Last week, the National Institutes of Health called an abrupt end to a medical trial expected to confirm a method doctors have already been using to combat heart disease: combining drugs to raise good cholesterol with those that lower bad cholesterol. But, the trial didn’t go at all as expected. Only a little over halfway through the five-year plan, the NIH called it off.
The surprise was that adding high-powered niacin to raise good cholesterol (HDL) didn’t show any added benefit for coronary artery disease patients already on statin drugs that lower bad cholesterol (LDL). There was also a slightly increased risk of stroke for those taking both the niacin drug (Niaspan) and the potent statin (Zocor).
The results were disappointing to many in the field and the increased risk of stroke was especially disturbing. “It’s very puzzling and unexpected. You’ve got to look at it as a statistical anomaly … a play of chance,” said Dr. William Boden, one of the principal investigators of the trial. He is also professor of medicine and preventative medicine at the University of Buffalo Schools of Medicine and Public Health. “No one can define a plausible explanation.”
That’s partially because niacin, a form of vitamin B, is known to decrease risk of stroke, not increase it. Niacin has been used for treating heart disease since the 1950s, when a large study showed it increased good cholesterol and lowered blood fats called triglycerides. In recent years, doctors have been matching it up with statins, which lower LDL, or bad cholesterol, pretty regularly. So, the study seemed a shoe-in for success.
The unexpected non-result has some other doctors in the field saying it might be the way the trial was done and not the drugs themselves.
“Niacin is best used for people who haven’t reached LDL targets,” said Dr. Antonio Gotto, dean of the Cornell-Weill Medical College and a leading expert in heart disease and blood lipids like cholesterol. Gotto said the patients in the study were already using statins that kept their bad cholesterol down to low levels, below 80 mg/dL. The doctors who investigated the trial also said that could have been a problem.
“Statins are the most significant drugs that have been developed yet for reducing coronary artery events,” said Gotto. “You’re adding a high bar when you have to show an effect over and above statins.”
He believes the study was “underpowered,” with too few participants and no true placebo since all the patients were taking a statin. Another, similar study in progress at Oxford University has 25,000 people and is using much higher doses of niacin. When that study is complete, Gotto said, doctors will have a better idea of how niacin and statins work for different heart disease cases.
What this surprising outcome doesn’t change is research that says people with low bad cholesterol and high good cholesterol have a much lower risk of heart disease. The trick is to find therapies that do both those things and effectively work to reduce coronary “events.” Doctors say medicine hasn’t gotten there yet.
Adding HDL therapy for those who already have low LDL cholesterol may not have helped, but doctors say niacin is still very useful for reducing blood triglycerides and boosting HDL cholesterol.
Naturally occurring vitamin B3 in food or a daily allowance of niacin supplements can provide a modest boost in HDL to those who have borderline low levels. But, for most coronary artery disease patients who need a major change, doctors are still likely to recommend super-powered prescription niacin that’s 100 times the dose of a multivitamin, like Niaspan. That hasn’t changed.
“Is this lights out for niacin or Niaspan? I’d say no,” said Boden. He added, “If you have LDLs well-controlled, maybe you shouldn’t be taking niacin. Patients with acute coronary disease or acute heart attack, that’s a group we need to study.”