Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study

Abstract

Aim: To evaluate whether long-term treatment with a fixed low dose of warfarin in combination with aspirin improves the prognosis compared with aspirin treatment alone after an acute myocardial infarction (AMI).

Methods: Patients who were hospitalized for AMI were randomized to either 1.25mg of warfarin plus 75mg of aspirin (n=1659) daily or 75mg of aspirin alone (n=1641). The study was performed according to the PROBE (Prospective Open Treatment and Blinded End Point Evaluation) design and was conducted at 31 hospitals in Sweden. The median follow-up time was 5.0 years. In the aspirin+warfarin group, 30.2% were permanently withdrawn as opposed to 14.0% in the aspirin group (P<0.0001). Analyses were performed on an intention-to-treat basis.

Results: The combination of cardiovascular death, reinfarction or stroke was registered in 28.1% in the aspirin+warfarin group versus 28.8% in the aspirin group (NS). Cardiovascular deaths occurred in 14.2% in the aspirin+warfarin group vs 15.7% in the aspirin group (NS). Whereas no difference was found with regard to total mortality or reinfarction, those randomized to aspirin+warfarin had a reduced occurrence of stroke (4.7% vs 7.1%; P=0.004). The percentage of patients who suffered a serious bleed was 1.0% in the aspirin group vs 2.2% in the combination group (P=0.0006).

Conclusion: A fixed low dose of warfarin added to aspirin in the long term after AMI did not reduce the combined risk of cardiovascular death, reinfarction or stroke. The results did, however, indicate that a fixed low dose of warfarin added to aspirin reduced the risk of stroke, but this was a secondary end point. The combination of aspirin and warfarin was associated with an increased risk of bleeding.