Although the rate of bleeding among patients with atrial fibrillation (AF) taking novel oral anticoagulants in randomized controlled trials is described, the rate of bleeding with “real-world” use is uncertain.
Methods:
We conducted a retrospective electronic medical record interrogation and subsequent chart review among patients within Intermountain Healthcare between October 2010 and November 2012. Patients were included if they had a diagnosis of AF and were receiving either dabigatran or rivaroxaban. Rates of major bleeding were calculated.
Results:
Among 2579 patients, 13 (0.5%) experienced major bleeding (95% confidence interval [CI] 0.23-0.77), 5 (0.19%) experienced intracranial hemorrhage (95% CI 0.02-0.36), and 2 (0.08%) experienced fatal bleeding. Of the 13 patients experiencing a major bleed, 8 (61.5%) would have been excluded from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) clinical trials.
Conclusion:
We observed a rate of major bleeding similar to that reported in randomized clinical trials among patients with AF prescribed dabigatran or rivaroxaban.
GoASHylekEMPhillipsKA. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285(18):2370–2375.
2.
YouJJSingerDEHowardPA. Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2 suppl):e531S–e575S.
3.
WannLSCurtisABJanuaryCT. 2011ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;57(2):223–242.
4.
European HeartRhythmA, European Association for Cardio-ThoracicSCammAJ. Guidelines for the management of atrial fibrillation: the task force for the management of atrial fibrillation of the European society of cardiology (ESC). Europace. 2010;12(10):1360–1420.
5.
SnowVWeissKBLeFevreM. Management of newly detected atrial fibrillation: a clinical practice guideline from the American academy of family physicians and the American college of physicians. Ann Intern Med. 2003;139(12):1009–1017.
6.
ConnollySJEzekowitzMDYusufS. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–1151.
7.
PatelMRMahaffeyKWGargJ. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–891.
8.
SchulmanSKearonC, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3(4):692–694.
9.
SouthworthMRReichmanMEUngerEF. Dabigatran and postmarketing reports of bleeding. N Engl J Med. 2013;368(14):1272–1274.
10.
LipGYFrisonLHalperinJLLaneDA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol. 2011;57(2):173–180.
11.
PistersRLaneDANieuwlaatRde VosCBCrijnsHJLipGY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro heart survey. Chest. 2010;138(5):1093–1100.
12.
LarsenTBRasmussenLHSkjøthF. 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.
13.
GrangerCBAlexanderJHMcMurrayJJ. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–992.
14.
GageBFWatermanADShannonWBoechlerMRichMWRadfordMJ. Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. JAMA. 2001;285(22):2854–2870.
15.
LopesRDAl-KhatibSMWallentinL. Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial. Lancet. 2012;380(9855):1749–1758. doi: 10.1016/S0140-6736(12)60986-6.
16.
GuoYLipGYApostolakisS. Bleeding risk assessment in patients with atrial fibrillation who are taking oral anticoagulants. Hosp Pract (1995). 2013;41(1):71–78. doi: 10.3810/hp.2013.02.1012.
17.
WannLSCurtisAB, Ellenbogen KA, et al. 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (update on dabigatran): a report of the American college of cardiology foundation/American heart association task force on practice guidelines. J Am Coll Cardiol. 2011;57(11):1330–1337.
18.
CairnsJAConnollySMcMurtrySStephensonMTalajicM, CCS Atrial Fibrillation Guidelines Committee. Canadian cardiovascular society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol. 2011;27(1):74–90.
19.
CammAJLipGY, De Caterina R, et al. 2012 Focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation: developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–2747.
20.
SkanesACHealeyJSCairnsJA. Focused 2012 update of the Canadian cardiovascular society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol. 2012;28(2):125–136.
21.
JanuaryCTWannLSAlpertJS. 2014AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: executive summary [published online March 28, 2014.]. J Am Coll Cardiol. 2014. doi: 10.1016/j.jacc.2014.03.021.
