Peter Libby, MD, a cardiovascular medicine specialist, Brigham and Women’s Hospital, and Mallinckrodt Professor of Medicine, Harvard Medical School, explains the takeaways from the PROMINENT trial using pemafibrate to lower cardiovascular risks. The trial, presented at the American Heart Association (AHA) 2022 meeting, did not show reduction in the incidence of cardiovascular events among those who received pemafibrate than among those who received placebo.
During the statin era, fibrates did not perform that well, but there was still a belief these agents could help further reduce cardiovascular risks in select patients. So Libby worked with key Harvard cardiovascular researchers Aruna Das Pradhan and Paul M Ridker to create a trial to test if pemafibrate could help lower cholesterol levels further.
"We designed what we thought would be the right study," Libby explained. "We thought we had a good drug and we took all the people that the post-hoc analysis of vibrate trials in the statin era suggested should benefit. This study was conducted impeccably well despite the pandemic, but we were extraordinarily disappointed that the study was a clean null."
High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator–activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. The trial recruited 10,497 patients.
Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol and apolipoprotein C-III levels.
"We are in a more perplexing place post-AHA than we where we hoped to be before in the treatment of triglycerides," Libby said. "I am convinced from the human genetic evidence and the observational epidemiology that triglyceride-rich lipoproteins are causal in human athro-thrombosis. But what do we do about it? So, we are back to square one, and we don't have much to offer patients today."
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com