Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial fibrillation investigators.
OBJECTIVE
Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation.


METHODS
This is an analysis of the Atrial Fibrillation Investigators database, which contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure. Outcomes included ischemic stroke, serious bleeding (intracranial hemorrhage or systemic bleeding requiring hospitalization, transfusion, or surgery), and cardiovascular events (ischemic stroke, myocardial infarction, systemic embolism, or vascular death).


RESULTS
The analysis included 8932 patients and 17 685 years of observation from 12 trials. Patient age increased risk of ischemic stroke (adjusted hazard ratio per decade increase 1.45; 95% CI, 1.26 to 1.66), serious bleeding (1.61; 1.47 to 1.77), and cardiovascular events (1.43; 1.33 to 1.53). Compared with placebo, OAC and AP significantly reduced the risk of ischemic stroke (OAC, 0.36; 0.29 to 0.45; AP, 0.81; 0.72 to 0.90) and cardiovascular outcomes (OAC, 0.59; 0.52 to 0.66; AP, 0.81; 0.75 to 0.88), whereas OAC increased risk of serious bleeding (1.56; 1.03 to 2.37). The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome. Compared with placebo, the relative benefit of AP for preventing ischemic stroke decreased significantly as patients aged (P=0.01).


CONCLUSIONS
As patients with atrial fibrillation age, the relative efficacy of AP to prevent ischemic stroke appears to decrease, whereas it does not change for OAC. Because stroke risk increases with age, the absolute benefit of OAC increases as patients get older.
van Walraven
Carl
C
University of Ottawa and Ottawa Health Research Institute Canada, Ottawa, Canada. carlv@ohri.ca
Hart
Robert G
RG
Connolly
Stuart
S
Austin
Peter C
PC
Mant
Jonathan
J
Hobbs
F D Richard
FD
Koudstaal
Peter J
PJ
Petersen
Palle
P
Perez-Gomez
Francisco
F
Knottnerus
J Andre
JA
Boode
Beppie
B
Ezekowitz
Michael D
MD
Singer
Daniel E
DE
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000453:epidemiology*; D002545:Brain Ischemia / Q000453:epidemiology / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000517:prevention & control; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000517:prevention & control*; D013927:Thrombosis / Q000188:drug therapy / Q000453:epidemiology* / Q000517:prevention & control*
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors