A review of REDUCE-IT data prior to an FDA supplemental new drug application decision shows the unprecedented benefit of the fish oil therapy.
Robert S. Busch, MD
Just this week, the US Food and Drug Administration (FDA) granted Priority Review to icosapent ethyl (Vascepa), the fish oil-based therapy seeking a supplemental indication for the reduction of residual cardiovascular risks in patients with elevated triglycerides.
When the FDA rules on the Amarin Corporation supplemental application in September, it will make its decision mostly based on the clinical results of the Vascepa CV Outcomes Trial (REDUCE-IT). As a recent review of the long-term, 8000-patient study showed, oral icosapent’s potential in cardiovascular risk reduction may be unprecedented.
The Amarin-supported review, presented at the American Diabetes Association (ADA) 2019 Scientific Sessions in San Francisco, CA, by Robert S. Busch, MD, director of Clinical Research at Albany Medical College, discussed the REDUCE-IT findings both as they pertain to the supplemental application for icosapent as well as its current adjunct hypertriglyceridemia treatment indication.
“Like many of you, I see patients every day,” Busch told his audience at ADA. “And this will change what you do Wednesday morning when you’re back at work.”
It’s fairly common for patients with type 2 diabetes (T2D) to present with raised triglyceride counts routinely, Busch said, requiring physicians to have a viable treatment regimen to manage patient symptoms and elevated cardiovascular risks alongside statins.
In the REDUCE-IT trial—previously presented at the American Heart Association (AHA) 2018 Scientific Sessions—investigators led by Deepak L. Bhatt, MD, MPH, of the Brigham and Women’s Hospital Heart and Vascular Center enrolled 8179 patients with established cardiovascular disease or with diabetes plus other risk factors.
Patients were required to have been receiving statin therapy, as well as a fasting triglyceride level of 135-499 mg per deciliter and a low-density lipoprotein cholesterol level of 41-100 mg per deciliter at baseline.
While assessing for a primary endpoint of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina, investigators randomly assigned patients to either twice-daily 2 g icosapent ethyl or placebo.
The team also assessed for a key secondary endpoint of composite cardiovascular death, nonfatal MI, or nonfatal stroke.
Primary endpoint event occurred in significantly fewer treated patients (17.2%) than placebo patients (22.0%; HR .75; 95% CI: .65 - .83; P< .001), and the key secondary endpoint was also reached in fewer treated patients (11.2%) than placebo patients (14.8%; HR .74; 95% CI: .65 - .83; P< .001).
Additional ischemic endpoints were also significantly lower in patients treated with icosapent, including the rate of cardiovascular death (4.3% vs 5.2%; HR .80; 95% CI: .66 - .98; P= .03).
A greater rate of patients administered icosapent were hospitalized for atrial fibrillation/flutter, or reported serious bleeding events.
When recounting the significance of the findings, Busch noted the critical need for cardiovascular disease and mortality prevention—at a time when diabetes is reaching epidemic levels, and annual heart disease-driven deaths are climbing. And though much trial data—including those being presented at ADA 2019—evidences better lowering and management of LDL-C with statin monotherapy, residual risk remains unaddressed.
With raised triglyceride levels serving as a reliable indicator of increased cardiovascular risk, clinicians are seeking therapies that capably treat both triglyceride counts and prevent cardiovascular outcomes.
As such, repeated findings showing that icosapent significantly betters both these rates in statin-treated patients has led to broader recognition. The ADA’s 2019 Standards of Care in Diabetes included REDUCE-IT findings to support its designation of icosapent ethyl as an advised treatment for cardiovascular risk reduction among patients with atherosclerotic cardiovascular disease, diabetes, statin-controlled LDL-C, and raised triglyceride levels.
“It’s an obligation and a new standard of care from the ADA to know the triglyceride level in at-risk patients,” Busch said. “And if it’s raised, it’s also now an obligation to prescribe icosapent.”
Busch closed noting that icosapent was associated with “unprecedented” cardiovascular event risk reductions. Whether that’s reflected in the FDA’s decision to support or reject the therapy’s indication will be known in only a few months.