Treatment of acute pulmonary embolism after catheter-directed thrombolysis with dabigatran versus warfarin: results of a multicenter randomized "RE-SPIRE" trial.

BACKGROUND: Thrombolytic therapy is effective method in the high-risk acute pulmonary embolism treatment (PE). Reduced-dose thrombolysis (RDT) plus oral anticoagulation therapy is effective and safe method in the moderate and severe PE treatment. It is leading to good early and intermediate-term outcomes. In the RE-COVER and RE-COVER II studies, dabigatran shown similar effectiveness as warfarin in the acute PE treatment.

HYPOTHESIS: Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the PE prevention after mechanical fragmentation and reduced-dose thrombolysis (CDT+RDT) in patients with high and intermediate-high PE risk.

PURPOSE: To evaluate the efficacy and safety (incidence of clinically significant recurrence of venous thromboembolic complications and deaths) during a 6-month course of treatment with dabigatran or warfarin in patients with high- and intermediate-high acute PE risk after endovascular mechanical thrombus fragmentation procedure with reduced-dose thrombolysis (CDT+RDT).

MATERIALS AND METHODS: The "RE-SPIRE" is a prospective, multicenter randomized double-arm study. Over a 5-year period, 66 consecutive patients with symptomatic high- and intermediate-high PE risk after endovascular mechanical thrombus fragmentation procedure with reduced-dose thrombolysis (CDT+RDT) were randomized by two groups the next 48 hours. The first group continued treatment with dabigatran 150 mg x twice a day for 6 months, the second group continued treatment with warfarin under the control of INR (2.0-3.0) for 6 months. Both groups received low molecular weight heparins for 2 days after surgery. Then, group 1 continued to receive low molecular weight heparins for 5-7 days, followed by a switch to dabigatran at a dosage of 150 mg x 2 times a day. Group 2 received both low molecular weight heparins and warfarin up to an INR of more than 2.0, followed by heparin withdrawal. Follow-up period was 6 months.

RESULTS: 63 patients completed the study (32 in dabigatran group and 31 in warfarin group). In both groups, there was a statistically significant decrease in mean pulmonary artery pressure (PAP). The mean PAP at six-month follow-up after surgery was 24 [20.3; 29.25] in the dabigatran group and 23 [20.0; 26.3] mm Hg in the warfarin group. The groups did not statistically differ in the deep vein thrombosis dynamics. Partial recanalization occurred in 52.0% versus 73.1% in the dabigatran and warfarin groups, respectively (p=0.15). Complete recanalization occurred in 28.0% versus 19.2% in the dabigatran and warfarin groups, respectively (p=0.56). The groups did not differ in the frequency of major bleeding events according to ISTH (0% vs. 3.2% in the dabigatran and warfarin groups, respectively, p = 1.00). However, there were more non-major bleeding events in the warfarin group than in the dabigatran group (16.1% vs 0% respectively, p=0.02).

CONCLUSION: The results of the study show that dabigatran is comparable in effectiveness to warfarin. Dabigatran has a greater safety in comparison with warfarin in the occurrence of all cases of bleeding in the postoperative and long-term periods. Thus, dabigatran may be recommended for treatment and prevention of PE after CDT with RDT in patients with high- and intermediate-high PE risk.