Deepak L. Bhatt, MD, MPH, the executive director of Interventional Cardiovascular Programs at the Brigham, was on a plane when the news broke: the U.S. Food and Drug Administration (FDA) had approved the use of Vascepa (icosapent ethyl) to reduce the risk of cardiovascular events among adults with elevated triglyceride levels (a type of fat in the blood) and other risk factors for heart disease. The December announcement followed the FDA advisory panel’s unanimous vote for this approval in November. The drug was previously approved for people with very high triglyceride levels (≥ 500 mg/dL), but the new approval greatly expanded the potential pool of patients eligible to take the drug. The announcement is the latest ripple effect of the results of REDUCE-IT, a clinical trial led by Bhatt that piqued the interest of the cardiology community and may change the practice of preventive medicine.
“The REDUCE-IT results illustrate how the prescription medication icosapent ethyl could transform the treatment of cardiovascular disease in the United States and worldwide,” says Bhatt. “From my perspective, as not only a researcher but also a practicing physician, icosapent ethyl represents one of the most important developments in the prevention and treatment of cardiovascular disease since statins, and it will be a critical tool for physicians to use to help prevent cardiovascular events such as heart attack and stroke, including fatal ones, in high-risk patients.”
Icosapent ethyl is a pure and stable prescription form of the omega-3 acid known as EPA. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT), sponsored by the pharmaceutical company Amarin, included more than 8,000 patients with well-controlled LDL-cholesterol who were taking statins to prevent a first or subsequent cardiovascular event. Patients in the study had triglyceride levels that were at least borderline high (135 mg/dL) and other cardiovascular risk factors. Approximately 70 percent of patients in the study had established atherosclerosis and the rest had diabetes plus at least one other cardiovascular risk factor. Patients were randomized to receive either 2 grams of icosapent ethyl (Vascepa capsules, manufactured by Amarin) twice daily or a placebo, and were followed for an average of approximately five years.
At the 2018 American Heart Association Late-Breaking Clinical Trial Session, Bhatt presented the results, which were simultaneously published in The New England Journal of Medicine. Icosapant ethyl reduced the risk of cardiovascular events by 25 percent, including a 20 percent reduction in death due to cardiovascular causes, a 31 percent reduction in heart attack, and a 28 percent reduction in stroke.
Bhatt described the results as “remarkable.”
“This may be the biggest development in cardiovascular prevention since statins. The REDUCE-IT trial sets a new standard of care for these patients,” he said.
As stated in the FDA press release, icosapent ethyl “is the first FDA approved drug to reduce cardiovascular risk among patients with elevated triglyceride levels as an add-on to maximally tolerated statin therapy,” signifying a major milestone in medicine. The American Heart Association listed this approval based on REDUCE-IT as one of the 2019 Top Heart Disease and Stroke Research Advances, placing it among studies the selection committee called “momentous for our patients.” Clinicians in the field have responded with enthusiasm to the results. Worldwide guidelines, including from the American Diabetes Association, the European Society of Cardiology, the European Atherosclerosis Society, and the National Lipid Association, have rapidly incorporated the findings.
In March of 2019, Bhatt presented results looking beyond a patient’s first cardiovascular event, expanding the scope of the projected protective effects of the drug. As a Late-Breaking Clinical Trial at the American College of Cardiology Annual Meeting, he reported that compared with placebo, icosapent ethyl provided a 30 percent relative risk reduction in total (first and subsequent) cardiovascular events. The tfindings were published simultaneously in the Journal of the American College of Cardiology. And published very recently in Circulation were the REDUCE-IT results for the over 3,000 patients from the USA, showing large reductions in cardiovascular events, including a 30 percent reduction in mortality.
“This is a new additional lipid-lowering therapy that goes beyond our usual approach of lowering LDL (bad) cholesterol,” said Christopher P. Cannon, MD, education director for cardiovascular innovation at the Brigham. “For patients who have cardiovascular disease or diabetes and higher cardiovascular disease risk, the benefits of adding icosapent ethyl were amazing and big. I now look to add this in all patients who meet the criteria, and I am thrilled to be able to further lower risk by 25 percent.”
Clinical Trial Expertise
Bhatt’s academic leadership in designing and carrying out the REDUCE-IT trial extends the Brigham’s Heart & Vascular Center’s legacy of clinical research. Brigham investigators in the Heart & Vascular Center remain committed to catalyzing advancements in care through research, including randomized, placebo-controlled clinical trials. In 2014 alone, Brigham cardiovascular researchers were responsible for 281 active clinical trials, with over 100,000 study participants worldwide.
Over the years, clinical trials led by Brigham Heart & Vascular investigators have demonstrated that:
- Thrombolytic therapy (clot-busting drugs) could significantly improve a patient’s chance of survival following a heart attack
- Aspirin could prevent a first heart attack
- ACE inhibitors could save lives and protect against left ventricular enlargement following a heart attack, and cholesterol-lowering medication could save lives in patients following a first heart attack.
View the Heart & Vascular Center’s timeline of innovation and discovery here.