Background The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation (AF). Patients and clinicians now have a ...choice between different NOACs, but there is no direct comparative effectiveness evidence to guide decision-making. We aimed to compare the effectiveness and safety of dabigatran, rivaroxaban, and apixaban in clinical practice. Methods Using a large US administrative claims database, we created three one-to-one propensity-score-matched cohorts of patients with nonvalvular AF who were users of dabigatran, rivaroxaban, or apixaban between October 1, 2010 and February 28, 2015 (rivaroxaban vs dabigatran, n = 31,574; apixaban vs dabigatran, n = 13,084; and apixaban vs rivaroxaban, n = 13,130). The primary outcomes were stroke and systemic embolism (effectiveness) and major bleeding (safety) that occurred during treatment. Cox proportional hazards models were used to compare outcomes in propensity-score-matched cohorts. Results We found no differences between the three NOACs in the risk of stroke or systemic embolism (hazard ratio HR, 1.00; 95% CI, 0.75-1.32 for rivaroxaban vs dabigatran; HR, 0.82; 95% CI, 0.51-1.31 for apixaban vs dabigatran; and HR, 1.05; 95% CI, 0.64-1.72 for apixaban vs rivaroxaban). Apixaban was associated with a lower risk of major bleeding (HR, 0.50; 95% CI, 0.36-0.70; P < .001 vs dabigatran and HR, 0.39; 95% CI, 0.28-0.54; P < .001 vs rivaroxaban). Rivaroxaban was associated with an increased risk of major bleeding (HR, 1.30; 95% CI, 1.10-1.53; P < .01) and intracranial bleeding (HR, 1.79; 95% CI, 1.12-2.86; P < .05) compared with dabigatran. Conclusions Dabigatran, rivaroxaban, and apixaban appear to have similar effectiveness, although apixaban may be associated with a lower bleeding risk and rivaroxaban may be associated with an elevated bleeding risk.
Background & Aims Direct oral anticoagulant (DOAC) agents increase the risk of gastrointestinal (GI) bleeding. We investigated which DOAC had the most favorable GI safety profile and compared ...differences among these drugs in age-related risk of GI bleeding. Methods We conducted a retrospective, propensity-matched study using administrative claims data from the OptumLabs Data Warehouse of privately insured individuals and Medicare Advantage enrollees. We created 3 propensity-matched cohorts of patients with nonvalve atrial fibrillation with incident exposure to dabigatran, rivaroxaban, or apixaban from October 1, 2010 through February 28, 2015. We compared data on rivaroxaban vs dabigatran for 31,574 patients, data on apixaban vs dabigatran for 13,084 patients, and data on apixaban vs rivaroxaban for 13,130 patients. Cox proportional hazards models, stratified by age, were used to estimate rates of total GI bleeding. Results Baseline characteristics were well balanced among sub-cohorts. GI bleeding occurred more frequently in patients given rivaroxaban than dabigatran (hazard ratio HR, 1.20; 95% confidence interval CI, 1.00−1.45). Apixaban was associated with a lower risk of GI bleeding than dabigatran (HR, 0.39; 95% CI, 0.27−0.58; P < .001) or rivaroxaban (HR, 0.33; 95% CI, 0.22−0.49; P < .001). Rates of events for all DOACs increased among patients 75 years or older. Apixaban had a lower risk of association with GI bleeding in the very elderly than dabigatran (HR, 0.45; 95% CI, 0.29−0.71) or rivaroxaban (HR, 0.39; 95% CI, 0.25−0.61). Median times to GI bleeding were <90 days for apixaban and rivaroxaban and <120 days for dabigatran. Conclusions In a population-based study of patients receiving DOAC agents, we found apixaban had the most favorable GI safety profile and rivaroxaban least favorable. GI bleeding events among patient taking DOACs increased with age; the risk was greatest among persons ersons as old. Apixaban had the most favorable GI safety profile among all age groups.
The management of antiplatelet and anticoagulant (ie, antithrombotic) agents is challenging in the periendoscopic setting. In this state-of-the-art update, we review current best practice ...recommendations focusing on the risk of immediate and delayed postpolypectomy bleeding in the context of drug discontinuation (ie, temporary interruption) and drug continuation. The data regarding polypectomy technique (cold snare vs conventional thermal-based) and prophylactic placement of hemostatic clips are evaluated to assess whether these endoscopic techniques are beneficial in reducing postpolypectomy bleeding. Finally, clinical takeaways are provided to facilitate safer polypectomy among patients on antiplatelet and anticoagulant agents.
