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


METHODS
Observational cohort study.


METHODS
Nationwide registries.


METHODS
Danish patients with AF hospitalized between 1997 and 2011.


METHODS
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.


CONCLUSIONS
Observational design and unmeasured confounders.


CONCLUSIONS
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.


BACKGROUND
None.
Morten
M
Lamberts
Gregory Y H
GY
Lip
Morten Lock
ML
Hansen
Jesper
J
Lindhardsen
Jonas Bjerring
JB
Olesen
Jakob
J
Raunsø
Anne-Marie Schjerning
AM
Olsen
Per Kragh
PK
Andersen
Thomas Alexander
TA
Gerds
Emil L
EL
Fosbøl
Christian
C
Torp-Pedersen
Gunnar H
GH
Gislason
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004347:Drug Interactions; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D013923:Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005343:Fibrinolytic Agents