Efficacy Endpoints: Death, Recurrent PE, Recurrent/Extension of DVT
Harm Endpoints: Major hemorrhage (intracerebral hemorrhage, GI bleed). Risk varies depending on population. In one Cochrane review of trial data major bleeding occurred in 0.9% to 2% of subjects, a NNH of 50 to 111 (Hutten BA), and there were no major hemorrhages in the Nielsen study of 90 ambulatory outpatients. However subjects eligible for randomized trials tend to be at lower risk for bleeding than typical coumadin patients in the community. In one population-based cohort of coumadin patients 2% experienced a fatal bleeding event (NNH=50) and the overall major bleeding rate was 12% (NNH=8). (Landefeld CS et al. Am J Med 1989). It is estimated that 15000-52000 patients die annually in the U.S. of brain bleeding caused by coumadin.
Narrative: There has been one adequately designed study addressing whether anticoagulation improves important clinical outcomes in patients with VTE (Nielson et al., 1994). Subjects were enrolled if they were ambulatory with symptomatic DVT. Half of the 90 subjects also had silent pulmonary emboli. Subjects were randomized to anticoagulation or NSAIDs and there was 1 fatal PE during the study period (anticoagulation group).
In 1960, Barritt and Jordan performed a randomized trial evaluating anticoagulation for presumed PE. While the study is often cited as evidence of the benefit of anticoagulation, methodologic weaknesses render it unreliable (the Cochrane group excludes the study). Patients with suspected PE were included and no confirmatory testing was performed; randomization was not described; no blinding and no placebo were used; all subjects were inpatients for other reasons and all were critically ill at enrollment; the study was stopped inappropriately early. The results of this study appear to have led the medical community to erroneously conclude that anticoagulation is proven beneficial for VTE.
Caveats: While the Nielson study does not prove that anticoagulation is unhelpful for VTE it is our best and only methodologically reliable source. Large, properly designed trials are needed.
Author: Ashley Shreves, MD
Published/Updated: November 28, 2009
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