New Agents Get Second Opinion for First Line Use
By: Alere Staff
The approval of Pradaxa® medication (dabignatran) in October 2010 opened the door to new choices of anticoagulants for physicians and their patients. Since then, a second alternative, Xarelto® anticoagulant medication (rivaroxaban) has entered the market in hopes of replacing warfarin. News and investment in pharmaceutical R&D has been slow, so the time was right for headlines and press releases heralding their arrival.
Warfarin remains the gold standard for prophylactic stroke prevention with over 50 years of patient use. Warfarin’s first real competition has arrived and with it, big pharmaceutical marketing. On track to become the medical news topic of the decade, new drugs called non-vitamin K antagonists are creating a buzz exceeding medical marketing communication company budgets.
New agents are an alternative to warfarin to prevent dangerous blood clot development. The news is welcome for physician’s who find it difficult to manage warfarin. The uptake however has been slow with warfarin retaining over 80% market share through 2011 despite organizations such as the American Heart Association (AHA) and American College of Chest Physician’s support of their use as first line agents.1 Slowing the adoption of Pradaxa has been news from countries that reimburse for the drug cost. Australia, Japan and the European Medicines Agency have issued warnings over its use. In the U.S., Pradaxa related FDA reported adverse events totaled 817 compared to warfarin’s 490 in 2011.2
Warfarin, commonly known as ‘the drug doctor’s love to hate’, has had little support since 2010. Meanwhile, marketed as convenient, easy-to-use and without the need to monitoring, new agents lack of drug and dietary interactions make them seem like an ideal overnight replacement for warfarin. Alas, this is not happening. The reason lies in the difficulty of balancing safe and effective anticoagulation.
A counter position to the new agents was published in the August 2012 edition of AHA’s peer-review journal Circulation. The article, New oral anticoagulants should not be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation identifies 8 areas where new agents do not provide an advantage over well managed warfarin.
Disadvantages of New Oral Anticoagulants3
- Short half-life
- No routine coagulation monitoring required
- No coagulation assay easily available to precisely measure their anticoagulant effect
- Cannot titrate dose
- Cannot assess causes of failure of therapy (poor adherence)
- Cannot assess degree of coagulation inhibition for urgent situations
- No anecdote or reversal
- High cost
Many of the same attributes that make the new agents clinically attractive are also their greatest problems, commented Ansell. Additionally, when warfarin is managed, the advantages of the new agent’s “vanish”. Earlier studies by Gage and Shah have found warfarin to actually be more cost-effective when the time in therapeutic range can meet or exceed 73%.4,5 Clinician’s challenge in adopting new agents over warfarin was initially identified during the 2010 AHA international meeting and reinforced by Ansell, a bad warfarin patient will make a worse new agent patient.
While new agents are more focused on a specific areas of inhibition in patient’s natural clotting cascade than warfarin, Ansell feels there are far too many ‘unknowns’ for new agents to automatically replace warfarin. Instead, Ansell supports home INR testing through patient self-testing.3 Dr. Ansell is the lead author of the pending publishing STABLE study where warfarin was found to be optimally managed through weekly patient self-testing.6
- Kirley, L . (2012). National Trends in Oral Anticoagulant Use in the United States, 2007 to 2011. Circulation: Cardiovascular Quality Outcomes. 5,00-00.
- QuarterWatch, Monitoring FDA MedWatch Reports. (2011). Anticoagulants the Leading Reported Drug Risk in 2011. Institute for Safe Medication Practices, 4th Quarter.
- Ansell, J. (2012). New oral anticoagulants should not be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation. Circulation, 125:165-170.
- Hooman Kamel, MD. 2012. Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Patients With Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack.Stroke; 43:881-883.
- Shah, Shimoli V. MD. 2011. Cost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation.Circulation; 123:2562-2570.
- DeSantis G, Hogan-Schlientz J, Liska G, Kipp S, Sallee R, Wurster M, Ansell J. Real-world warfarin patients achieve and maintain high time in target range, showing suitability for patient self-testing across all age groups [abstract]. American Journal of Hematology. 2012;87(suppl 1):S149.