Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study

Abstract

Study queStionWhat are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation? MethodSThis Danish cohort study (1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models.Study anSwer and liMitationS 4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with nonresumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment. what thiS Study addSAmong patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding.

Therapeutic Strategies Following Major, Clinically Relevant Nonmajor, and Nuisance Bleeding in Atrial Fibrillation: Findings From ORBIT‐AF

“…Consistent with prior work, we found substantial rates of OAC discontinuation following major bleeding, despite increasing evidence that such discontinuations are associated with adverse clinical outcomes 11. In a retrospective analysis of 442 patients experiencing warfarin‐associated gastrointestinal bleeding, Witt et al reported warfarin discontinuation rates of 41.2% within 90 days of the index event.…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…Wiele przyczyn poważnych krwawień lub czynników wywołujących takie incydenty można leczyć lub wyeliminować, w tym źle kontrolowane nadciśnienie tętnicze, owrzodzenia trawienne oraz tętniaki wewnątrzczaszkowe. Ponowne rozpoczęcie leczenia przeciwzakrzepowego po incydencie krwawienia jest często uzasadnione klinicznie [460,510]. Trudne decyzje, w tym dotyczące przerwania i ponownego rozpoczęcia OAC, powinien podejmować wielodyscyplinarny zespół z uwzględnieniem oszacowanego ryzyka (ponownego) udaru i krwawienia, a także ryzyka krwawienia związanego ze stosowaniem różnych metod zapobiegania udarowi mózgu.…”

What Big Data Could Achieve in Scotland

“…3 The optimum choice of anticoagulant therapy in a nonvalvular atrial fi brillation patient who wishes to resume anticoagulant therapy is debatable. 4,5 Outside the context of AUGIB a comparison between warfarin and direct oral anticoagulants (DOACs) showed that edoxaban 30 mg/d was associated with signifi cantly (p < 0.001) lower risk of gastrointestinal bleeding, 4 notwithstanding the recommendation that, when restarting oral anticoagulants after AUGIB 'if DOAC therapy is preferred apixaban is the preferred agent based on the most favourable rate of GIB (gastrointestinal bleeding) from clinical trials'. 5 The caveat is the lack of a reversal agent either for edoxaban or apixaban.…”

“…1 There is a growing body of evidence, including our own, 3 which supports the resumption of various classes of antithrombotics after AUGIB. 4 It should be emphasised that post-AUGIB mortality from uncontrolled exsanguination is rare, whereas mortality from major vascular events is common. 3,4 We believe that the vascular risks are amplifi ed after AUGIB due to a combination of factors including: i) induction of a prothrombotic state due to systemic stress, hospitalisation and transfusion, ii) cardiac strain associated with anaemia, which is prevalent after AUGIB, 1 and iii) the common practice of antithrombotic withdrawal.…”

“…This involves understanding how the main condition primarily responsible for the need for treatment is recorded at the end of each care episode, with up to fi ve additional diagnoses (relevant past diagnoses/complications/comorbidities). 4 Diagnoses need to be documented without ambiguity to avoid symptom codes being assigned. 5 We celebrate the positive strides in big data research discussed in the editorial.…”