| 1. |
- Lopes, Renato D., et al.
(författare)
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Digoxin and Mortality in Patients With Atrial Fibrillation
- 2018
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 71:10, s. 1063-1074
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Digoxin is widely used in patients with atrial fibrillation (AF). OBJECTIVES The goal of this paper was to explore whether digoxin use was independently associated with increased mortality in patients with AF and if the association was modified by heart failure and/or serum digoxin concentration.METHODS: The association between digoxin use and mortality was assessed in 17,897 patients by using a propensity score-adjusted analysis and in new digoxin users during the trial versus propensity score-matched control participants. The authors investigated the independent association between serum digoxin concentration and mortality after multivariable adjustment.RESULTS: At baseline, 5,824 (32.5%) patients were receiving digoxin. Baseline digoxin use was not associated with an increased risk of death (adjusted hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 0.96 to 1.23; p = 0.19). However, patients with a serum digoxin concentration $ 1.2 ng/ml had a 56% increased hazard of mortality (adjusted HR: 1.56; 95% CI: 1.20 to 2.04) compared with those not on digoxin. When analyzed as a continuous variable, serum digoxin concentration was associated with a 19% higher adjusted hazard of death for each 0.5-ng/ml increase (p = 0.0010); these results were similar for patients with and without heart failure. Compared with propensity score-matched control participants, the risk of death (adjusted HR: 1.78; 95% CI: 1.37 to 2.31) and sudden death (adjusted HR: 2.14; 95% CI: 1.11 to 4.12) was significantly higher in new digoxin users.CONCLUSIONS: In patients with AF taking digoxin, the risk of death was independently related to serum digoxin concentration and was highest in patients with concentrations $ 1.2 ng/ml. Initiating digoxin was independently associated with higher mortality in patients with AF, regardless of heart failure.
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| 2. |
- Dalgaard, Frederik, et al.
(författare)
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Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial
- 2020
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 141:1, s. 10-20
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Tidskriftsartikel (refereegranskat)abstract
- Background:The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin.Methods:The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models.Results:Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11–2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16–2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.Conclusions:A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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| 3. |
- De Caterina, Raffaele, et al.
(författare)
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History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial
- 2016
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 175, s. 175-183
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Tidskriftsartikel (refereegranskat)abstract
- Aims History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. Methods and results The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. Conclusion In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.
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| 4. |
- Lopes, Renato D., et al.
(författare)
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Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation : a secondary analysis of a randomised controlled trial
- 2012
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9855, s. 1749-1758
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Tidskriftsartikel (refereegranskat)abstract
- Background The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism, causes less bleeding, and results in lower mortality. We assessed in this trial's participants how results differed according to patients' CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, used to predict the risk of stroke and bleeding. Methods ARISTOTLE was a double-blind, randomised trial that enrolled 18 201 patients with atrial fibrillation in 39 countries. Patients were randomly assigned apixaban 5 mg twice daily (n=9120) or warfarin (target international normalised ratio 2.0-3.0; n=9081). The primary endpoint was stroke or systemic embolism. The primary safety outcome was major bleeding. We calculated CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores of patients at randomisation. Efficacy analyses were by intention to treat, and safety analyses were of the population who received the study drug. ARISTOTLE is registered with ClinicalTrials.gov, number NCT00412984. Findings Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke (CHADS(2) 1, 2, or >= 3, p for interaction=0.4457; or CHA(2)DS(2)VASc 1, 2, or >= 3, p for interaction=0.1210) or bleeding (HAS-BLED 0-1, 2, or >= 3, p for interaction=0.9422). Patients who received apixaban had lower rates of major bleeding than did those who received warfarin, with no difference across all score categories (CHADS(2), p for interaction=0.4018; CHA(2)DS(2)VASc, p for interaction=0.2059; HAS-BLED, p for interaction=0.7127). The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher (hazard ratio [HR] 0.22, 95% CI 0.10-0.48) than in those with HAS-BLED scores of 0-1 (HR 0.66, 0.39-1.12; p for interaction=0.0604). Interpretation Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS(2), CHA(2)DS(2)VASc, and HAS-BLED scores, these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin. Further improvement in risk stratification for both stroke and bleeding is needed, particularly for patients with atrial fibrillation at low risk for these events.
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| 5. |
- Wallentin, Lars, et al.
(författare)
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Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 127:22, s. 2166-2176
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR).Methods and ResultsThe trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53–1.00) and 0.88 (95% CI, 0.57–1.35) (Pinteraction=0.078), for mortality were 0.91 (95% CI, 0.74–1.13) and 0.91 (95% CI, 0.71–1.16) (Pinteraction=0.34), and for major bleeding were 0.50 (95% CI, 0.36–0.70) and 0.75 (95% CI, 0.58–0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR.ConclusionsThe benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers’ and patients’ predicted quality of international normalized ratio control.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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