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- Proietti, M., et al.
(författare)
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Comparison of bleeding risk scores in patients with atrial fibrillation : insights from the RE-LY trial
- 2018
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 283:3, s. 282-292
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.Objectives: To compare the performance of contemporary clinical bleeding risk scores in 18113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE-LY trial.Methods: HAS-BLED, ORBIT, ATRIA and HEMORR(2)HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.Results: There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P<0.001). The ORBIT score showed the best discrimination with c-indices of 0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial bleeding, which were significantly better than for the HAS-BLED score (difference in c-indices: 0.050, 0.053 and 0.048, respectively, all P<0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P=0.0019), ATRIA (P<0.001) and HEMORR(2)HAGES (P<0.001) scores. HAS-BLED score showed a nonsignificant trend for interaction (P=0.0607).Conclusions: Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.
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- Westenbrink, B. D., et al.
(författare)
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Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation : insights from the RE-LY trial
- 2015
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 13:5, s. 699-707
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAnemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF). ObjectivesTo investigate whether anemia is associated with thromboembolic events and bleeding in patients with AF. Patients and methodsWe retrospectively analyzed the RE-LY trial database, which randomized 18113 patients with AF and a risk of stroke to receive dabigatran or warfarin for a median follow-up of 2years. Cox regression analysis was used to determine whether anemia predicted cardiovascular events and bleeding complications in these patients. ResultsAnemia was present in 12% of the population at baseline, and the presence of anemia was associated with a higher risk of thromboembolic cardiovascular events, including the composite endpoint of all-cause mortality or myocardial infarction (adjusted hazard ratio [HR]1.50, 95% confidence interval [CI]1.32-1.71) and the primary RE-LY outcome of stroke or systemic embolism (adjusted HR1.41, 95%CI1.12-1.78). Anemia was also associated with a higher risk of major bleeding complications (adjusted HR2.14, 95%CI1.87-2.46) and discontinuation of anticoagulants (adjusted HR1.40, 95%CI1.28-1.79). The association between anemia and outcome was similar irrespective of cardiovascular comorbidities, randomized treatment allocation, or prior use of warfarin. The incidence of events was lower in patients with transient anemia than in patients in whom anemia was sustained (adjusted HR0.66, 95%CI0.49-0.91). ConclusionsAnemia is associated with an increased risk of thromboembolic events, bleeding complications and mortality in anticoagulated patients with AF. These findings suggest that patients with anemia should be monitored closely during all types of anticoagulant treatment.
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- Liesenfeld, K-H, et al.
(författare)
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Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial
- 2011
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 9:11, s. 2168-2175
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dabigatran etexilate (DE) is an orally absorbed prodrug of dabigatran, a thrombin inhibitor that exerts potent anticoagulant and antithrombotic activity. Objectives: To characterize the pharmacokinetics of dabigatran in patients with non-valvular atrial fibrillation (AF) from the Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) trial and to quantify the effect of selected factors on pharmacokinetic (PK) model parameters. Patients and methods: A total of 27 706 dabigatran plasma concentrations from 9522 patients who received DE 110 or 150 mg twice daily were analyzed with non-linear mixed-effects modeling. Results: The pharmacokinetics of dabigatran were best described by a two-compartment disposition model with first-order absorption. The covariates creatinine clearance (CRCL), age, sex, heart failure and the ethnic subgroup 'South Asian' exhibited statistically significant effects on apparent clearance of dabigatran. Body weight and hemoglobin significantly influenced the apparent volume of distribution of the central compartment. Concomitant medication with proton-pump inhibitors, amiodarone and verapamil significantly affected the bioavailability. However, all of the statistically significant factors that were identified, except for renal function status, showed only small to moderate effects (< 26% change in exposure at steady state). On the basis of simulations from the final population PK model, a dose of 75 mg twice daily would result in similar exposure for severely renally impaired patients with CRCL of 15-30 mL min(-1) and patients with normal renal function receiving 150 mg twice daily. Conclusions: The analysis provides a thorough PK characterization of dabigatran in the AF patient population from RE-LY. None of the covariates investigated, with the exception of renal function, warrants dose adjustment.
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