High INR variability and lower time in therapeutic range during warfarin therapy were associated with a higher risk of bleeding (HR 2.15 and HR 2.43, respectively) after mechanical valve implantation.
Cohort (n=4,687)
Yes
Does warfarin treatment quality (TTR, INR variability) and intensity (target INR) affect the risk of thromboembolic events, major bleeding, and death in patients with mechanical heart valve prostheses?
In patients with mechanical heart valves, high warfarin treatment quality (high TTR, low INR variability) improves outcomes, while higher treatment intensity (INR 2.8-3.2 vs 2.2-2.7) increases bleeding and death without added benefit.
Effect estimate: HR 2.15 (95% CI 1.75 to 2.61)
Absolute Event Rate: 4.33% vs 2.08%
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).
Grzymala-Lubanski et al. (2016) conducted a cohort in mechanical heart valve prosthesis (n=4,687). Warfarin vs. High vs low TTR and INR variability; mean INR 2.8-3.2 vs 2.2-2.7 was evaluated on bleeding (high vs low INR variability) (HR 2.15, 95% CI 1.75 to 2.61). High INR variability and lower time in therapeutic range during warfarin therapy were associated with a higher risk of bleeding (HR 2.15 and HR 2.43, respectively) after mechanical valve implantation.
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