While pemafibrate reduced triglycerides, very-low-density lipoprotein (VLDL) cholesterol, remnant cholesterol, and apolipoprotein C-III (ApoCIII) among adults with type 2 diabetes, it did not reduce rates of cardiovascular events in these patients, according to findings from the PROMINENT trial presented at the American Heart Association annual meeting and published in the New England Journal of Medicine.
In this exclusive MedPage Today video, Aruna D. Pradhan, MD, MPH, MSc, of Brigham and Women’s Hospital in Boston, discusses the results.
Following is a transcript of her remarks:
We began this study over 7 years ago — as you know trials take a long time to plan — but the premise was that using the strategy of peroxisome proliferator-activated receptor (PPAR)-alpha agonism, but now with a more potent agent, pemafibrate, in a population that was shown in prior clinical trials of the fibrate-like drugs to have benefit, might reduce cardiovascular risk in patients with diabetes, mild to moderate hypertriglyceridemia, and low HDL levels.
And so the prior data from five landmark trials had told us that if we enrolled this type of population with mixed dyslipidemia, that we’d get about a 35% risk reduction. And really the pivot was around going to a population with hypertriglyceridemia as opposed to all patients and treating them with a PPAR-alpha agonist. So we enrolled this population, over 10,000 patients around the globe, and we ensured that they had a high rate of background statin use. We really wanted to test a new agent based upon current standard of care and I think we achieve that.
I think there has been some misinterpretation in social media and the media networks. The results were that at a median follow-up of 3.4 years, there was no risk reduction in terms of cardiovascular events. The hazard ratio was right about 1.0. We had over 1,100 events, so we were powered, well powered. Our DSMB [data and safety monitoring board] had stopped the trial after the 75% interim analysis. They’d been looking the entire way and seeing no separation of the curve, so the trial was terminated early.
What we also found is that the drug, as expected, was efficient in lowering triglyceride levels. There was a 25% reduction in triglyceride levels, a 25% reduction in VLDL (very-low-density lipoprotein), remnant cholesterol, which we think is a cholesterol attached to degraded triglyceride-rich lipoproteins, and then also ApoCIII, which the genetics told us was good. It should have conferred a benefit. We had 25% across the board on all those four markers, but we also had an increase in LDL cholesterol, about 12% or so, and a 5% increase in ApoB [apolipoprotein B-100] with no change in non-HDL [high-density lipoprotein] cholesterol.
There were some other interesting findings. We can talk about the impact on liver disease in the trial. There was a signal for some benefit there. It was an exploratory analysis. We did not do the rigorous validation during the course of the trial, but we’re doing some of that validation now retrospectively to tease out that signal a bit more.
Source: MedicalNewsToday.com
