Understanding Differences Among New Oral Anticoagulants Should Increase Compliance

San Francisco, CA—The largest obstacle to market penetration of new oral anticoagulants is patient compliance, said Michael D. Ezekowitz, MD, PhD, of Thomas Jefferson Medical College, Philadelphia, and the Cardiovascular Research Foundation, speaking on Sunday at TCT 2013 about recent trials evaluating the novel agents.

“I kind of duck [the question of penetration] because it’s really impossible to get a number of how many patients there are with atrial fibrillation (AF) and what percentage are being anticoagulated,” he said. “But my sense is that the numbers are much lower than they should be.” Additionally, Ezekowitz estimated that 80% of patients with AF are still being prescribed warfarin, “which is very disappointing,” he said.

The issue of compliance is prevalent with both vitamin K antagonists and novel agents, he explained, adding that this is the major limitation of novel agents, requiring “patient education and cooperation,” Ezekowitz observed. 

But in terms of contraindications for anticoagulation, these “are often in the eye of the beholder,” he said, adding that the same holds true for deciding which novel agent to use on a particular patient because of so many similarities among the drugs.

“All of these agents were synthesized for a particular purpose to obviate the difficulties of using warfarin, so they all have a rapid onset of action and they are all short acting,” Ezekowitz explained. However, dabigatran (Pradaxa, Boehringer Ingelheim) and apixaban (Eliquis, Bristol-Myers Squibb) were evaluated using different dosing schedules than rivaroxiban (Xarelto, Janssen Pharmaceuticals). Additionally, roughly 80% of dabigatran is excreted renally — more than double any of the other agents


Comparing the options

Although not approved in the United States, dabigatran 110 mg achieved noninferiority compared with warfarin in the RE-LY trial with respect to efficacy and safety and a statistically significant reduction in major (P=.003) and any (P<.001) bleeding, Ezekowitz said. “The 150-mg dose exceeded expectations with a 35% reduction in stroke and systemic embolization. It’s the only one of these drugs that shows a reduction in ischemic stroke and that is paralleled by a 74% reduction in intracerebral bleeding but an increase in [gastrointestinal] bleeding,” he explained.

Rivaroxiban evaluated once a day in the ROCKET AF trial was noninferior to warfarin with respect to efficacy and safety but had the same increase in gastrointestinal bleeding as the 150 mg dose of dabigatran (P<.001). Lasting, apixaban, as evaluated in the AVERROES trial, surprised Ezekowitz in that the safety profile was identical to aspirin. The Aristotle trial also showed a reduction in stroke or systemic embolism, all-cause mortality and major bleeding with apixaban vs. warfarin.

“To summarize, dabigatran 150 mg [twice daily] and apixaban 5 mg down-titrated to 2.5 mg [twice daily] were the only two drugs to be superior in efficacy,” he concluded. 


Ezekowitz reports conflicts of interest with several device and pharmaceutical manufacturers. 

Reddy reports grant support from and consulting for Biosense Webster, Boston Scientific, Coherex Medical, GDS, Perseus and St. Jude Medical.