Trial of different intensities of anticoagulation in patients with prosthetic heart valves

We compared the efficacy and complications of anticoagulation with warfarin in 258 patients with prosthetic heart valves treated with regimens of "moderate intensity" (prothrombin-time ratio, 1.5; international normalized ratio, 2.65) or "high intensity" (prothrombin-time ratio, 2.5; international normalized ratio, 9) in a prospective, randomized study. The two patient groups were followed up for 421 patient-years and 436 patient-years, respectively. Eleven patients were lost to follow-up. Thromboembolism occurred with similar frequency in the two groups (4.0 and 3.7 episodes per 100 patient-years, respectively), but there was a total of 6.2 bleeding episodes per 100 patient-years in the moderate-intensity group, as compared with 12.1 episodes in the high-intensity group (P less than 0.002). There were 5.2 episodes of minor bleeding per 100 patient-years in the moderate-intensity group, as compared with 10.1 episodes in the high-intensity group (P less than 0.01). Major bleeding was also more common in the high-intensity group (2.1 episodes per 100 patient-years--including the only two fatal hemorrhages--as compared with 0.95 episode in the moderate-intensity group), but the difference was not statistically significant. We conclude that a moderate anticoagulant effect (prothrombin-time ratio, about 1.5) in patients with a mechanical prosthetic heart valve offers protection equivalent to that of more intensive therapy, but at a significantly lower risk.