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Dabigatran and Myocardial InfarctionDabigatran and Myocardial Infarction FREE TO VIEW

Stefan H. Hohnloser, MD; Gregory Y. H. Lip, MD
Author and Funding Information

From the Department of Cardiology (Dr Hohnloser), J. W. Goethe University; and Haemostasis, Thrombosis and Vascular Biology Unit (Dr Lip), Birmingham City Hospital.

CORRESPONDENCE TO: Stefan H. Hohnloser, MD, Department of Cardiology, J. W. Goethe University, Theodor-Stern-Kaie 7, 60590 Frankfurt, Germany; e-mail: hohnloser@em.uni-frankfurt.de


FINANCIAL/NONFINANCIAL DISCLOSURES: The authors have reported to CHEST the following conflicts of interest: Dr Hohnloser has been a consultant and advisor to Bayer HealthCare AG; Boehringer Ingelheim GmbH; Bristol-Myers Squibb Company; Pfizer, Inc; Johnson & Johnson Services, Inc; sanofi-aventis; Gilead; and Les Laboratoires Servier and has participated in speaker activities for Bayer HealthCare AG; Boehringer Ingelheim GmbH; Bristol-Myers Squibb Company; Pfizer, Inc; Johnson & Johnson Services, Inc; and sanofi-aventis. Dr Lip has served as a consultant for Bayer HealthCare AG; Astellas Pharma Inc, Merck Sharp & Dohme Corp, Sanofi SA, Bristol-Myers Squibb Company/Pfizer, Inc; Daiichi Sankyo Company, Limited; Biotronik SE & Co.KG, Medtronic, Inc; Portola Pharmaceuticals, Inc; and Boehringer Ingelheim GmbH and has been on the speakers bureau for Bayer HealthCare AG; Bristol-Myers Squibb Company/Pfizer, Inc; Boehringer Ingelheim GmbH; Daiichi Sankyo Company, Limited; and Medtronic, Inc.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(2):e70-e71. doi:10.1378/chest.14-2534
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Published online
To the Editor:

In a recent issue of CHEST (January 2015), Davidson1 commented on the association between direct thrombin inhibitors, including bivalirudin, ximelagatran, and dabigatran, and cardiac thrombosis. He concludes that the guilt [of these substances in causing cardiac thrombosis] appears undeniable and that clinicians should avoid prescribing direct thrombin inhibitors. This statement is based on a rather one-sided thought process and warrants a more balanced view based on a careful review of the current knowledge, particularly with respect to the use of dabigatran. The major indication for this drug is stroke prevention in atrial fibrillation (AF) for which it has been approved since 2009. Hence, our response focuses on dabigatran in patients with AF.

In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial, there were numerically more myocardial infarctions (MIs) in patients taking dabigatran (0.8%/y) than in those taking warfarin (0.6%/y), but this finding was nonsignificant. The absolute difference in rates of new MIs was extremely low (0.2%/y), limiting statistical power for any comparison. In a post hoc analysis of the RE-LY trial, a variety of other ischemia-related outcomes were similar between treatment groups.2 An estimation of the net clinical benefit indicated a significant difference in favor of dabigatran.

Several real-world datasets have been published evaluating the benefits and risks of dabigatran. In a nationwide Danish registry study, 4,978 incident dabigatran users were propensity matched to 8,936 users of warfarin.3 Rates for stroke, peripheral embolism, and major bleeding were similar for dabigatran and warfarin. However, mortality, intracranial bleeding, and MI events were lower with dabigatran. The unadjusted hazard ratio (HR) for MI for dabigatran 110 mg bid vs warfarin was 0.60 (95% CI, 0.33-1.02) and for dabigatran 150 mg bid vs warfarin, 0.62 (95% CI, 0.30-1.14). The largest study on dabigatran 150 mg was published by the US Food and Drug Administration,4 which collected data from > 134,000 Medicare patients treated with dabigatran for stroke prevention in AF. Dabigatran compared with warfarin significantly reduced the risk of stroke (HR, 0.80; 95% CI, 0.67-0.96), intracranial bleeding (HR, 0.34; 95% CI, 0.26-0.46), and mortality (HR, 0.86; 95% CI, 0.77-0.96). Of particular note, there were numerically fewer MIs in patients taking dabigatran than in those taking warfarin (HR, 0.92; 95% CI, 0.78-1.08).

Warfarin offers good protection against cardiac events. In recent thromboprophylaxis trials with oral factor Xa inhibitors (eg, rivaroxaban, edoxaban) compared with well-managed warfarin (as reviewed in a recent European consensus document5), numerically higher MI rates were actually seen with oral factor Xa inhibitors compared with warfarin.

Thus, the commentary by Davidson1 needs to be put into perspective. Absolute MI rates are small and nonsignificant and may reflect better cardioprotection with warfarin rather than an adverse effect of direct thrombin inhibitors or oral factor Xa inhibitors.

References

Davidson BL. The association of direct thrombin inhibitor anticoagulants with cardiac thrombosis. Chest. 2015;147(1):21-24. [CrossRef] [PubMed]
 
Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012;125(5):669-676. [CrossRef] [PubMed]
 
Larsen TB, Rasmussen LH, Skjøth F, et al. Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol. 2013;61(22):2264-2273. [CrossRef] [PubMed]
 
Graham DJ, Reichman ME, Wernecke M, et al. Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for non-valvular atrial fibrillation [published online ahead of print October 30, 2014]. Circulation. doi:10.1161/CIRCULATIONAHA.114.012061.
 
Lip GYH, Windecker S, Huber K, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS) [published online ahead of print August 25, 2014]. Eur Heart J. doi:10.1093/eurheartj/ehu298.
 

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References

Davidson BL. The association of direct thrombin inhibitor anticoagulants with cardiac thrombosis. Chest. 2015;147(1):21-24. [CrossRef] [PubMed]
 
Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial. Circulation. 2012;125(5):669-676. [CrossRef] [PubMed]
 
Larsen TB, Rasmussen LH, Skjøth F, et al. Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol. 2013;61(22):2264-2273. [CrossRef] [PubMed]
 
Graham DJ, Reichman ME, Wernecke M, et al. Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for non-valvular atrial fibrillation [published online ahead of print October 30, 2014]. Circulation. doi:10.1161/CIRCULATIONAHA.114.012061.
 
Lip GYH, Windecker S, Huber K, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS) [published online ahead of print August 25, 2014]. Eur Heart J. doi:10.1093/eurheartj/ehu298.
 
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