People who take the recently approved blood-thinning medication dabigatran could have a slightly increased risk of heart attack compared with people who use the old standby drug warfarin, new research suggests.
When dabigatran was approved in 2010, it became the first new medication for blood-clot prevention in about 50 years. Sold under the brand name Pradaxa, dabigatran has been taken by an estimated 500,000 people to prevent blood clots that could cause stroke.
The drug is primarily given to patients with atrial fibrillation, who are at higher risk for this kind of stroke, as well as to patients undergoing joint replacement and other surgeries, to prevent blood clots.
But the fanfare over dabigatran's approval has been clouded somewhat by lingering questions over its effects on the heart. Several clinical trials showed a slightly increased risk of heart attacks in people who took the drug compared with people taking warfarin, but a reanalysis of the data at the request of the Food and Drug Administration concluded there was no statistically significant increased risk.
The new paper, published online Monday in the Archives of Internal Medicine, sought to clarify the situation, said lead author Dr. Ken Uchino, a neurologist at the Cleveland Clinic in Ohio. It pooled data from seven studies — involving 30,514 people — that compared dabigatran to warfarin, the injected blood-thinner enoxaparin or a placebo. Most of the data came from the same clinical trials that had earlier led to approval of dabigatran, called the RE-LY studies.
Rates of heart attack or angina (chest pain caused by oxygen deprivation to the heart) were increased 33% in dabigatran-takers, although the risk remained very small: Only 237 heart-related events — 1.19% — occurred among 20,000 dabigatran users, compared with 0.79% of people taking another drug or a placebo, Uchino said.
It's unclear what causes the elevated risk seen in patients taking dabigatran compared with warfarin, said Dr. Stuart J. Connolly, director of the division of cardiology at McMaster University in Canada, who was lead investigator on the RE-LY studies. One possibility is that warfarin confers some heart benefits that dabigatran lacks, he said.
"When we say that dabigatran has a higher risk of myocardial infarction [heart attack] than warfarin, that doesn't mean dabigatran is causing myocardial infarction," Connolly said. "It just means — and evidence is supporting this view — that warfarin is reducing myocardial infarction compared to dabigatran."
But Dr. Jeremy M. Jacobs, a senior physician at Hadassah Hebrew University Medical Center in Jerusalem, said doctors should ratchet down their enthusiasm for dabigatran until more research can be done to clarify the potential heart attack risk.
"I think caution is needed, especially among patients with known active ischemic heart disease," said Jacobs, who co-wrote an editorial published with the report.
Recent history has taught medical professionals that the full effects of a new medication may not be apparent until it is in widespread use — sometimes years after FDA approval, Jacobs said. For example, the painkiller Vioxx was on the market for almost five years before it became clear that it was associated with an increased risk of heart attacks and strokes; it was withdrawn in 2004.
Still, the possible link between dabigatran and heart attacks is far from settled. In another paper designed to look only at people with atrial fibrillation that was published online last week in the journal Circulation, the RE-LY investigators found no significant increased risk of heart problems in dabigatran users.
The study concluded that dabigatran is superior to warfarin in people with atrial fibrillation when looking at the overall incidence of strokes, blood clots, heart attacks, bleeding and other problems.
Connolly and Uchino said the risk-benefit balance still appeared to be in favor of dabigatran, which is preferred by many doctors because warfarin can cause serious bleeding and patients taking it need close monitoring.
"I think we have to keep in mind all drugs have potential side effects, and it's always a question of benefit and harm," Uchino said.