What do you do when the cat is let out of the bag, and has been for several months? That is the quandary facing the American College of Cardiology (ACC) with one of its late-breaking clinical trials.
Last December, HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) sponsor Merck announced that the trial had missed its primary endpoint. The study was designed to evaluate extended release niacin and laropiprant in addition to statins in patients who are at high risk of major vascular events.
More than 25,000 patients were followed for a median of 3.9 years. Merck announced that adding its combo drug failed to significantly further reduce the risk of the combination of coronary deaths, nonfatal MIs, strokes or revascularizations compared to statin therapy alone.
In a study published this week in the European Heart Journal, HPS2-THRIVE researchers reported more bad news: About one-quarter of participants in the study’s niacin/laropiprant arm decided to stop taking the drug, mostly due to side effects. Keep in mind that in a prerandomization run-in phase, one-third of the original cohort was excluded, with most citing intolerable side effects from the niacin/laropiprant therapy. Researchers also reported a four-fold excess risk of myopathy in patients taking the combo therapy, and the risk was 10 times higher for patients in China compared with Europe.
HPS2-THRIVE is one of two studies opening the show on March 9 as late-breaking clinical trials at ACC.13 in San Francisco. That begs the question: Given that we already know the trial missed its primary endpoint, what is there to learn? Perhaps a good deal, it turns out.
In their European Heart Journal paper, the researchers wrote that based on patients’ lipid changes seen in the run-in phase, “it was estimated prior to unblinding the trial that study average differences in LDL-C [low-density lipoprotein cholesterol] of approximately 0.25 mmol/L and HDL-C [high-density lipoprotein cholesterol] of approximately 0.13 mmol/L would have been achieved.”
In a preview of the late-breaking clinical trials, ACC.13 Co-Chair Christie Ballantyne, MD, emphasized the rich data that HPS2-THRIVE offers. A trial that enrolled such a large number of participants would be sufficiently powered to allow analyses of subgroups, said Ballantyne, who is also chief of cardiology at Methodist DeBakey Heart Center in Houston. That may give physicians an insight on the use of niacin with patients who have high LDL-C or low HDL-C, for instance.
Time will tell, and that time is approaching quickly. Please let us know what you are eager to learn from ACC.13. We will look forward to providing you with daily coverage.
Cardiovascular Business , editor