Management and outcomes of major bleeding during treatment with dabigatran or warfarin.

Abstract

BACKGROUND:

The aim of this study was to compare the management and prognosis of major bleeding in patients treated with dabigatran or warfarin.

METHODS AND RESULTS:

Two independent investigators reviewed bleeding reports from 1034 individuals with 1121 major bleeds enrolled in 5 phase III trials comparing dabigatran with warfarin in 27 419 patients treated for 6 to 36 months. Patients with major bleeds on dabigatran (n=627 of 16 755) were older, had lower creatinine clearance, and more frequently used aspirin or non-steroid anti-inflammatory agents than those on warfarin (n=407 of 10 002). The 30-day mortality after the first major bleed tended to be lower in the dabigatran group (9.1%) than in the warfarin group (13.0%; pooled odds ratio, 0.68; 95% confidence interval, 0.46-1.01; P=0.057). After adjustment for sex, age, weight, renal function, and concomitant antithrombotic therapy, the pooled odds ratio for 30-day mortality with dabigatran versus warfarin was 0.66 (95% confidence interval, 0.44-1.00; P=0.051). Major bleeds in dabigatran patients were more frequently treated with blood transfusions (423/696, 61%) than bleeds in warfarin patients (175/425, 42%; P<0.001) but less frequently with plasma (dabigatran, 19.8%; warfarin, 30.2%; P<0.001). Patients who experienced a bleed had shorter stays in the intensive care unit if they had previously received dabigatran (mean 1.6 nights) compared with those who had received warfarin (mean 2.7 nights; P=0.01).

CONCLUSIONS:

Patients who experienced major bleeding on dabigatran required more red cell transfusions but received less plasma, required a shorter stay in intensive care, and had a trend to lower mortality compared with those who had major bleeding on warfarin.

CLINICAL TRIAL REGISTRATION URL:

http://www.ClinicalTrials.gov. Unique identifiers: NCT00262600, NCT00291330, NCT00680186, NCT00329238 and NCT00558259.

• Authors: Ammar Majeed, Hun-Gyu Hwang, Stuart J Connolly, John W Eikelboom, Michael D Ezekowitz, Lars Wallentin, Martina Brueckmann, Mandy Fraessdorf, Salim Yusuf, Sam Schulman
• Journal: Circulation (Circulation) Vol. 128 Issue 21 Pg. 2325-32 (Nov 19 2013) ISSN: 1524-4539 [Electronic] United States
• PMID: 24081972 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Meta-Analysis, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Antithrombins
• Benzimidazoles
• Hemoglobins
• beta-Alanine
• Warfarin
• Dabigatran

Topics

• Aged
• Aged, 80 and over
• Anticoagulants (administration & dosage, adverse effects)
• Antithrombins (administration & dosage, adverse effects)
• Atrial Fibrillation (drug therapy, mortality)
• Benzimidazoles (administration & dosage, adverse effects)
• Blood Transfusion (statistics & numerical data)
• Dabigatran
• Female
• Hemoglobins (metabolism)
• Hemorrhage (chemically induced, mortality, therapy)
• Humans
• Length of Stay (statistics & numerical data)
• Male
• Middle Aged
• Risk Factors
• Treatment Outcome
• Venous Thromboembolism (drug therapy, mortality)
• Warfarin (administration & dosage, adverse effects)
• beta-Alanine (administration & dosage, adverse effects, analogs & derivatives)