TY - JOUR
T1 - Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation
AU - Hansen, Morten L
AU - Sørensen, Rikke
AU - Clausen, Mette T
AU - Fog-Petersen, Marie Louise
AU - Raunsø, Jakob
AU - Gadsbøll, Niels
AU - Gislason, Gunnar H
AU - Folke, Fredrik
AU - Andersen, Søren
AU - Schramm, Tina K
AU - Abildstrøm, Steen Z
AU - Poulsen, Henrik E
AU - Køber, Lars
AU - Torp-Pedersen, Christian
PY - 2010/9/13
Y1 - 2010/9/13
N2 - Background: Patients with atrial fibrillation (AF) often require anticoagulation and platelet inhibition, but data are limited on the bleeding risk of combination therapy. Methods: We performed a cohort study using nationwide registries to identify all Danish patients surviving first-time hospitalization for AF between January 1, 1997, and December 31, 2006, and their posthospital therapy of warfarin, aspirin, clopidogrel, and combinations of these drugs. Cox proportional hazards models were used to estimate risks of nonfatal and fatal bleeding. Results: A total of 82 854 of 118 606 patients (69.9%) surviving AF hospitalization had at least 1 prescription filled for warfarin, aspirin, or clopidogrel after discharge. During mean (SD) follow-up of 3.3 (2.6) years, 13 573 patients (11.4%) experienced a nonfatal or fatal bleeding. The crude incidence rate for bleeding was highest for dual clopidogrel and warfarin therapy (13.9% per patient-year) and triple therapy (15.7% per patient-year). Using warfarin monotherapy as a reference, the hazard ratio (95% confidence interval) for the combined end point was 0.93 (0.88-0.98) for aspirin, 1.06 (0.87-1.29) for clopidogrel, 1.66 (1.34-2.04) for aspirin-clopidogrel, 1.83 (1.72-1.96) for warfarin-aspirin, 3.08 (2.32-3.91) for warfarin-clopidogrel, and 3.70 (2.89-4.76) for warfarin-aspirin-clopidogrel. Conclusions: In patients with AF, all combinations of warfarin, aspirin, and clopidogrel are associated with increased risk of nonfatal and fatal bleeding. Dual warfarin and clopidogrel therapy and triple therapy carried a more than 3-fold higher risk than did warfarin monotherapy.
AB - Background: Patients with atrial fibrillation (AF) often require anticoagulation and platelet inhibition, but data are limited on the bleeding risk of combination therapy. Methods: We performed a cohort study using nationwide registries to identify all Danish patients surviving first-time hospitalization for AF between January 1, 1997, and December 31, 2006, and their posthospital therapy of warfarin, aspirin, clopidogrel, and combinations of these drugs. Cox proportional hazards models were used to estimate risks of nonfatal and fatal bleeding. Results: A total of 82 854 of 118 606 patients (69.9%) surviving AF hospitalization had at least 1 prescription filled for warfarin, aspirin, or clopidogrel after discharge. During mean (SD) follow-up of 3.3 (2.6) years, 13 573 patients (11.4%) experienced a nonfatal or fatal bleeding. The crude incidence rate for bleeding was highest for dual clopidogrel and warfarin therapy (13.9% per patient-year) and triple therapy (15.7% per patient-year). Using warfarin monotherapy as a reference, the hazard ratio (95% confidence interval) for the combined end point was 0.93 (0.88-0.98) for aspirin, 1.06 (0.87-1.29) for clopidogrel, 1.66 (1.34-2.04) for aspirin-clopidogrel, 1.83 (1.72-1.96) for warfarin-aspirin, 3.08 (2.32-3.91) for warfarin-clopidogrel, and 3.70 (2.89-4.76) for warfarin-aspirin-clopidogrel. Conclusions: In patients with AF, all combinations of warfarin, aspirin, and clopidogrel are associated with increased risk of nonfatal and fatal bleeding. Dual warfarin and clopidogrel therapy and triple therapy carried a more than 3-fold higher risk than did warfarin monotherapy.
U2 - 10.1001/archinternmed.2010.271
DO - 10.1001/archinternmed.2010.271
M3 - Journal article
SN - 2168-6106
VL - 170
SP - 1433
EP - 1441
JO - JAMA Internal Medicine
JF - JAMA Internal Medicine
IS - 16
ER -