Rates of rebleeding, thrombosis and mortality associated with resumption of anticoagulant therapy after anticoagulant-related bleeding.

BACKGROUND: Data on resuming oral anticoagulants (OACs) after bleeding are primarily from studies involving patients given warfarin, with few data on direct OACs (DOACs). We aimed to characterize prescribing patterns for OACs after OAC-related bleeding and compare the rates of bleeding, thrombosis and mortality in patients who resumed either type of OAC with those who did not. METHODS: We conducted a population-based cohort study of adults aged 66 years or older who were admitted to hospital for bleeding while receiving OACs from Apr. 1, 2012, to Mar. 31, 2017, using linked administrative health databases from Ontario. We used competing risk methods to calculate cause-specific adjusted hazard ratios (HRs) for thrombosis, bleeding and mortality with resumption of OACs adjusted as a time-varying covariate. We determined time to OAC resumption using the Kaplan-Meier method. RESULTS: We included 6793 patients with gastrointestinal (n = 4297, 63.3%), intracranial (n = 805, 11.9%) or other bleeding (n = 1691, 25.0%). At cohort entry, 3874 patients (57.0%) were prescribed warfarin and 2919 patients (43.0%) were prescribed a DOAC. The most common indication for OAC was atrial fibrillation (n = 5557, 81.8%), followed by venous thromboembolism (n = 1367, 20.1%). Oral anticoagulants were resumed in 4792 patients (70.5%) within 365 days of the index bleed. The median time to resumption was 46 (interquartile range 6-550) days. We found that resuming OAC was associated with reduced rates of thrombosis (adjusted HR 0.60, 95% confidence interval [CI] 0.50-0.72) and mortality (adjusted HR 0.54, 95% CI 0.48-0.60), and an increased rate of rebleeding (adjusted HR 1.88, 95% CI 1.64-2.17). INTERPRETATION: We found that resuming OAC is associated with a reduction in thrombosis and mortality but an increase in bleeding. Randomized controlled trials that evaluate the net benefit of strategies for resumption of OAC after a bleeding event are warranted.

Management of antithrombotic therapy after gastrointestinal bleeding: A mixed methods study of health-care providers.

Essentials The factors influencing anticoagulation management after gastrointestinal bleeding are unclear. Focus groups and a discrete choice experiments survey of health-care providers were conducted. Re-bleeding risk and thrombosis risk were the most important factors influencing decision making. Preference variability exists with a minority most sensitive to the anticoagulation indication. ABSTRACT: Background Oral anticoagulants (OACs) are permanently discontinued in up to 50% of patients after gastrointestinal (GI) bleeding despite evidence of benefit to restarting. Objectives We aimed to identify factors influencing health-care provider decision making regarding resuming OAC after GI bleeding and to identify preference groups. Patients/Methods We conducted focus group discussions (FGDs) with health-care providers. Themes identified and ranked through a dot voting exercise became the attributes for a discrete choice experiment survey of health-care providers developed using Sawtooth (Sawtooth Software, Provo, UT, USA). Hierarchical Bayes analysis was used to estimate preference coefficients (utilities) for each attribute. Preference groups were identified using latent class analysis. Results We conducted four FGDs involving 29 participants. The five most important factors identified in the FGDs were included in the survey. There were 250 survey respondents (mean age 45 years, 53% male). The most important factor was re-bleeding risk followed by thrombosis risk, index bleed severity, indication for OAC, and patient characteristics. Two preference groups were identified, a majority group (87% of respondents) placed the highest utility on re-bleeding risk followed by thrombosis risk, while a minority group (13% of respondents) placed the highest utility on OAC indication. Conclusions Overall, the most important factor influencing provider decision making was re-bleeding risk followed closely by thrombosis risk, although the indication for OAC was most important for a minority of respondents. This highlights variability among providers in an area lacking high-quality data to guide practice. Further research is needed to determine absolute rates of outcomes and patient values and preferences.

Effectiveness of Dose De-escalation of Biologic Therapy in Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: De-escalation of biologic therapy is a commonly encountered clinical scenario. Although biologic discontinuation has been associated with high rates of relapse, the effectiveness of dose de-escalation is unclear. This review was performed to determine the effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception to October 2019. Randomized controlled trials and observational studies involving dose de-escalation of biologic therapy in adults with inflammatory bowel disease in remission were included. Studies involving biologic discontinuation only and those lacking outcomes after dose de-escalation were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: We identified 1,537 unique citations with 20 eligible studies after full-text review. A total of 995 patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial. Seven studies included patients with Crohn's disease, 1 included patients with ulcerative colitis, and 12 included both. Overall, clinical relapse occurred in 0%-54% of patients who dose de-escalated biologic therapy (17 studies). The 1-year rate of clinical relapse ranged from 7% to 50% (6 studies). Eighteen studies were considered at high risk of bias, mostly because of the lack of a control group. DISCUSSION: Dose de-escalation seems to be associated with high rates of clinical relapse; however, the quality of the evidence was very low. Additional controlled prospective studies are needed to clarify the effectiveness of biologic de-escalation and identify predictors of success.