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Extended anticoagulation reduced risk for recurrent VTE, major bleeding
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SAN FRANCISCO — Patients who experienced unprovoked pulmonary embolism had a significant reduction in the composite risk for recurrent venous thromboembolism and major bleeding when they received anticoagulation for an additional 18 months, according to study results presented at the ASH Annual Meeting and Exposition.
However, the benefits associated with extended anticoagulation did not persist after treatment stopped, results also showed.
“After a first episode of unprovoked pulmonary embolism, 2 years of anticoagulation compared with 6 months is not associated with a long-term benefit once anticoagulation had been stopped,” Francis Couturaud, MD, PhD, of the department of internal medicine and chest diseases at Brest University Hospital Center, France, told HemOnc Today. “The study suggests that a majority of these patients should receive indefinite anticoagulation.”
Couturaud and colleagues evaluated data from 371 patients who received 6 months of initial treatment with vitamin K antagonist for a first episode of unprovoked PE.
Researchers randomly assigned patients to an additional 18 months of warfarin (n=184) or placebo (n=187).
The occurrence of recurrent VTE or major bleeding during the 18-month treatment period served as the composite primary endpoint.
Six patients (3.3%) in the warfarin arm experienced a primary endpoint event, whereas 25 patients (13.5%) in the placebo arm experienced an event. Overall, an additional 18 months of warfarin was associated with a significant reduction in the risk for recurrent VTE or major bleeding (HR=0.23; 95% CI, 0.09-0.55).
More patients in the placebo arm experienced recurrent VTE during 18 months of treatment (13.5% vs. 1.7%; HR=0.11; 95% CI, 0.03-0.37). The rates of major bleeding did not significantly differ between the two groups (2.2% vs. 0.5%; HR=4.07; 95% CI, 0.45-36.38).
Two deaths occurred during this time that were unrelated to the study outcomes.
Researchers followed patients for 2 years after stopping treatment, for an overall median follow-up of 41 months. Fewer patients who received additional warfarin experienced recurrent VTE or major bleeding throughout the entire study period (20.8% vs. 23.5%). However, the reduced risk for these events associated with additional anticoagulation lost significance (HR=0.76; 95% CI, 0.48-1.2).
“If we look at the cumulative risk during the entire study period, during the treatment period there is a dramatic relative risk reduction of the composite endpoint,” Couturaud said during his presentation. “But during follow-up after stopping treatment, the curves catch up and there is no significant difference at the end of the study.”
The occurrence of recurrent VTE increased to 17.9% of patients in the warfarin arm and 22.1% in the placebo arm (HR=0.67; 95% CI, 0.41-1.08). The occurrence of major bleeding increased to 3.5% of patients in the warfarin arm and 2.5% of patients in the placebo arm (HR=1.57; 95% CI, 0.44-5.55).
Sixty-seven events of recurrent VTE occurred, of which 52 (77.6%) were PE and 58 (86.6%) were unprovoked.
The rate for all-cause death was not significantly different between the two groups (11.9% vs. 3.6%; P=.08). Four deaths in the warfarin arm were related to recurrent VTE, and one was related to major bleeding. No deaths in the placebo arm were related to recurrent VTE and bleeding.
“Extending anticoagulation for 18 months was associated with a risk reduction of 77% of recurrent VTE or major bleeding during the treatment period,” Couturaud said. “However, the benefit was lost during a long-term follow-up of 2 years after stopping anticoagulation. Additional investigations are needed to identify subgroups of patients who are at lower risk and who may not need indefinite anticoagulation.”
For more information:
Couturaud F. Abstract #LBA-3. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.
Disclosure: Researchers report consultant or board of directors’ roles with and research funding from Actelion, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, LEO Pharma, Novartis, Pfizer and Sanofi.