D-dimer to guide the intensity of anticoagulation in Chinese patients after mechanical heart valve replacement: a randomized controlled trial

Abstract

Essentials Low anticoagulation intensity reduces bleeding but increases thrombosis during warfarin therapy. Elevated D-dimer level is associated with increased thrombosis events. D-dimer can be used to find potential thrombosis in those receiving low intensity therapy. D-dimer-guided therapy may be the optimal strategy for those with mechanical heart valve replacement. Summary: Background Controversies remain regarding the optimal anticoagulation intensity for Chinese patients after mechanical heart valve replacement despite guidelines having recommended a standard anticoagulation intensity. Objectives To investigate whether D-dimer could be used to determine the optimal anticoagulation intensity in Chinese patients after mechanical heart valve replacement. Patients/Methods This was a prospective, randomized controlled clinical study. A total of 748 patients following mechanical heart valve replacement in Wuhan Asia Heart Hospital were randomized to three groups at a ratio of 1 : 1 : 1. Patients in two control groups received warfarin therapy based on constant standard intensity (international normalized ratio [INR], 2.5–3.5; n = 250) and low intensity (INR, 1.8–2.6; n = 248), respectively. In the experimental group (n = 250), warfarin therapy was initiated at low intensity, then those with elevated D-dimer levels were adjusted to standard intensity. All patients were followed-up for 24 months until the occurrence of endpoints, including bleeding events, thrombotic events and all-cause mortality. Results A total of 718 patients were included in the analysis. Fifty-three events occurred during follow-up. There was less hemorrhage (3/240 vs. 16/241; hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.07–0.45) and all-cause mortality (4/240 vs. 12/241; HR, 0.33; 95% CI, 0.12–0.87) observed in the D-dimer-guided group than in the standard-intensity group. A lower incidence of thrombotic events was also observed in the D-dimer-guided group when compared with the low-intensity group (5/240 vs. 14/237; HR, 0.35; 95% CI, 0.14–0.85). Overall, the total events were less in the D-dimer-guided group (9/240) when compared with the other two control groups (24/241, 20/237; HR, 0.37, 0.44; 95% CI, 0.19–0.72, 0.21–0.90. Conclusions The D-dimer-guided adjustment of anticoagulation intensity could reduce adverse events in Chinese patients after mechanical heart valve replacement. Trial Registry: NCT01996657; ClinicalTrials.gov.