| 1. |
- Guimaraes, Patricia O., et al.
(författare)
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Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation : Insights from the ARISTOTLE trial
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 227, s. 443-449
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Methods: Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30 days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. Results: In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed Al' had a similar risk of stroke/systemic embolism (HR = 1.07, 95% CI = 0.80-1.42; p 0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR = 1.21, 95% Cl 1.02-1.43; p 0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AI' diagnosis (all interaction p-values >0.12). Conclusion: Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis.
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| 2. |
- Guimarães, Patrícia O, et al.
(författare)
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Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation : a Meta-Analysis Based on Imputed Placebo Effect
- 2017
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Ingår i: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 31:3, s. 295-301
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting.METHODS: To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment.RESULTS: In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6-52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18-47%; p = 0.0002).CONCLUSIONS: In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo.
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| 3. |
- Guimaraes, Patricia O., et al.
(författare)
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International normalized ratio control and subsequent clinical outcomes in patients with atrial fibrillation using warfarin
- 2019
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 48:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- We explored associations between INR measures and clinical outcomes in patients with AF using warfarin, and whether INR history predicted future INR measurements. We included patients in ARISTOTLE who were randomized to and received warfarin. Among patients who had events, we included those with ≥ 3 INR values in the 180 days prior to the event, with the most recent ≤ 60 days prior to the event, who were on warfarin at the time of event (n = 545). Non-event patients were included in the control group if they had ≥ 180 days of warfarin exposure with ≥ 3 INR measurements (n = 7259). The median (25th, 75th) number of INR values per patient was 29 (21, 38) over a median follow-up of 1.8 years. A total of 87% had at least one INR value < 1.5; 49% had at least one value > 4.0. The last INRs before events (median 14 [24, 7] days) were < 3.0 for at least 75% of patients with major bleeding and > 2.0 for half of patients with ischemic stroke. Historic time in therapeutic range (TTR) was weakly associated with future TTR (R2 = 0.212). Historic TTR ≥ 80% had limited predictive ability to discriminate future TTR ≥ 80% (C index 0.61). In patients with AF receiving warfarin, most bleeding events may not have been preventable despite careful INR control. Our findings suggest that INRs collected through routine management are not sufficiently predictive to provide reassurance about future time in therapeutic range or to prevent subsequent outcomes, and might be over-interpreted in clinical practice.
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| 4. |
- 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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