Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study

TY - JOUR

T1 - Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy

T2 - a nationwide cohort study

AU - Lamberts, Morten

AU - Lip, Gregory Y H

AU - Hansen, Morten Lock

AU - Lindhardsen, Jesper

AU - Olesen, Jonas Bjerring

AU - Raunsø, Jakob

AU - Olsen, Anne-Marie Schjerning

AU - Andersen, Per Kragh

AU - Gerds, Thomas Alexander

AU - Fosbøl, Emil Loldrup

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

PY - 2014/11/18

Y1 - 2014/11/18

N2 - Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.Objective: To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.Design: Observational cohort study.Setting: Nationwide registries. Patients: Danish patients with AF hospitalized between 1997 and 2011.Measurements: Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.Results: Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding. Limitation: Observational design and unmeasured confounders.Conclusion: Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.

AB - Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.Objective: To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.Design: Observational cohort study.Setting: Nationwide registries. Patients: Danish patients with AF hospitalized between 1997 and 2011.Measurements: Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.Results: Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding. Limitation: Observational design and unmeasured confounders.Conclusion: Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.

U2 - 10.7326/M13-1581

DO - 10.7326/M13-1581

M3 - Journal article

C2 - 25402512

SN - 0003-4819

VL - 161

SP - 690

EP - 698

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

IS - 10

ER -