While statin therapy has proven highly effective in lowering cardiovascular risk among patients with elevated cholesterol, many patients remain at high risk due to increased triglycerides and triglyceride rich lipoproteins. Existing research suggests that triglyceride lowering may reduce cardiovascular event rates in patients with high triglyceride levels (>200 mg/dL). This unprecedented, five-year study will be the first large-scale randomized trial to directly test this hypothesis using a selective PPAR-a modulator in diabetic patients with high triglyceride levels.
“Epidemiologic, genetic, and mechanistic data all support a role for triglyceride-rich lipoproteins as important contributors to atherosclerosis. This trial, focusing specifically on high triglyceride patients with diabetes, will definitively test whether triglyceride reduction can reduce cardiac events” said Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at BWH and co-PI of the planned trial.
“We’ve been debating for years whether triglyceride lowering therapies added to a statin can further lower cardiovascular risk. Previous trials may have missed the mark by failing to focus on those with high triglyceride levels, the very patients most likely to benefit from this type of therapy” said Aruna Pradhan, MD, a cardiologist at BWH and co-PI of the planned trial.
An estimated 10,000 participants with diabetes and triglycerides >200mg/dL will be recruited worldwide. All patients will receive aggressive standard of care including maximally tolerated statin dosing and in addition, half will receive the selective PPAR-a modulator K-877 while the other half will receive placebo. The trial will include diabetic patients with and without established cardiovascular disease and will test whether K-877 reduces the occurrence of heart attacks, acute coronary syndromes requiring hospitalization for urgent revascularization, stroke, or death from cardiovascular causes.
Kowa Research Institute, Inc., a division of Kowa Company, Ltd. (Kowa), manufacturer of K-877 (pemafibrate), will sponsor the trial. Previous Kowa research has shown that this first in class selective PPAR-a modulator is more potent than currently available therapies in lowering triglycerides, ApoC3, and remnant cholesterol and increasing high-density-lipoprotein cholesterol.
Additional BWH researchers involved in the study include Peter Libby, MD who will serve as a scientific lead and Executive Committee Member; Nina Paynter, PhD who will lead the trial’s Data and Biostatistical Coordinating Center; Brendan Everett, MD who will head the Clinical Endpoint Coordinating Center; and Robert Glynn, ScD who will serve as the trial senior academic biostatistician
t Brigham and Women’s Hospital