg daily for the past 3 months. This patient would have met inclusion criteria for the REDUCE-IT trial.
Answer: A. True. Patients were included in the study if they were aged ≥45 years with established CV disease or aged ≥50 years with DM and ≥1 additional risk factor; if they had a fasting TG level ≥150 and <500 mg/dL; an LDL-C level >40 mg/dL and ≤100 mg/dL on a stable statin Rx (± ezetimibe) for ≥4 weeks prior to randomization.
Answer: B. CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina (composite primary endpoint). The secondary endpoint was a composite of CV death, nonfatal MI, and nonfatal stroke; coronary revascularization and hospitalization for unstable angina were removed from the secondary endpoint. Median follow-up was 4.9 years.
Question 3. The study found that icosapent ethyl significantly lowered the risk of the primary composite endpoint vs placebo by which percentage?
Answer: D. 25%. Those who received 2g of icosapent ethyl twice daily had a 25% reduced risk of the primary composite endpoint vs placebo; 23% of the icosapent ethyl cohort reached primary endpoint vs 28.3% of the placebo cohort (HR 0.75, 95% CI, 0.68-0.83; NNT of 21). Furthermore, 16.2% of the icosapent ethyl cohort met the key secondary endpoint vs 20% of the placebo cohort (HR 0.74, 95% CI, 0.65-0.83; NNT of 28).
Question 4. There have been many questions about why this particular drug improved clinical outcomes when other omega-3 formulations have not. What makes icosapent ethyl unique in this study?
Answer: E. B and C. Standout results in REDUCE-IT have been attributed to the formulation and dose of the drug. The formulation of icosapent ethyl used in REDUCE-IT was a highly purified, stable EPA ethyl ester vs EPA/DHA combination that was used in JELIS. The total EPA dose was 4g daily vs 1.8g daily used in JELIS, however, both drug doses are still higher vs those used in prior trials.
Question 5. Which of the above is/are a putative mechanism/s by which icosapent ethyl may reduce the risk of CV events?
Answer: F. All of the above. Icosapent ethyl may have antioxidative, membrane-stabilizing, plaque-stabilizing, or anti-inflammatory properties; however, the precise mechanism of action is not known at this point. It is unlikely that it is purely due to TG lowering since the drug was effective regardless of baseline TG level or amount of TG lowering achieved. This observation may be confounded by the fact that TG levels tend to fluctuate, which makes it difficult to compare values at only 2 time points.
Reference: REDUCE-IT Investigators, Bhatt DL, Steg PG, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.
Concern over the persistent high rate of cardiovascular (CV) events among patients on preventive treatment and the prevalence of residual CV risk even among patients receiving appropriate statin treatment has long driven research to discover an effective adjunctive therapy.REDUCE-IT was a phase 3, randomized, double-blind, placebo-controlled trial that compared icosapent ethyl with placebo in the reduction of CV events.This short quiz tests your knowledge of key trial elements and outcomes.