Warfarin treatment quality and prognosis in patients with mechanical heart valve prosthesis

Objectives To study the impact of time in therapeutic range (TTR) and international normalised ratio (INR) variability on the risk of thromboembolic events, major bleeding complications and death after mechanical heart valve (MHV) implantation. Additionally, the importance of different target INR levels was elucidated. Methods A retrospective, non-randomised multicentre cohort study including all patients with mechanical heart valve (MVH) prosthesis registered in the Swedish National Quality Registry Auricula from 2006 to 2011. Data were merged with the Swedish National Patient Registry, SWEDEHEART and Cause of Death Registry. Results In total 4687 ordination periods, corresponding to 18 022 patient-years on warfarin, were included. High INR variability (above mean ≥0.40) or lower TTR (≤70%) was associated with a higher risk of bleeding (rate per 100 years 4.33 (95% CI 3.87 to 4.82) vs 2.08 (1.78 to 2.41); HR 2.15 (1.75 to 2.61) and 5.13 (4.51 to 5.82) vs 2.30 (2.03 to 2.60); HR 2.43 (2.02 to 2.89)), respectively. High variability and low TTR combined was associated with an even higher risk of bleedings (rate per 100 years 4.12 (95% CI 3.68 to 4.51) vs 2.02 (1.71 to 2.30); HR 2.16 (1.71 to 2.58) and 4.99 (4.38 to 5.52) vs 2.36 (2.06 to 2.60); HR 2.38 (2.05 to 2.85)) compared with the best group. Higher treatment intensity (mean INR 2.8-3.2 vs 2.2-2.7) was associated with higher rate of bleedings (2.92 (2.39 to 3.47) vs 2.48 (2.21 to 2.77); HR 1.29 (1.06 to 1.58)), death (3.36 (2.79 to 4.02) vs 1.89 (1.64 to 2.17), HR 1.65 (1.31 to 2.06)) and complications in total (6.61 (5.74 to 7.46) vs 5.65 (5.20 to 6.06); HR 1.24 (1.06 to 1.41)) after adjustment for MHV position, age and comorbidity. Conclusions A high warfarin treatment quality improves outcome after MHV implantation, both measured with TTR and INR variability. No benefit was found with higher treatment intensity (mean INR 2.8- 3.2 vs 2.2-2.7)