Dabigatran: AFs gateway drug?

Kaitlyn Dmyterko, senior writer

Genetic variation in metabolism, food and drug interactions, a narrow therapeutic index and the need for frequent international nationalized ratio (INR) checks are just some of the limitations of warfarin, the primary drug used to prevent stroke in patients with atrial fibrillation. Now, there is a new kid on the block, dabigatran (Pradaxa, Boehringer Ingelheim), which may be more cost-effective and safer.

A cost-effectiveness analysis of the RE-LY trial performed by researchers from the Washington University in St. Louis this week found that the 150 mg dose of dabigatran was cost-effective except for when INR control with warfarin was superb.

Approval of the drug stemmed from the results of the RE-LY trial, which enrolled more than 18,000 AF patients with a risk of stroke. Patients administered a 150 mg dose of dabigatran fared better than those who received a 110 mg dose of the drug or warfarin. However, the rates of MI were higher for both doses of dabigatran.

In the current cost-effectiveness analysis, patients administered 150 mg of dabigatran saw the greatest number of quality adjusted life years (QALYs). While dabigatran was most cost-effective for the highest risk patients who had a CHADS₂ score of 3 or more, warfarin was most cost-effective in patients at a moderate risk of stroke.

While the approval of dabigatran is exciting news in the anticoagulant world, will we ever live in a world free of INR checks? Not likely, as least as of right now, Marianne T. Cosentino, APN, MS, of the Yale New Haven Hospital in New Haven, Conn., said during a presentation at this year’s Heart Rhythm Society meeting.

And despite warfarin's shortcomings, Cosentino says the drug  works and has a 62 percent reduction in stroke compared to placebo. However, newer anticoagulants like dabigatran can help resolve warfarin’s limitations and can help patient satisfaction by eliminating the need for anticoagulation monitoring.

But are we out of the woods?

Newer anticoagulants such as rivaroxaban (Xarelto, Bayer Healthcare), apixaban (Xarelto, Bristol-Myers Squibb/Pfizer) and edoxaban (Daiichi Sankyo) are now being investigated in several clinical trials. However, a trial outlining exactly how these newer agents compare with one another is still needed, Jeffrey Weitz, MD, of McMaster University in Hamilton, Ontario, said during this year’s Boston AF Symposium.

It is “difficult to compare apples to oranges,” he said when referring to the efficacy and safety of rivaroxaban and apixaban. Despite these issues, Weitz concluded that “new oral anticoagulants are poised to replace warfarin for stroke prevention in AF … in fact it’s already happening.”

As we move forward in the fight to improve the lives of AF patients by preventing stroke, future studies must outline costs, compliance and bleeding rates of these improved anticoagulants before any will begin to replace warfarin.

What is your position on these newer anticoagulants? Will warfarin one day be sidelined by these novel drugs and INR testing be a thing of the past? The AF market is projected to reach $4.1 billion by 2015, and it will be curious to discover what will the anticoagulant market look like in four years. Let us know your thoughts on this expanding market.

Kaitlyn Dmyterko
Senior writer, Cardiovascular Business
KDmyterko@cardiovascularbusiness.com