Many physicians are finding themselves fielding a barrage of patient questions about heart disease this week due to headlines coming out of the American College of Cardiology's annual meeting in San Francisco. What has patients most concerned are results from the landmark HPS2-THRIVE study showing that niacin has dubious value in preventing heart disease and may even cause harm.
There had been high hopes for the extended-release niacin/laropiprant used in THRIVE. Studies showed it significantly raises high density lipoprotein (HDL) without causing the flushing that makes other forms of niacin difficult to tolerate.
And doctors like the idea of raising HDL with niacin. Spencer King, a colleague at Emory, said of niacin, "We have been pouring it on low HDL." The hope was that niacin would reduce the risk of cardiovascular events.
HPS2-THRIVE dashed that hope.
To recap, 25,673 high-risk patients were randomized to either placebo or Tredaptive (extended-release niacin plus laropiprant, an anti-flushing agent), in addition to background therapy with simvastatin or simvastatin/ezetimibe (Vytorin).
LDL levels dropped an average of 10 mg/dL and triglycerides fell 33 mg/dL. HDL levels increased 6 mg/dL. According to the study authors, "such lipid changes might translate into a 10% to 15% reduction in vascular events."
That didn't happen. Major vascular events -- a composite of nonfatal MI or coronary death, any stroke, or any arterial revascularization -- occurred in 13.2% and 13.7% of the niacin and placebo patients, respectively (P=0.29).
Worse, there were 31 serious adverse events for every 1,000 niacin-treated patients over 3.9 years of follow-up. And we're not talking about flushing: These were serious adverse events that led to people being hospitalized -- a significant increase in hemorrhagic stroke, serious infections, and new onset diabetes, as one researcher pointed out.
When your patients call, be prepared to spend some time talking with them. It will be time well spent. The lessons to be learned apply not only to this study, but others as well.
Merck has stopped all development of Tredaptive and pulled it from the market in Europe. But other formulations of niacin are still available. In fact, last year, 5.3 million prescriptions costing $1.1 billion were written for just one of those products, Niaspan, according to IMS data provided to the Milwaukee Journal Sentinel/MedPage Today.
The average patient might think, upon reading results of the THRIVE study, that the risks of niacin clearly outweigh the benefits when it comes to preventing heart disease. It's our job to explain that it's not that simple.
The findings are based on a large population study and, as such, tell us a whole lot about the population and very little about the individual patient.
Surrogate endpoints also deserve discussion. Patients might not understand biomarkers, but they know if they feel better. A growing number of medications -- even foods -- are being heavily marketed based on the fact they improve some surrogate measure of health such as blood cholesterol levels. But as THRIVE so clearly shows, what's the use of boosting HDL if it doesn't prevent heart attacks or death? Put in those terms, your patient will apply a new standard the next time he or she sees an ad shouting "This Product Improves Your Cholesterol!"
There are other things to discuss too. Will other HDL-boosting drugs work to prevent heart disease? That will have to await the results of ongoing trials of other HDL-raising agents -- anacetrapib and evacetrapib.
Meanwhile, Clyde Yancy, the former American Heart Association president who now heads cardiovascular medicine at Northwestern's Feinberg School of Medicine probably said it best: "We have drugs that work -- they are called statins. Why take chances on therapies that have no evidence of benefit?"
Finally, THRIVE offers yet another opportunity to drive home the fact that just because something is a vitamin or supplement, it isn't necessarily safe. No matter how many times we share that lesson, it keeps bearing repeating!