Treatment of acute pulmonary embolism after catheter-directed thrombolysis with dabigatran vs warfarin: Results of a multicenter randomized RE-SPIRE trial

• Published in: Journal of vascular surgery. Venous and lymphatic disorders (New York, NY) NY), 2024-07, Vol.12 (4), p.101848, Article 101848
• Main Authors: Gostev, Alexander A., Valiev, Emin, Zeidlits, Galina A., Shmidt, Evgeniya A., Osipova, Olesya S., Cheban, Alexey V., Saaya, Shoraan B., Barbarash, Olga L., Karpenko, Andrey A.
• Format: Article
• Language: English
• Subjects: Acute Disease; Adult; Aged; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Antithrombins - administration & dosage; Antithrombins - adverse effects; beta-Alanine - administration & dosage; beta-Alanine - adverse effects; beta-Alanine - analogs & derivatives; Catheter-directed thrombolysis; Clinical Research Studies; Dabigatran; Dabigatran - administration & dosage; Dabigatran - adverse effects; Deep vein thrombosis; Female; Hemorrhage - chemically induced; Humans; International Normalized Ratio; Male; Middle Aged; Oral anticoagulation therapy; Prospective Studies; Pulmonary embolism; Pulmonary Embolism - drug therapy; Pulmonary Embolism - etiology; Pulmonary Embolism - prevention & control; Recurrence; Risk Factors; Save-dose thrombolysis; Thrombolytic Therapy - adverse effects; Time Factors; Treatment Outcome; Warfarin; Warfarin - administration & dosage; Warfarin - adverse effects
• ISSN: 2213-333X; 2213-3348; 2213-3348
• DOI: 10.1016/j.jvsv.2024.101848

Thrombolytic therapy is effective method in the high-risk acute pulmonary embolism (PE) treatment. 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 showed similar effectiveness as warfarin in the treatment of acute PE. Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the prevention of PE after mechanical fragmentation and RDT (catheter-directed treatment [CDT]+RDT) in patients with high and intermediate to high PE risk. We sought 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 to high acute PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT). The RE-SPIRE is a prospective, multicenter randomized double-arm study. Over a 5-year period, 66 consecutive patients with symptomatic high and intermediate to high PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT) were randomized into two groups within the next 48 hours. The first group continued treatment with dabigatran 150 mg twice a day for 6 months; the second group continued treatment with warfarin under the control of international normalized ratio (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-heparin for 5 to 7 days, followed by a switch to dabigatran at a dosage of 150 mg two times a day. Group 2 received both low-molecular-weight heparin and warfarin up to an international normalized ratio of >2.0, followed by heparin withdrawal. The follow-up period was 6 months. There were 63 patients who completed the study (32 in the dabigatran group and 31 in the warfarin group). In both groups, there was a statistically significant decrease in the mean pulmonary artery pressure. The mean pulmonary artery pressure at the 6-month follow-up after surgery was 24 mm Hg (interquartile range, 20.3-29.25 mm Hg) in the dabigatran group and 23 mm Hg (interquartile range, 20.0-26.3 mm Hg) in the warfarin group. The groups did not differ statistically in the deep vein thrombosis dynamics. Partial recanalization o