Background and aims of the study: Patients with mechanical heart valves are critically dependent upon adequate anticoagulation. The present patients are young, geographically dispersed and socioeconomically deprived. Hospital attendance is erratic, and compliance with conventional anticoagulation difficult. The need exists for an alternative method of anticoagulation that requires neither regular visits nor adjustment of the warfarin dose.
Methods: A five-year prospective randomized double-blind study was undertaken to compare the efficacy and safety of a predetermined, individualized fixed-dose versus adjusted-dose warfarin. Postopoeratively, 296 patients, after an initial dose-finding phase (International Normalized Ratio (INR) 2.0 - 3.5), were randomized to either fixed-dose or adjusted-dose warfarin.
Results: For the intention-to-treat analysis, the groups were well-matched with regard to baseline characteristics. Among patients on fixed-dose warfarin, 63% of INRs were in the range 2.0 - 4.5 compared with 64% in patients on adjusted-dose warfarin. The mean follow up period was 2.4 years in both groups; total follow up was 725 patient-years. There were seven deaths in the fixed-dose warfarin group, and five in the adjusted-dose group (p = 0.52). Thirteen major thrombotic events, occurred in the fixed-dose warfarin group, and four in the adjusted-dose group (p = 0.02). Twelve major hemorrhagic events occurred in each group.
Conclusion: In this predominantly young, impoverished population, despite similar overall INR control, fixed-dose warfarin was associated with an increase in thromboembolic events, but no significant increase in mortality or hemorrhagic events. Fixed-dose warfarin may be an acceptable option where conventional anticoagulation is impracticable. In particular, the study highlighted the difficulties of adequate anticoagulation in a population where compliance is erratic and often non-existent.