REDUCE-IT finds medication added to statins reduces risks among patients with high triglycerides

Primary results from the REDUCE-IT study found that supplemental icosapent ethyl, a prescription medication approved to reduce triglycerides ≥ 500 mg/dL, significantly reduced the risk of important cardiovascular events by 25 percent. This includes a 31 percent reduction in myocardial infarction, a 28 percent reduction in stroke and a 20 percent reduction in death due to cardiovascular causes in statin-treated men and women with hypertriglycemia.

“We hope REDUCE-IT will transform the care of millions of patients worldwide,” said Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital in Boston, who presented the findings at Scientific Sessions 2018 in Chicago.

REDUCE-IT randomized more than 8,000 patients with well-controlled LDL-cholesterol on statins for secondary or primary prevention who had triglycerides between 135-500 mg/dL to icosapent ethyl versus placebo and followed them for an average five years.

Previous trials of low-dose triglycerides have shown no CV benefit. However, the JELIS trial, in which Japanese hypercholesterolemic patients received low-dose (1.8 g/day) eicosapentaenoic acid, suggested a 19 percent CV risk reduction. “That led us to the REDUCE-IT trial,” Bhatt said.

Icosapent ethyl is a highly purified ethyl ester of EPA available by prescription that lowers triglyceride levels and also has anti-oxidative, anti-inflammatory and other potentially anti-atherogenic properties. Bhatt and his colleagues sought to evaluate whether icosapent ethyl would reduce ischemic events in patients at elevated cardiovascular risk concurrently treated with statins.

In the international, multicenter, prospective, randomized, double-blinded, placebo-controlled, parallel group trial of stable statin therapy, study subjects took 4 grams/day of icosapent ethyl or placebo. That dose was chosen because it has been tested and is used most commonly, Bhatt said.

Inclusion criteria for REDUCE-IT was broad: men and women ≥ 45 years with established cardiovascular disease or ≥ 50 years with diabetes in combination with one additional risk factor for cardiovascular disease. Fasting triglycerides levels ≥ 150 mg/dL and < 500 mg/dL were required. LDL-cholesterol levels needed to be > 40 mg/dL and ≤ 100 mg/dL, with patients on statin therapy (± ezetimibe) for ≥ 4 weeks before the LDL-cholesterol and triglyceride qualifying measurements for randomization.

Although icosapent ethyl was well tolerated, study subjects experienced a small but significant risk of atrial fibrillation. “That side effect might have worried me, but we saw a 28 percent reduction in stroke, which is the worst thing that AFib could do,” Bhatt said. “I wouldn’t not use icosapent ethyl in a REDUCE-IT population because of the risk of AFib.” Bhatt cautioned, however, that icosapent ethyl should not be confused
with OTC omega-3 supplements. Most OTC omega-3 supplements contain DHA and EPA, and they are not highly purified, he said. Patients shouldn’t think they can take an over-the-counter omega-3 supplement and receive the same potent benefit of prescription icosapent ethyl, Bhatt said.

Despite the demonstrated clinical benefits of lowering LDL-C with statins, significant residual cardiovascular risk remains for statin-treated patients.

REDUCE-IT has the potential to offer a new standard of care for patients with elevated triglycerides at increased cardiovascular risk despite statin therapy.

In an initial smartphone poll in Saturday’s session, 65 percent of participants said they don’t regularly prescribe triglyceride lowering drugs in high-risk patients with moderate hypertriglyceridemia (200-500 mg/dL). After Bhatt’s REDUCE-IT presentation, 89 percent indicated they would.