Level 2 [mid-level] evidence

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In patients with atrial fibrillation experiencing a gastrointestinal bleed while on antithrombotic therapy, the decision to resume antithrombotic therapy or not can be difficult. The risk of thromboembolism needs to be weighed against the risk of recurrent bleeding to determine if thromboembolic prophylaxis should be continued and if continued, what antithrombotic therapy to use (oral anticoagulation, antiplatelet agent, dual therapy, or triple therapy). A recent retrospective cohort study evaluated 3,409 patients aged ≥ 30 years (mean age, 78 years) with atrial fibrillation who were hospitalized for a first gastrointestinal bleed while on single or combined antithrombotic therapy. Patients were followed for up to 5 years (median follow-up, 2 years) and follow-up began 90 days after hospital discharge. Patients with thromboembolic events, major bleeding, or recurrent gastrointestinal bleed, or those who died within 90 days of hospital discharge, were excluded from the study. Major bleeding was defined as intracranial bleeding or severe respiratory, gastrointestinal, or urinary tract bleeding. Baseline comorbidities included ischemic heart disease in 38%, heart failure in 30.7%, and stroke or thromboembolism in 22.5%.1 

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By day 90 post-discharge, 72.9% of patients had resumed antithrombotic therapy, with single therapy with oral anticoagulation in 21.3% or antiplatelet agent in 38.5% and dual therapy with oral anticoagulation plus antiplatelet agent in 11.3%. At 2 years, the cumulative incidence of all-cause mortality was 39.9%, thromboembolism was 12%, major bleeding was 17.7%, and recurrent gastrointestinal bleeding was 12.1%. Resumption of a single oral anticoagulant, single antiplatelet agent, or dual anticoagulant/antiplatelet therapy were all associated with reduced risk of all-cause mortality and thromboembolism compared to not restarting antithrombotic therapy (Table), but there were no significant differences in either outcome with dual aspirin plus adenosine diphosphate receptor antagonist therapy. Also, while oral anticoagulation therapy was associated with a small increased risk of major bleeding compared to no therapy, there were no significant differences in the risk of major bleeding with single antiplatelet therapy or either dual therapy regimen. There were also no significant differences in recurrent gastrointestinal bleed with any antithrombotic regimen. 

The results of this study are consistent with a smaller retrospective cohort study finding that patients who restarted warfarin had a reduced risk of thromboembolism or death but no significant differences in recurrent gastrointestinal bleeding compared to patients not restarting therapy.2 In the current study, single therapy with antiplatelet agents decreased mortality compared to not restarting therapy, but this regimen was not as effective as therapy with an oral anticoagulant. Dual therapy with oral anticoagulation plus an antiplatelet agent was also no more effective than oral anticoagulation alone, further suggesting that antiplatelet agents may not be effective for reducing mortality or the risk of thromboembolism. These results were consistent across subgroup analyses of patients also taking proton pump inhibitors and in sensitivity analyses using 30 days after hospital discharge as the start of follow-up. However, the effects of novel oral anticoagulants (NOACs) could not be determined due to the low number of patients taking these medications at the time of the study. Overall, this study suggests that resuming antithrombotic therapy with a single oral anticoagulant in patients with atrial fibrillation and a serious gastrointestinal bleed results in better overall mortality outcomes despite potentially increasing the risk of major bleeding. 

Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester. 

DynaMed is a database that provides evidence-based information on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals. 


  1. Staerk L, Lip GY, Olesen JB, et al. Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study. BMJ. 2015;351:h5876.

  2. Qureshi W, Mittal C, Patsias I, et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. Am J Cardiol. 2014;113[4]:662-668.