Preventive Cardiology and Pemafibrate Study

In preventive cardiology work up, measuring levels of triglycerides is a routine affair and lowering triglycerides with several classes of drugs is common medical practice.

Researchers have found in the PROMINENT trial that the novel drug pemafibrate lowered triglycerides but did not cut the incidence of cardiovascular (CV) events compared with placebo in patients with type 2 diabetes and mixed dyslipidemia. Further researchers found no reduction in rates of heart attack, stroke, or cardiovascular death over a five-year period, despite the drug lowering triglycerides by 26 percent compared to placebo.

Investigators at Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, included more than 10,000 participants. The new data of the study was presented at the annual meetings of the American Heart Association Scientific Sessions and published simultaneously in the New England Journal of Medicine.

"Pemafibrate was highly effective at lowering triglycerides and what we call remnant cholesterol," said lead author Aruna Pradhan, MD, MPH, of the Brigham's Division of Cardiovascular Medicine, who served as the trial co-chair. "Yet we saw no evidence of a reduction in the hard clinical events that patients and clinicians worry about. These findings are both puzzling and clinically important."

PPARα agonists like fibrates are a class of drugs that reduce the level of triglycerides in the bloodstream through several mechanisms. Pemafibrate, developed by Kowa Company, Ltd as a selective PPARα modulator (SPPARMα), is licensed for use in Japan and some other Asian countries; conventional fibrate drugs such as fenofibrate are approved for use around the world including the U.S.

The clinical trial, known as PROMINENT and by the Kowa Research Institute, Inc., included 10,497 patients who had type 2 diabetes, increased levels of triglycerides, and low levels of HDL-cholesterol—a group that had shown promising results in fibrate trials performed a decade ago. However, the PROMINENT trial primary endpoint of heart attack, stroke, need for coronary bypass or angioplasty, or cardiovascular death occurred in 572 participants randomly assigned to pemafibrate and 560 assigned to placebo, resulting in no statistical difference between groups. Pemafibrate, however, was generally well-tolerated and appeared to reduce rates of non-alcoholic fatty liver disease (NAFLD), an important condition among individuals with diabetes and obesity.

Reference

• Aruna Das Pradhan
• Robert J. Glynn
• Jean-Charles Fruchart
• Jean G. MacFadyen
• Elaine S. Zaharris
• Brendan M. Everett
• Stuart E. Campbell
• Ryu Oshima, R.Ph.
• Pierre Amarenco
• Dirk J. Blom
• Eliot A. Brinton
• Robert H. Eckel
• DOI: 10.1056/NEJMoa2210645