March 9th, 2013
HPS2-THRIVE: A ‘Disappointing But Clear’ Result
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The results of HPS2-THRIVE were “disappointing but clear,” said Jane Armitage, who presented the results this morning at the ACC meeting in San Francisco.
HPS2-THRIVE randomized 25,673 high-risk patients who could tolerate niacin to either placebo or extended-release niacin plus laropiprant (Tredaptive, Merck), an anti-flushing agent, in addition to background therapy. The primary endpoint was the time to first major vascular event, defined as the composite of non-fatal MI or coronary death, any stroke, or any arterial revascularization.
Major vascular events occurred in 13.2% of the niacin arm and 13.7% of the placebo arm (p=0.29), despite causing average reductions in LDL of 10 mg.dL and triglycerides of 33 mg/dL, in addition to a 6 mg/dL increase in HDL. Armitrage reported that based on data from previous trials and observational studies, “it was anticipated such lipid differences might translate into a 10-15% reduction in vascular events.”
Significantly more patients in the niacin arm stopped their study treatment during the course of the trial (25.4% versus 16.6%). Serious adverse events also occurred more often in the niacin group, including new onset diabetes (9.1% vs. 7.3%), diabetic complications (11.1% vs. 7.5%), gastrointestinal problems (4.8% vs. 3.8%), and skin problems such as itching and rashes (0.7% vs. 0.4%).
The investigators were also surprised to find higher rates of bleeding (2.5% vs. 1.9%) and infections (8.0% vs. 6.6%) in the niacin group. They offered no explanation for these findings.
“We are disappointed that these results did not show benefits for our patients,” said Jane Armitage, lead author of the HPS2-THRIVE study, in a press release. “Still, finding out a drug is not helping people is just as important as finding that it has benefits — the net result is that people are healthier. Niacin has been used for many years in the belief that it would help patients and prevent heart attacks and stroke, but we now know that its adverse side effects outweigh the benefits when used with current treatments.”
Armitage said that the trial results are unlikely to be due to the side effects of laropriprant, since the main finding of a lack of benefit is consistent with the AIM-HIGH study and many of the side effects are known to be associated with the use of niacin.
During the panel discussion Donna Arnett noted that the trial was performed in a patient population that had already achieved low LDL levels with statins. The results of HPS2-THRIVE establish that “if you have a low LDL on a statin there is no benefit” with niacin. “So it really is calling into question whether raising HDL in the context of low LDL is important,” she said.
Another panelist, Christie Ballantyne, agreed with Arnett, and went further, arguing that the study did not shed light on the patient population that is most likely to take niacin. He said the majority of niacin patients in the U.S. have LDL levels over 70. He said it was still possible that niacin could be found beneficial in this group.