New Oral Anticoagulant Options for Stroke Prevention in Atrial Fibrillation

Updated:Feb 18,2013

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New Oral Anticoagulant Options for Stroke Prevention in Atrial Fibrillation = More Opportunities to Improve our Compliance with Evidence-based Care

Disclosure:
Dr. Sila has a modest consultant relationship with Hoffman-LaRoche.
Pub Date: Thursday, Aug. 2, 2012
Author: Cathy Sila, MD
Affiliation: Neurological Institute, University Hospitals - Case Medical Center
                    Case Western Reserve University School of Medicine, Cleveland, Ohio
 
Article Text

Citation:
Furie KL, Goldstein LB, Albers GW, Khatri P, Neyens R, Turakhia MP, Turan TN, Wood KA; on behalf of the American Heart Association Stroke Council, Council on Quality of Care and Outcomes Research, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012: published online before print August 2, 2012, 10.1161/STR.0b013e318266722a.
http://stroke.ahajournals.org/lookup/doi/10.1161/STR.0b013e318266722a 


Atrial fibrillation (AF) is an important cause of stroke and the likely cause of ischemic stroke in 20% of men and 30% of women.1  Cardiac embolism is more likely to result in a major cerebral vessel occlusion, hence the strokes associated with AF more commonly result in severe disability or death.2  Since 1985, thousands of patients with AF have participated in randomized clinical trials demonstrating the efficacy of antithrombotic therapy, most using warfarin, in preventing stroke.3  These data represent the most extensively studied of all stroke subtypes, so much so that they have generated several risk stratification scoring schemes, such as CHA2DS2VASc to further subset the subtype.4  Based on this persuasive data and the potential public health opportunity for the millions of individuals with AF, recommendations for oral anticoagulant therapy in appropriate patients with AF were incorporated into national and international guideline statements and identified as one of the first quality measures for improving stroke care.  Adopted by the AHA/ASA Get with the Guidelines-Stroke initiative in 2001, this quality measure has been endorsed by the Joint Commission in its Primary Stroke Certification, the Centers for Disease Control in its national Coverdell Stroke Registry, the National Quality Foundation, and CMS’ Pay-for Performance and the current Meaningful Use initiatives. 

Although compliance with these guideline recommendations has improved over the past decade, oral anticoagulation remains underused, particularly in the elderly---those at highest risk for stroke.5  The reasons for opting against anticoagulation are numerous and well studied, including documented risk factors for serious bleeding that could negate the beneficial effects of therapy.  However, up to 20% of “unsuitable” patients are so purely by choice and this includes reluctance on the part of the physician as well as the patient.   As “necessity is the mother of invention,” three new oral anticoagulants have emerged offering additional options for patients with AF.  The new AHA/ASA Science Advisory is a welcomed update on the recommendations for the use of oral antithrombotic therapy for the prevention of stroke in patients with non-valvular AF.6

The new oral agents, dabigatran, rivaroxaban, and apixaban, all share desirable properties that specifically address many physicians and patients’ concerns.  All three of the new oral agents have been associated with a reduced risk of serious, life-threatening, fatal, or intracranial bleeding when compared to dose-adjusted warfarin.  Although trial design differed, all three of the agents were efficacious in reducing the primary endpoint of stroke or systemic embolism by demonstrating non-inferiority to warfarin therapy; dabigatran and apixaban were also demonstrated to be superior to warfarin.  The new agents do not require dietary restrictions and have few drug-drug interactions.  They do not “require” regular laboratory monitoring per se, although periodic assessment of renal function is desirable as the drugs’ effect is significantly enhanced in the setting of renal insufficiency.  Based on these data, the new recommendations include warfarin (Class I, Level of Evidence A), dabigatran (Class I, Level of Evidence B), apixaban (Class I, Level of Evidence B), and rivaroxaban (Class IIa, Level of Evidence B) as indicated for the prevention of stroke in patients with non-valvular AF.6-9

Unfortunately, new drugs come at a cost, which despite the cost-effectiveness data still represents additional cost and seems to be the most significant barrier to broader implementation at the present time.  This should provide us important time to become familiar with their usage and answer important questions for patient management.  The lack of regular laboratory monitoring can be viewed as much a downside as a benefit as routine laboratory testing is not yet available for any of the agents.  Specific laboratory testing needs to be developed and made available for emergent assessment of patients with bleeding complications, warranting urgent surgery, and determining eligibility for IV tPA in the event a stroke occurs. In addition, antidotes to reverse the anticoagulant effect for life-threatening or intracranial bleeding need to be developed and tested.10 The rapid onset of activity and shorter duration will challenge patient adherence to therapy but can also reduce the unprotected time during scheduled interruptions of therapy.   In answering patients’ and physicians’ concerns, these new agents offer important advantages in our approach to preventing stroke in patients with AF; time will tell if they will solve the problem of improving compliance with evidence-based care to reduce the risk of death and disability from stroke for our patients.  

References

  1. Roquer J, Campello AR, Gomis M.  Sex differences in first-ever stroke.  Stroke 2003;34:1581-1585.
  2. Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, Singer DE.  Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.  N Engl J Med 2003;349:1019-1026.
  3. Hart RG, Benavente O, McBride R, Pearce LA.  Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.  Ann Intern Med 1999;131:492-501.
  4. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HF.  Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation.  Chest 2010;137:263-272.
  5. Ogilvie IM, Newton N, Weiner SA, Cowell W, Lip GY.  Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010;123:638-645. 
  6. Furie KL, Goldstein LB, Albers GW, Khatri P, Neyens R, Turakhia MP, Turan TN, Wood KA; on behalf of the American Heart Association Stroke Council, Council on Quality of Care and Outcomes Research, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Oral antithrombotic agents for the prevention of stroke in nonvalvular atrial fibrillation: a science advisory for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012: published online before print August 2, 2012, 10.1161/STR.0b013e318266722a.
  7. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener H-C, Joyner CD, Wallentin L.  Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151.
  8. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KA, Califf RM. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891.
  9. Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-992.
  10. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Büller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 2011;124:1573-1579.
-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --
 

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