Effects of low-dose warfarin and aspirin versus no treatment on stroke in a medium-risk patient population with atrial fibrillation.
OBJECTIVE
To assess the optimal stroke prevention treatment for patients with atrial fibrillation (AF) and a low-medium risk (< or =4%) of stroke.


METHODS
A total of 668 patients with persistent or permanent AF, without an indication for full dose and with adequate rate control on sotalol, were randomized to warfarin 1.25 mg + aspirin 75 mg daily (W/A, 334 patients) or no anticoagulation (C, 334 patients). The mean follow-up period was 33 months. The protocol intended to verify a 37% relative risk reduction provided a 4% stroke incidence in the C group.


RESULTS
The stroke incidence was less in the W/A group, although the reduction was not statistically significant (W/A 9.6% versus C 12.3%). Four haemorrhagic strokes were identified, two in each group. Secondary end-points were transient ischaemic attacks (TIA) (W/A 3.3% versus C 4.5%), all cause mortality (W/A 9.3% versus C 10.8%), cardiovascular morbidity (W/A 17.7% versus C 22.2%) and the combination of stroke + TIA (W/A 11.7% versus C 16.5%). Bleedings were documented in 19 versus four patients (W/A 5.7% versus C 1.2%) (P = 0.003), although none fatal. Sinus rhythm (SR) was recorded occasionally in 68 patients (W/A 9.6% versus C 10.8%). The stroke incidence tended to be higher in those with SR than without, 16.2% versus 10.4%.


CONCLUSIONS
Our results were inconclusive, but consistent with a small beneficial effect of W/A for reduction of stroke and major vascular events in AF patients at moderate risk. The low-dose regiment produced, however, a significantly increased risk of bleedings. Documented SR occasionally recorded may represent a subpopulation that warrants full dose warfarin.
Edvardsson
N
N
Division of Cardiology, Sahlgrenska University Hospital, Stockholm, Sweden.
Juul-Möller
S
S
Omblus
R
R
Pehrsson
K
K
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects; D028761:Withholding Treatment
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D001241:Aspirin