Optimal timing of vitamin K antagonist resumption after upper gastrointestinal bleeding

Summary

The optimal timing of vitamin K antagonists (VKAs) resumption after an upper gastrointestinal (GI) bleeding, in patients with continued indication for oral anticoagulation, is uncertain. We included consecutive cases of VKA-associated upper GI bleeding from three hospitals retrospectively. Data on the bleeding location, timing of VKA resumption, recurrent GI bleeding and thromboembolic events were collected. A model was constructed to evaluate the ‘total risk’, based on the sum of the cumulative rates of recurrent GI bleeding and thromboembolic events, depending on the timing of VKA resumption. A total of 121 (58 %) of 207 patients with VKA-associated upper GI bleeding were restarted on anticoagulation after a median (interquartile range) of one (0.2–3.4) week after the index bleeding. Restarting VKAs was associated with a reduced risk of thromboembolism (HR 0.19; 95 % CI, 0.07–0.55) and death (HR 0.61; 95 % CI, 0.39–0.94), but with an increased risk of recurrent GI bleeding (HR 2.5; 95 % CI, 1.4–4.5). The composite risk obtained from the combined statistical model of recurrent GI bleeding, and thromboembolism decreased if VKAs were resumed after three weeks and reached a nadir at six weeks after the index GI bleeding. On this background we will discuss how the disutility of the outcomes may influence the decision regarding timing of resumption. In conclusion, the optimal timing of VKA resumption after VKA-associated upper GI bleeding appears to be between 3–6 weeks after the index bleeding event but has to take into account the degree of thromboembolic risk, patient values and preferences.

Keywords

Gastrointestinal bleeding - Warfarin - thromboembolism - stroke - mortality

• References

• 1 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention. Am J Med 1993; 95: 315-328.
• 2 White RH, McKittrick T, Takakuwa J. et al. Management and prognosis of life-threatening bleeding during warfarin therapy. National Consortium of Anticoagulation Clinics. Arch Internal Med 1996; 156: 1197-1201.
• 3 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.
• 4 Witt D, Delate T, Garcia D. et al. Risk of thromboembolism, recurrent haemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Internal Med 2012; 172: 1484-1491.
• 5 Johnsen SP, Sørensen HT, Mellemkjoer L. et al. Hospitalisation for upper gastrointestinal bleeding associated with use of oral anticoagulants. Thromb Haemost 2001; 86: 563-568.
• 6 Salem DN, O’Gara PT, Madias C. et al. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidellines (8th Edition). Chest 133: 593S-629S.
• 7 Gage BF, Waterman AD, Shannon W. et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
• 8 Kearon C, Kahn SR, Agnelli G. et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidellines (8th Edition). Chest 2008; 133: 454S-545S.
• 9 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694.
• 10 Chai-Adisaksopha C, Hillis C, Monreal M. et al. Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding. A meta-analysis Thromb Haemost 2015; 114: 819-825.
• 11 Staerk L, Lip G, Olesen J. et al. Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study. Br Med J 2015; 351: h5876.
• 12 Sengupta N, Feuerstein JD, Patwardhan VR. et al. The risks of thromboembolism vs recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized inpatients with gastrointestinal bleeding: a prospective study. Am J Gastroenterol 2015; 110: 328-335.
• 13 Devereaux PJ, Anderson DR, Gardner MJ. et al. Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. Br Med J 2001; 323: 1218-1222.
• 14 MacLean S, Mulla S, Akl E. et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidellines. Chest 2012; 141: e1S-23S.
• 15 Hearnshaw SA, Logan RF, Lowe D. et al. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut 2011; 60: 1327-1335.
• 16 Loperfido S, Fabris L, Maifreni L. et al. Comparison of upper gastrointestinal bleeding in UK and in Treviso area (Italy): similarities and differences. Gut 2012; 61: 1641-1642.
• 17 Van Walraven C, Hart R, Singer D. et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. J Am Med Assoc 2002; 288: 2441-2448.