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Choice of Renal Function Estimator Influences Adverse Outcomes with Dabigatran Etexilate in Patients with Atrial Fibrillation.

ABSTRACT: Background Clinical significance of dosing dabigatran with different estimates of renal function for treatment of atrial fibrillation (AF) is unknown. Renal function is routinely estimated by the chronic kidney disease epidemiology initiative equation (CKD-EPI) and used to guide dosing. The aim of this study was to investigate the risk of adverse outcomes for patients with AF when different estimators of renal function are used. Material and Methods AF patient data were extracted from national administrative databases. Renal function was estimated using Cockcroft-Gault, CKD-EPI, and CKD-EPI adjusted for body surface area (CKD-EPI-BSA). Outcomes of cerebrovascular accident (CVA), systemic embolism (SE), and hemorrhage were extracted. Results In total, 2,425 patients were identified, of which there were hospitalizations for 138 (5.7%) hemorrhagic events, 45 (1.9%) CVA/SE, and 33 (1.4%) unspecified CVA. The level of agreement between Cockcroft-Gault with CKD-EPI and CKD-EPI-BSA yielded a weighted kappa statistic of 0.47 and 0.71, respectively. CKD-EPI and CKD-EPI-BSA significantly overestimated renal function in elderly patients resulting in higher recommended doses compared with Cockcroft-Gault. The hazard ratio for a hemorrhagic event was 2.32 (95% confidence interval, 1.22-4.42; p = 0.01) when a high dose was given compared with normal dose, based on Cockcroft-Gault. Conclusion Both CKD-EPI and CKD-EPI-BSA equations significantly overestimated renal function in the elderly population compared with the Cockcroft-Gault equation. This may lead to dose selection errors for dabigatran, particularly for those with severe impairment, increasing the risk of adverse outcome. Hence, CKD-EPI and CKD-EPI-BSA equations should not be substituted for the Cockcroft-Gault equation in the elderly for the purpose of renal dosage adjustments.

SUBMITTER: Simpson BH

PROVIDER: S-EPMC6524914 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom.DesignQuantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study to a lifetime horizon.SettingUK National Health Service. Population Cohorts of 50,000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes mellitus, previous Stroke/transient ischaemic attack) score of 2.1.Main outcome measuresQuality adjusted life years (QALYs) gained and incremental cost per QALY of dabigatran compared with warfarin.ResultsCompared with warfarin, low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 (95% central range -0.083 to 0.267) and 0.146 (-0.029 to 0.322) QALYs. Positive incremental net benefits resulted for high dose dabigatran in 94% of simulations versus warfarin and in 76% of those versus low dose dabigatran. In the economic analysis, high dose dabigatran dominated the low dose, had an incremental cost effectiveness ratio of £23,082 (€26,700; $35,800) per QALY gained versus warfarin, and was more cost effective in patients with a baseline CHADS(2) score of 3 or above. However, at centres that achieved good control of international normalised ratio, such as those in the UK, dabigatran 150 mg was not cost effective, at £42,386 per QALY gained.ConclusionsThis analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin. However, no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified. High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled.

Project description:ImportanceIt remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice.ObjectiveTo compare the risk of bleeding associated with dabigatran and warfarin using Medicare data.Design, setting, and participantsIn this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011.ExposuresDabigatran users (n = 1302) and warfarin users (n = 8102).Main outcomes and measuresWe identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities.ResultsDabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease.Conclusions and relevanceDabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.

Project description:STUDY OBJECTIVE:In the United States, nearly 70% of emergency department (ED) visits for atrial fibrillation result in hospitalization. The incidence of serious 30-day adverse events after an ED evaluation for atrial fibrillation remains low. This study's goal was to prospectively validate our previously reported Risk Estimator Decision Aid for Atrial Fibrillation (RED-AF) model for estimating a patient's risk of experiencing a 30-day adverse event. METHODS:This was a prospective cohort study, which enrolled a convenience sample of ED patients presenting with atrial fibrillation. RED-AF, previously derived from a retrospective cohort of 832 patients, assigns points according to age, sex, coexisting disease (eg, heart failure, hypertension, chronic obstructive pulmonary disease), smoking, home medications (eg, ?-blocker, diuretic), physical examination findings (eg, dyspnea, palpitations, peripheral edema), and adequacy of ED ventricular rate control. Primary outcome was occurrence of greater than or equal to 1 atrial fibrillation-related adverse outcome (ED visits, rehospitalization, cardiovascular complications, death) within 30 days. We identified a clinically relevant threshold and measured RED-AF's performance in this prospective cohort, assessing its calibration, discrimination, and diagnostic accuracy. RESULTS:The study enrolled 497 patients between June 2010 and February 2013. Of these, 120 (24%) had greater than or equal to 1 adverse event within 30 days. A RED-AF score of 87 was identified as an optimal threshold, resulting in sensitivity and specificity of 96% (95% confidence interval [CI] 91% to 98%) and 19% (95% CI 15% to 23%), respectively. Positive and negative predictive values were 27% (95% CI 23% to 32%) and 93% (95% CI 85% to 97%), respectively. The c statistic for RED-AF was 0.65 (95% CI 0.59 to 0.71). CONCLUSION:In this separate validation cohort, RED-AF performed moderately well and similar to the original derivation cohort for identifying the risk of short-term atrial fibrillation-related adverse events in ED patients receiving a diagnosis of atrial fibrillation.

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Choice of Renal Function Estimator Influences Adverse Outcomes with Dabigatran Etexilate in Patients with Atrial Fibrillation.

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