Icosapent ethyl therapy provides robust cardiovascular benefits in statin-treated adults with type 2 diabetes, with large relative and absolute risk reductions in first and total CV events, study data show.
In a prespecified analysis of the REDUCE-IT trial, researchers found that treatment with icosapent ethyl (Vascepa, Amarin) 4 g per day, compared with placebo, significantly reduced risk for the primary composite endpoint of CV death, myocardial infarction, stroke, coronary revascularization or unstable angina by 23% (HR = 0.77; 95% CI, 0.68-0.87) during a mean follow-up of 5.7 years, according to data from REDUCE-IT DIABETES reported at the virtual American Diabetes Association Scientific Sessions.
“It is well understood that people with diabetes have higher CV risk than those without diabetes,” Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, told Healio. “What may not be as well appreciated is that elevated triglycerides — irrespective of whether or not a person has diabetes, but especially with diabetes — are a powerful risk factor for increased risk of ischemic outcomes. That is even more the case if an individual has persistent elevation of triglycerides despite doing everything they can with lifestyle modification and are already prescribed maximally tolerated statin therapy. In this particular analysis, we see that we can substantially reduce that risk with icosapent ethyl.”
The multicenter, double-blind, placebo-controlled REDUCE-IT trial enrolled 8,179 patients (median age at baseline, 64 years; 71% men) who had fasting triglycerides of 135 mg/dL to 499 mg/dL and LDL levels ranging from 41 mg/dL to 100 mg/dL despite statin therapy and who had established CVD (70%) or diabetes plus other high-risk factors (30%). The primary results, published in The New England Journal of Medicine and first reported at the 2018 American Heart Association Scientific Sessions, demonstrated a 25% reduction in the primary endpoint of CV death, nonfatal MI, nonfatal stroke, coronary revascularization or unstable angina with icosapent ethyl vs. placebo (P = .00000001).
Within the REDUCE-IT cohort, 58.5% of participants had type 2 diabetes, with 91% prescribed at least one diabetes medication and 49.5% prescribed at least two diabetes medications.
Participants with diabetes had 1.5-fold greater rates of the primary endpoint vs. the placebo group, Bhatt said. Participants assigned icosapent ethyl experienced a 7% absolute risk reduction for a first CV event and a 12.7% absolute risk reduction in risk for total events compared with those assigned placebo (P < .001 for both).
Efficacy and safety were consistent with the full study, including reductions in secondary and tertiary endpoints and subgroups, and observed increases in atrial fibrillation/flutter (3.5% vs. 2.2%; P = .01) and bleeding (13.1% vs. 10.9%; P = .02) with icosapent ethyl vs. placebo, Bhatt said. Serious bleeding did not differ between groups (3.2% vs. 2.5%; P = .19). Fasting glucose and HbA1c levels remained stable through the duration of the trial, he said.
“What surprised me here was with the combination of diabetes and established CVD, event rates were astoundingly high,” Bhatt said. “What was striking was the absolute risk reduction for event rates were reduced from 40% to about 30% over about 5 years. A 10% absolute risk reduction is really quite large.”
Total ischemic event reduction
In analyses examining total ischemic events among participants with diabetes and established CVD, researchers observed a 30% RR reduction with icosapent ethyl vs. placebo, Bhatt said during an interview.
“In absolute terms, event rates were reduced by almost 25%. That is, by any standard, a pretty large absolute risk reduction,” Bhatt said. “It points to the fact that the combination of diabetes, elevated triglycerides and atherosclerosis is a really high-risk scenario. Even though the people in REDUCE-IT were stable outpatients — those who seemed deceptively stable in the office — if you follow them long enough, they have very high event rates in the placebo arm.”
Bhatt said the findings demonstrate that clinicians must be vigilant in screening for elevated triglycerides among patients, even if they seem stable.
In the setting of elevated triglycerides, “their cumulative risk for events is pretty high,” Bhatt told Healio. “That is true for diabetic primary prevention, it is true for those with established cardiovascular disease without diabetes, and it is true for those with atherosclerosis and diabetes.”