Relationship between the Occurrence of Thromboembolism and INR Measurement Interval in Low Intensity Anticoagulation after Aortic Mechanical Valve Replacement

Background: We investigated changes in the International Normalized Ratio (INR) and its measurement interval in patients with thromboembolic events who were treated by low intensity anticoagulation therapy after isolated mechanical aortic valve replacement. Materials and Methods: Seventy-seven patients who underwent surgery from June 1990 to September 2006 were enrolled in the study and observed until August 2008. The patients were followed up at 4~8 week intervals and their warfarin (Coumadin)$^{(R)}$ dosage was adjusted aiming for a target range of INR 1.5~2.5. The rate of thromboembolic events was obtained. Changes in the mean INR and INR measurement interval were comparatively analyzed between the normal group (event free group, N=52) who had no anticoagulation-related complications and the thromboembolic group (N=10). Hospital records were reviewed retrospectively. Results: The observation period was 666.75 patient-years. Thromboembolic events occurred in 10 patients. The linearized occurrence rate of thromboembolism was 1.50%/patient-years. Actuarial thromboembolism-free rates were $97.10{\pm}2.02%$ at 5 years, $84.30{\pm}5.22%$ at 10 years, and $67.44{\pm}12.14%$ at 15 years. The percentages of INR within the target range and mean INR were not statistically significantly different for the normal and thromboembolic groups. However, the mean INR during the segmented period just before the events showed a significantly lower level in the thromboembolic group (during a 4 month period: normal group, $1.86{\pm}0.14$ vs. thromboembolic group, $1.50{\pm}0.28$, p<0.001). The mean intervals of INR measurement during the whole observation period showed no significant differences between groups, but in the segmented period just before the events, the interval was significantly longer in thromboembolic group (during a 6 month period: normal group, $49.04{\pm}9.47$ days vs. thromboembolic group, $65.89{\pm}44.88$ days, p<0.01). Conclusion: To prevent the occurrence of thromboembolic events in patients who receive isolated aortic valve replacement and low intensity anticoagulation therapy, we suggest that it would be safe to maintain an INR level above 1.8 and to measure the INR at least every 7~8 weeks.