VARIABILITY IN ANTICOAGULATION CONTROL PREDICTS THROMBOEMBOLISM AFTERMECHANICAL CARDIAC-VALVE REPLACEMENT - A 23-YEAR POPULATION-BASED STUDY

Objective: To assess optimal control of blood anticoagulation to maxim ize antithrombotic protection after mechanical cardiac valve replaceme nt, Design: A population-based study of 96 patients with a mean follow -up of 7.7 years (range, 1 month to 23 years) was performed in Olmsted County, Minnesota, and 10,301 prothrombin time (PT) ratios were deter mined after mechanical heart valve replacement, Material and Methods: PT ratios were analyzed in a new time-dependent Cox proportional-hazar ds model by defining an algorithm for comparing variability in PT rati os at each month of follow-up and relating these to thromboembolic eve nts, The new method was compared with several conventional time-indepe ndent definitions, Results: During 740 person-years of follow-up, 19 o f 96 patients (20%) had 27 thromboembolic events, Of these 19 patients , 8 (42%) had events within 3 months after valve replacement, Freedom from any thromboembolic event was 72% at 15 years, The event rate was high (7.5 % per year) during high variability and low (0.9% per year) during low variability in the PT ratio, This relationship was lost whe n time dependence was removed, More PT ratios were less than 1.5 durin g high (27%) than during low (19%) variability, Several conventional d efinitions of adequacy of anticoagulation that averaged PT ratios befo re a thromboembolic event or throughout follow-up or that compared the proportion of PT ratios above or below a fixed ratio did not define o r only partially defined different thromboembolic risks, Conclusion: P eriods of high and low variability of PT ratios define high and low ri sk of thromboembolism, respectively.