Time in therapeutic range and risk of thromboembolism and bleeding in patients with a mechanical heart valve prosthesis

Objective: Oral anticoagulation with vitamin K antagonists is recommended after mechanical heart valve replacement. However, data regarding the association between the quality of vitamin K antagonist treatment and the risk of complications are sparse. Methods: Patients undergoing mechanical heart valve replacement (1997-2012) with available data on international normalized ratio values were identified in Danish registries. The quality of vitamin K antagonist treatment between discharge after valve replacement and 6 months postdischarge (ie, index) was assessed as time in therapeutic range (TTR) ≥70% or <70% reflecting the percentage of time in therapeutic international normalized ratio interval. Patients were followed from index until occurrence of an outcome of interest (ie, thromboembolism and bleeding), death, or end of study (December 31, 2012), whichever came first. The risk of outcomes according to quality of vitamin K antagonist treatment was estimated with multivariable Cox regression. Results: In total, 659 patients undergoing mechanical heart valve replacement were included in the study. Median number of international normalized ratio measurements in the 6-month period after surgery was 13 (interquartile range, 8-19). Median TTR was 54.9% (interquartile range, 39.0%-72.9%) and 29.1% of patients had a TTR ≥70%. Median follow-up was 6.1 years. The risk of thromboembolism was significantly lower in the group with TTR ≥70% compared with TTR <70% (hazard ratio, 0.44; 95% confidence interval, 0.22-0.85), whereas no significant difference concerning risk of bleeding among groups was found (hazard ratio, 0.63; 95% confidence interval 0.36-1.08). Conclusions: In patients undergoing mechanical heart valve replacement, TTR <70% in the 6-month period after surgery was associated with an increased risk of thromboembolic events but not bleeding compared with TTR ≥70%.