An experimental blood thinner called rivaroxaban is at least as good at preventing strokes as the old warhorse warfarin, which has been used for decades in people with erratic heartbeats, researchers said Monday. The drug also sharply reduces the risk of major bleeding that is seen with warfarin.
Rivaroxaban and the recently approved Pradaxa offer alternatives to the widely used warfarin, which frequently has unforeseeable interactions with food and people of certain genetic types and requires monthly laboratory tests to ensure safety.
An estimated 2.3 million Americans suffer from atrial fibrillation, in which the heart beats erratically and cannot pump blood effectively, causing blood clots to form. Most people with atrial fibrillation could benefit from the new drugs, experts said, and analysts estimate the market for drugs in this class could top $20 billion a year.
"Both of these drugs are game-changers, I think," said Dr. Douglas Zipes of the Indiana University School of Medicine, a former president of the American College of Cardiology who was not involved in the research.
Both heart rate and the rhythm of heartbeats are important in predicting survival, Zipes said. "It's very easy to give a beta blocker to control rates," he added. "Now we have a once-a-day drug to control [problems caused by] rhythm, giving us very simple, straightforward treatment of atrial fibrillation."
Dr. Shephal Doshi, director of electrophysiology and pacing at St. John's Health Center in Santa Monica, said that, "For most patients, this will change the way we manage them and give them a better quality of life than [warfarin]. They will not have to constantly get their blood levels [of anti-coagulant] checked and will have much more freedom of diet. … We've received more e-mails from patients about these two drugs than about any other therapeutic thing."
Atrial fibrillation is a fluttering of the heart that allows blood to pool in the upper chambers of the heart, where it can form small clots. Those clots can then circulate to the brain, where they cause strokes. An estimated 15% of strokes are caused by atrial fibrillation.
For decades, the only effective treatment for preventing clot formation has been warfarin, which is also known by brand names such as Coumadin and which was originally derived from rat poison. It reduces the risk of stroke by a third to a half, but is a very tricky drug to use. An individual's genetics can alter the amount of drug present in his or her bloodstream, as can the food the individual eats. Vitamin K, in particular — found in salads and other foods — lowers the amount of warfarin in blood.
Too much warfarin in the blood can put a person at risk of life-threatening bleeding. Too little can heighten the risk of stroke. Even in the best clinical trials, only about 70% of patients are able to keep the drug within the desired therapeutic range.
There has thus been "an intense search for alternatives" that could eliminate some of the problems, said Dr. Elaine Hylek of the Boston University School of Medicine.
Pradaxa, known generically as dabigatran, is one such drug. It was approved two weeks ago by the Food and Drug Administration. It is taken twice daily.
Rivaroxaban, developed by Johnson & Johnson and Bayer HealthCare and brand-named Xarelto, will be the second if it is approved by the FDA. Analysts predict that is likely to happen next year.
Dr. Robert M. Califf of the Duke University School of Medicine and his colleagues studied 14,269 atrial fibrillation patients at 1,215 medical centers in 45 countries.
"This was a very high-risk population, with multiple medical problems where a lot of bad stuff could happen," Califf said at a news conference at a Chicago meeting of the American Heart Assn. "They're the patients we most need to protect because they are most vulnerable."
The patients had a median age of 73 and a quarter of them were over 78. They were randomized to receive either rivaroxaban or warfarin.
The study team unlocked the database on Oct. 24, so they have not yet finished analyzing all the data. But if they consider only the patients who completed the study, those taking rivaroxaban had a 21% reduction in risk of stroke, slightly fewer heart attacks and a slightly lower death rate than individuals who received warfarin.
If they consider everyone who entered the study, whether they completed it or not, then stroke and death rates were equivalent in the two groups, meaning that rivaroxaban was at least as good as warfarin. However, there was 40% less bleeding into the brain, and less fatal bleeding with rivaroxaban.
"For the clinician, this is certainly a very positive step forward," Zipes said. "It certainly will facilitate our care of the patients. The big question unanswered, of course, is will it be better than Pradaxa? That awaits further studies."