This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and ...presents new clinically relevant recommendations.
An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional.
Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease. Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers. Pharmacologic management: The group recommends that patients with bleeding ulcers with high-risk stigmata who have had successful endoscopic therapy receive high-dose proton-pump inhibitor (PPI) therapy (intravenous loading dose followed by continuous infusion) for 3 days. For these high-risk patients, continued oral PPI therapy is suggested twice daily through 14 days, then once daily for a total duration that depends on the nature of the bleeding lesion. Secondary prophylaxis: The group suggests PPI therapy for patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy for cardiovascular prophylaxis.
PURPOSE OF REVIEWThis review summarizes adverse effects of potential proton pump inhibitors (PPIs), including nutritional deficiencies (B12 and magnesium), rebound acid hypersecretion, acute ...interstitial nephritis, gastric carcinoid tumor, cardiovascular risk with clopidogrel and PPI coprescription, bone fractures, enteric infections and pneumonia. An epidemiologic framework is applied to assess clinical relevance and reinforce best practice recommendations.
RECENT FINDINGSThe evidence for PPI adverse events is limited by the absence of Level 1 (randomized controlled trial) studies. The best evidence supports Clostridium difficile and bone fractures in susceptible populations. A substantial reduction in gastrointestinal bleeding risk without increase in cardiovascular events was observed in the COGENT trial when clopidogrel was coprescribed with omeprazole. The risk of pneumonia is inconsistent, and although acute interstitial nephritis, nutritional deficiencies (including B12 and hypomagnesemia), gastric carcinoid and rebound hyperacidity are biologically plausible, studies have failed to demonstrate supportive clinical relevance.
SUMMARYPrescribe PPI for robust indications only. Strong data supporting risk of adverse events are lacking; however, exercise caution in the elderly and in patients with other risk factors for bone fractures or C. difficile infection.
Background
The introduction of non–vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may ...not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin.
Methods and Results
Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio HR 0.67, 95% CI 0.46–0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76–1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72–1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34–0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67–0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90–1.20, P=0.60). All non–vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding.
Conclusions
In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin.
Background
In comparison to warfarin, non–vitamin K antagonist oral anticoagulants (NOACs) have the advantages of ease of dosing, fewer drug interactions, and lack of need for ongoing monitoring. We ...sought to evaluate whether these advantages translate to improved adherence and whether adherence is associated with improved outcomes in patients with atrial fibrillation.
Methods and Results
We performed a retrospective cohort analysis by using a large US commercial insurance database to identify 64 661 patients with atrial fibrillation who initiated warfarin, dabigatran, rivaroxaban, or apixaban treatment between November 1, 2010, and December 31, 2014. During a median of 1.1 y of follow‐up, 47.5% of NOAC patients had a proportion of days covered of ≥80%, compared with 40.2% in warfarin patients (P<0.001). Patients with CHA2DS2‐VASc (risk based on the presence of congestive heart failure, hypertension age 65–74 y, age ≥75 y, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, sex category) score ≥4 were at increased risk of stroke when they were not taking anticoagulation ≥1 month versus <1 week (1–3 months: hazard ratio HR 1.96, 3–6 months: HR 2.64, ≥6 months: HR 3.66; all P<0.001). Patients with CHA2DS2‐VASc score 2 or 3 were at increased risk of stroke when they were not taking anticoagulation ≥6 months (HR 2.73, P<0.001). In these patients with CHA2DS2‐VASc score ≥2, nonadherence was not associated with intracranial hemorrhage. Among patients with CHA2DS2‐VASc score 0 or 1, time not taking anticoagulation was not associated with stroke, but not taking anticoagulation ≥3 months was associated with a significant reduction of bleeding.
Conclusions
Adherence to anticoagulation is poor in practice and may be modestly improved with NOACs. Adherence to therapy appears to be most important in patients with CHA2DS2‐VASc score ≥2, whereas the benefits of anticoagulation may not outweigh the harms in patients with CHA2DS2‐VASc score 0 or 1.
Managing gastrointestinal bleeding in patients using antithrombotic agents remains challenging in clinical practice. This review article provides a comprehensive and evidence-based approach to ...managing acute antithrombotic-related gastrointestinal bleeding, focusing on the triage of patients, appropriate resuscitation, and timely endoscopy. The latest clinical practice guidelines are highlighted to guide decisions concerning the use of reversal agents, temporary interruption, and resumption of antithrombotic drugs. Additionally, preventive measures are discussed to lower the risk of future bleeding and minimize complications among patients prescribed antithrombotic drugs.
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