November 10, 2018
REDUCE-IT Trial Evaluates Amarin's Vascepa for Reduction in MACE
November 10, 2018—Amarin Corporation plc announced that the results from the REDUCE-IT trial of cardiovascular outcomes of the company's Vascepa (icosapent ethyl) were presented as a late-breaking clinical trial at the American Heart Association (AHA) 2018 Scientific Sessions of held November 10–12 in Chicago, Illinois.
Deepak L. Bhatt, MD, who is Global Principal Investigator and Steering Committee Chair for the REDUCE-IT study, presented the findings. The results were simultaneously published online by Dr. Bhatt, MD, et al in The New England Journal of Medicine (NEJM).
REDUCE-IT was a global study of 8,179 adults with elevated cardiovascular risk comparing Vascepa 4 grams per day versus placebo over a median follow-up time of 4.9 years.
The REDUCE-IT study was designed under a special protocol assessment agreement with the FDA. Amarin intends to submit a supplemental new drug application to the FDA in early 2019 seeking approval to expand the label for Vascepa based on the cardioprotective effect of Vascepa demonstrated in the REDUCE-IT study.
Currently, Vascepa is FDA approved for use as an adjunct to diet to reduce triglyceride levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia.
According to Amarin, the results of REDUCE-IT confirmed multiple demonstrations of efficacy. Cardiovascular benefits appeared not to be influenced significantly by triglyceride levels at baseline (135–499 mg/dL baseline range) or as achieved at 1 year, suggesting mechanisms at work with the use of Vascepa that are independent of triglyceride reduction. Results were robust across multiple subgroups, including in patients with and without diabetes at baseline.
Efficacy results for Vascepa included achieving the study's primary endpoint:
- 25% relative risk reduction (RRR) (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.68–0.83; P < .001) in first occurrence of major adverse cardiovascular events (MACE, a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization) in the intent-to-treat population and unstable angina requiring hospitalization
Key secondary endpoint achieved:
- 26% RRR (HR, 0.74; 95% CI, 0.65–0.83; P < .001) in threepoint MACE in the intent-to-treat population
Additional secondary endpoints achieved include:
- Cardiovascular death or nonfatal heart attack: 25% RRR (HR, 0.75; 95% CI, 0.66–0.86; P < .001)
- Fatal or nonfatal heart attack: 31% RRR (HR, 0.69; 95% CI, 0.58–0.81; P < .001)
- Urgent or emergent revascularization: 35% RRR (HR, 0.65; 95% CI, 0.55–0.78; P < .001)
- Cardiovascular death: 20% RRR (HR, 0.80; 95% CI, 0.66–0.98; P = .03)
- Hospitalization for unstable angina: 32% RRR (HR, 0.68; 95% CI, 0.53–0.87; P = .002)
- Fatal or nonfatal stroke: 28% RRR (HR, 0.72; 95% CI, 0.55–0.93; P = .01)
- Total mortality, nonfatal heart attack, or nonfatal stroke: 23% RRR (HR, 0.77; 95% CI, 0.69–0.86; P < .001)
- Total mortality, including mortality from noncardiovascular and cardiovascular events: 13% RRR (HR, 0.87; 95% CI, 0.74–1.02; P = .09)
Excluding the MACE results described above, overall adverse event rates in REDUCE-IT were similar across the statin plus Vascepa and the statin plus placebo treatment groups. Positive REDUCE-IT results were consistent across various patient subgroups, including female/male, diabetic/nondiabetic, and secondary/primary prevention.
As noted by the investigators in NEJM, some of the reduction in MACE demonstrated by Vascepa in REDUCE-IT is likely explained by metabolic effects other than triglyceride lowering.
Dr. Bhatt stated, “REDUCE-IT establishes a new paradigm for the prevention of important cardiovascular events in statin-treated patients at elevated risk with increased triglycerides. I believe that the results of this study may represent the most significant breakthrough in preventative cardiovascular care since the introduction of statin therapy decades ago.” Dr. Bhatt is Professor of Medicine at Harvard Medical School, Executive Director of Interventional Cardiovascular Programs at Brigham and Women's Hospital Heart and Vascular Center in Boston, Massachusetts.