Icosapent ethyl may REDUCE CV risk in diabetes
Icosapent ethyl may reduce the risk of cardiovascular (CV) events in patients with diabetes mellitus (DM) taking statins, according to findings of REDUCE-IT DIABETES presented at ADA 2020.
“Statin-treated patients with DM are at high CV risk,” said Professor Deepak Bhatt from Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, US.
“[Results of this analysis showed that] icosapent ethyl at 4 g/day provides robust CV benefits in statin-treated patients with DM, with large relative and absolute risk reductions in both first and total CV events,” he said.
In the REDUCE-IT* trial, 8,179 statin-treated patients aged ≥45 years with either established CV disease (CVD) or DM plus other risk factors were randomized to receive icosapent ethyl (4 g/day) or placebo in addition to their statins.
Previous results showed that icosapent ethyl reduced the composite of CV death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina compared with placebo (primary endpoint; hazard ratio [HR], 0.75) as well as the composite of CV death, nonfatal MI, or nonfatal stroke (secondary endpoint; HR, 0.74; p<0.001 for both). [N Engl J Med 2019;380:11-22]
Of the total population, 58.5 percent had DM (n=4,787; median age 64 years, 36.1 percent female, 87.6 percent Caucasian, median HbA1c 7.0 percent). About 50 percent had established CVD, and 63.2 percent were on moderate intensity statins. Ninety-one percent of patients were on antidiabetes medications, with 49.5 percent on ≥2 medications. [ADA 2020, abstract 4-LB]
Consistent with the overall results, time to first and recurrent incidence of the primary composite endpoint was significantly reduced in icosapent ethyl vs placebo recipients (38.9 percent vs 51.6 percent; relative risk [RR], 0.77, 95 percent confidence interval [CI], 0.66–0.88; p=0.0003).
First and recurrent incidence of the secondary endpoint was also reduced with icosapent ethyl vs placebo (21.2 percent vs 30.1 percent; RR, 0.71, 95 percent CI, 0.60–0.84; p=0.00005).
There was a significant 24 percent reduction in first and subsequent primary endpoint events, accounting for 234 fewer CV events, with icosapent ethyl vs placebo (RR, 0.76, 95 percent CI, 0.65–0.88; p=0.0003).
The reduction with icosapent ethyl vs placebo was most evident in patients with established CVD and diabetes (58.0 percent vs 82.0 percent; RR, 0.70; p<0.00009) compared with those with diabetes and other risk factors but without established CVD (22.1 percent vs 25.4 percent; RR, 0.88; p=0.35) and those with established CVD but without diabetes (31.5 percent vs 53.3 percent; RR, 0.59; p=0.000000007).
“Patients with and without DM showed substantial benefits, but patients with DM had 1.5-fold greater rates of the primary endpoint in the placebo group, and a 7 percent absolute risk reduction in first and a 12.7 percent reduction in total events (both p<0.001) with icosapent ethyl,” said the authors.
Safety profiles were consistent with the main study. Atrial fibrillation/flutter occurred more frequently in icosapent ethyl than placebo recipients (3.5 percent vs 2.2. percent; p=0.01), as did bleeding (13.1 percent vs 10.9 percent; p=0.02), though serious bleeding did not significantly differ between groups (3.2 percent vs 2.5 percent; p=0.19).
“The reductions were consistent and robust across the prespecified hierarchy of endpoints, among patients with diabetes with or without CVD, as well as for those with established CVD and no diabetes at baseline,” noted Bhatt and colleagues. However, the study was not powered for subgroup analysis, nor was the presence of diabetes in established CVD a stratification factor, they said.
“[Regardless,] these data highlight the substantial impact of icosapent ethyl on the underlying atherothrombotic burden in the at-risk REDUCE-IT population, in those with [and] without DM,” they said.