Icosapent ethyl provides ‘consistent benefit’ in patients with, without prior PAD
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New analyses from the REDUCE-IT study show icosapent ethyl significantly reduced total primary CV endpoints by 32% in patients with prior peripheral artery disease, suggesting substantial benefit for a high-risk population.
The data were presented at the American Heart Association Scientific Sessions.
Patients with PAD are at very high ischemic risk; data from the REDUCE-IT trial show participants with a baseline history of PAD were much more likely to experience first and total primary endpoints over 5 years — a combination of CV death, MI, stroke, coronary revascularization and unstable angina — vs. those without baseline PAD.
“If you look at risk for total events among the patients with peripheral artery disease in REDUCE-IT, it is actually rather staggering, 98.2%,” Cardiology Today Intervention Section Editor Deepak L. Bhatt, MD, MPH, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, said in an interview. “What that tells us is, if you follow these patients long enough, even though all had well-controlled LDL cholesterol, were on a statin and other good background therapies, their event rates are so high. For those patients with elevated triglycerides and peripheral artery disease, it is a double whammy.”
As Healio previously reported, the main REDUCE-IT findings demonstrated icosapent ethyl (Vascepa, Amarin), a pharmaceutical-grade omega-3 fatty acid, was superior to placebo for reducing risk for ischemic events in patients with elevated triglycerides at high CV risk despite statin therapy. The study enrolled 8,179 patients (median age, 64 years; 71% men) who had fasting triglycerides 135 mg/dL to 499 mg/dL despite taking statins and who had established CVD (70.7%) or diabetes plus other risk factors (29.3%). Patients were assigned icosapent ethyl 2 g twice daily or placebo and followed for a median of 4.9 years.
The new REDUCE-IT analyses included a subset of 688 participants who had prior PAD assigned icosapent ethyl or placebo. The primary endpoint was time to CV death, MI, stroke, coronary revascularization or hospitalization for unstable angina. The key secondary endpoint was CV death, MI or stroke. Total (first plus recurrent) events were also assessed.
The primary endpoint event rate for patients with PAD was 26.2% with icosapent ethyl vs. 32.8% with placebo, for an HR of 0.78 (95% CI, 0.59-1.03; P = .08). Total events were 112.8 per 1,000 patient-years with icosapent ethyl vs. 162.3 per 1,000 patient-years with placebo, for an RR of 0.68 (95% CI, 0.48-0.95; P = .03).
Primary endpoint absolute risk reductions and numbers needed to treat suggested benefit for patients with PAD (absolute risk reduction, 6.6%; number needed to treat of 15) and without PAD (absolute risk reduction, 6.1%; number needed to treat of 16).
“The icosapent ethyl provides a benefit in this subgroup, as we have shown in other subgroups, so a consistent benefit as with the overall trial,” Bhatt told Healio. “But for those with prior PAD, there is a significant reduction with icosapent ethyl, but even there, total atherothrombotic events were 65.8% over 5 years. That is a high rate of ischemic events.”
Tolerability and adverse events were similar between the icosapent ethyl and placebo groups; more atrial fibrillation/flutter occurred with icosapent ethyl vs. placebo in patients with prior PAD (5.2% vs. 2.6%; P = .07).
Bhatt noted the new data included prespecified and post hoc analyses; REDUCE-IT was not powered for subgroup analyses and enrollment was not stratified by prior PAD.
“For those doctors who come across a patient with PAD and elevated triglycerides, these event rates are extraordinarily high and warrant aggressive risk factor modification,” Bhatt told Healio. “This is the patient who, in addition to icosapent ethyl, you want to rachet down the LDL, with polypharmacy if needed, and make sure blood pressure is under control. If they have diabetes, you also want to have tight glycemic control, assuming there are no contraindications.”
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Bhatt DL, et al. Presentation RF181. Presented at: American Heart Association Scientific Sessions; Nov. 13-15, 2021 (virtual meeting).
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