In most other respects, dabigatran is a winner so far, Dr. Kowey said. The RE-LY results showed the 150 mg b.i.d. dosage had superior efficacy compared with warfarin, while in ROCKET AF, rivaroxaban proved noninferior but failed to show significant superiority in an intention-to-treat analysis (rivaroxaban showed significant superiority to warfarin in the on-treatment analysis.
"That’s where I get stuck, on the superiority thing," Dr. Kowey said in an interview. "One drug proved itself better than warfarin in a gigantic trial, the other didn’t." Based on what he called the "pristine" RE-LY results, "if you need to pick one of these anticoagulants for your patient it would have to be dabigatran," Dr. Kowey said.
Despite dabigatran’s advantages, he warned physicians against precipitously switching patients who are well controlled on warfarin to dabigatran. "You can’t pull the rug out" from patients. "I hope physicians won’t make that mistake." He noted that some patients maintain a "rock stable" anticoagulated state on warfarin, the drug itself is cheap, and some patients enjoy the social contact they have by regularly returning to their anticoagulation clinic. On the other hand, patients should know that dabigatran is an option, with its superior stroke prevention and reduced cerebral hemorrhage rate compared with warfarin, he said.
Other experts weren’t as sure about dabigatran’s edge over rivaroxaban, citing rivaroxaban’s performance in ROCKET AF in patients with a high comorbidity profile based on their average CHADS score of 3.5. Rivaroxaban’s performance in very sick patients in ROCKET AF was "very impressive," commented Dr. Christine M. Albert, a cardiologist and director of the Center for Arrhythmia Prevention at Brigham and Women’s Hospital in Boston. "We may put a patient on rivaroxaban rather than dabigatran because RE-LY was not done in such a sick population. We’ll probably individualize [use of each drug] based on which patients were studied in each trial," Dr. Albert said in an interview.
Others cited additional considerations needed when prescribing dabigatran, warfarin, and eventually rivaroxaban. "Dabigatran is 80% renally cleared. That will pose problems for some patients, and there is some gastrointestinal bleeding and some dyspepsia with dabigatran," said Dr. Elaine M. Hylek, a cardiologist and warfarin specialist at Boston University. I can’t say that warfarin will disappear. There will be some compelling reasons why warfarin will remain."
A limitation for rivaroxaban is that it is hepatically metabolized, which may pose difficulties or at least require dose adjustment for patients with liver disease who are prescribed rivaroxaban, noted Dr. Gordon F. Tomaselli, professor of medicine and chief of cardiology at Johns Hopkins University in Baltimore.
But availability of dabigatran, and the promise from the ROCKET HF results that rivaroxaban will soon join it on the market, spells the end of warfarin treatment for the vast majority of atrial fibrillation patients, Dr. Tomaselli predicted.
"Over the course of the next year, a lot of my patients will change from warfarin to one of these two [new] drugs," he said in an interview. "What I hear from patients now who are on warfarin is, ‘When can I start with the new drug so that I can stop the rat poison?’"
ROCKET AF was sponsored by Bayer, the company developing rivaroxaban (Xarelto). RE-LY was sponsored by Boehringer-Ingelheim, the company marketing dabigatran (Pradaxa).
Dr. Mahaffey has received consulting fees and research grants from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, Novartis, and Sanofi Aventis. He has also received research grants from Portola, Regado, and The Medicines Company.
Dr. Califf has been a consultant to AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Heart.org, and Kowa research. He received research grants from Amlin and Johnson & Johnson–Scios. Dr. Kowey has been a consultant to Astellas, AstraZeneca, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Blue Ash, Gilead, GlaxoSmithKline, HUYA, Johnson & Johnson, Medtronic, Novartis, Otsuka, Pfizer, Procter & Gamble, Sanofi Aventis, Sequel, Solvay, and St. Jude. He has been a speaker for Sanofi Aventis, he owns stock in Cardionet, and he has received honoraria from GlaxoSmithKline.
Dr. Albert has been a consultant to Novartis, worked on a study sponsored by GlaxoSmithKline, and received research support from St. Jude. Dr. Hylek has served on advisory boards for Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Genentech, Medtronic, Merck, Pfizer, and Sanofi-Aventis. She had received research grants from Bristol-Myers Squibb and Ortho-McNeil. Dr. Tomaselli had no disclosures.