Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding

Summary

Gastrointestinal (GI) bleeding commonly complicates anticoagulant therapy. We aimed to systematically review the published literature to determine the risk of thromboembolism, recurrent GI bleeding and mortality for patients on long-term anticoagulation who experience GI bleeding based on whether anticoagulation therapy was resumed. We performed a systematic review of phase III randomised controlled trials and cohort studies in patients with atrial fibrillation or venous thromboembolism who received oral anticoagulant. We searched MEDLINE, EMBASE and CENTRAL (from 1996-July 2014), conferences abstracts (from January 2006-July 2014) and www.clinicaltrials.gov (up to the last week of July 2014) with no language restriction. Two reviewers independently performed study selection, data extraction and study quality assessment. A total of three studies were included in the meta-analysis. The resumption of warfarin was associated with a significant reduction in thromboembolic events (hazard ratio [HR] 0.68, 95 % confidence interval [CI] 0.52 to 0.88, p < 0.004, I²=82 %). There was an increase in recurrent GI bleeding but not statistically significant for patients who restarted warfarin compared to those who did not (HR 1.20, 95 % CI 0.97 to 1.48, p = 0.10, I² = 0 %). Resumption of warfarin was associated with significant reduction in mortality (HR 0.76, 95 % CI 0.66 to 0.88, p < 0.001, I² = 87 %). This meta-analysis demonstrates that resumption of warfarin following interruption due to GI bleeding is associated with a reduction in thromboembolic events and mortality without a statistically significant increase in recurrent GI bleeding.

Institution where the work was performed: McMaster University, Hamilton, Ontario, Canada.

Keywords

Anticoagulants - bleeding - warfarin - gastrointestinal haemorrhage - thromboembolism

• References

• 1 Bleeding during antithrombotic therapy in patients with atrial fibrillation.. The Stroke Prevention in Atrial Fibrillation Investigators. Arch Intern Med 1996; 156: 409-416.
• 2 Majeed A, Hwang HG, Connolly SJ. et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation 2013; 128: 2325-2332.
• 3 Nieto JA, Camara T, Gonzalez-Higueras E. et al. Clinical outcome of patients with major bleeding after venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008; 100: 789-796.
• 4 Coleman CI, Sobieraj DM, Winkler S. et al. Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation. Int J Clin Pract 2012; 66: 53-63.
• 5 Schelleman H, Brensinger CM, Bilker WB. et al. Antidepressant-warfarin interaction and associated gastrointestinal bleeding risk in a case-control study. PLoS One 2011; 6: e21447.
• 6 Witt DM, Delate T, Garcia DA. et al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med 2012; 172: 1484-1491.
• 7 Qureshi W, Mittal C, Patsias I. et al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. Am J Cardiol 2014; 113: 662-668.
• 8 Hashash JG, Shamseddeen W, Skoury A. et al. Gross lower gastrointestinal bleeding in patients on anticoagulant and/or antiplatelet therapy: endoscopic findings, management, and clinical outcomes. J Clin Gastroenterol 2009; 43: 36-42.
• 9 Rubin TA, Murdoch M, Nelson DB. Acute GI bleeding in the setting of supra-therapeutic international normalized ratio in patients taking warfarin: endoscopic diagnosis, clinical management, and outcomes. Gastrointest Endosc 2003; 58: 369-373.
• 10 Higgins JP, Altman DG, Gotzsche PC. et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. Br Med J 2011; 343: d5928.
• 11 Raunso J, Selmer C, Olesen JB. et al. Increased short-term risk of thrombo-embolism or death after interruption of warfarin treatment in patients with atrial fibrillation. Eur Heart J 2012; 33: 1886-1892.
• 12 Higgin JPT GS eds.. Cochrane Handbook for Systematic Review of Interventions Version 5.1.0 [updated March 2011]. ed, The Cochrane Collaboration; 2011
• 13 Liberati A, Altman DG, Tetzlaff J. et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. Br Med J 2009; 339: b2700.
• 14 Wells GA SB, O’Connell D, Peterson J et al.. In: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. >Accessed July 2014
• 15 Sherman DG, Kim SG, Boop BS. et al. Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study. Arch Intern Med 2005; 165: 1185-1191.
• 16 Sherwood MW, Douketis JD, Patel MR. et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 2014; 129: 1850-1859.
• 17 Desai J, Kolb JM, Weitz JI. et al. Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies. Thromb Haemost 2013; 110: 205-212.
• 18 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the S,. et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3: 692-694.
• 19 Lip GY, Andreotti F, Fauchier L. et al. Bleeding risk assessment and management in atrial fibrillation patients. Executive Summary of a Position Document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. Thromb Haemost 2011; 106: 997-1011.