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- Alexander, John H., et al.
(författare)
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Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation : insights from the ARISTOTLE trial
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:4, s. 224-232
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Tidskriftsartikel (refereegranskat)abstract
- Aims We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). Methods and results In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10 vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Conclusion Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.
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| 2. |
- De Caterina, Raffaele, et al.
(författare)
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Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation : an analysis of the ARISTOTLE trial.
- 2020
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 8:3, s. 227-235
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial.METHODS AND RESULTS: Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62-2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90-1.94); for insulin-treated diabetes: 2.34 (1.43-3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86-166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88-1.42); for insulin-treated diabetes 1.85 (1.36-2.53), interaction P = 0.001.CONCLUSION: In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.
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| 3. |
- Ezekowitz, Justin A., et al.
(författare)
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Clinical outcomes of patients with diabetes and atrial fibrillation treated with apixaban : results from the ARISTOTLE trial
- 2015
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : OXFORD UNIV PRESS. - 2055-6837 .- 2055-6845. ; 1:2, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- Aims We compared clinical outcomes in patients with AF with and without diabetes in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial. Methods and results The main efficacy endpoints were SSE and mortality; safety endpoints were major and major/clinically relevant non-major bleeding. A total of 4547/18 201 (24.9%) patients had diabetes who were younger (69 vs. 70 years), more had coronary artery disease (39 vs. 31%), and higher mean CHADS(2) (2.9 vs. 1.9) and HAS-BLEDscores (1.9 vs. 1.7) (all P, 0.0001) than patients without diabetes. Patients with diabetes receiving apixaban had lower rates of SSE [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.53-1.05), all-cause mortality (HR 0.83, 95% CI 0.67-1.02), cardiovascular mortality (HR 0.89, 95% CI 0.66-1.20), intra-cranial haemorrhage (HR 0.49, 95% CI 0.25-0.95), and a similar rate of myocardial infarction (HR 1.02, 95% CI 0.62-1.67) compared with warfarin. For major bleeding, a quantitative interaction was seen (P-interaction = 0.003) with a greater reduction in major bleeding in patients without diabetes even after multivariable adjustment. Other measures of bleeding showed a consistent reduction with apixaban compared with warfarin without a significant interaction based on diabetes status. Conclusion Apixaban has similar benefits on reducing stroke, decreasing mortality, and causing less intra-cranial bleeding than warfarin in patients with and without diabetes.
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| 4. |
- Granger, Christopher B., et al.
(författare)
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Apixaban versus Warfarin in Patients with Atrial Fibrillation
- 2011
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 365:11, s. 981-992
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Tidskriftsartikel (refereegranskat)abstract
- Background Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). Conclusions In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality.
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| 5. |
- McMurray, John J. V., et al.
(författare)
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Left Ventricular Systolic Dysfunction, Heart Failure, and the Risk of Stroke and Systemic Embolism in Patients With Atrial Fibrillation Insights From the ARISTOTLE Trial
- 2013
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Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:3, s. 451-460
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Tidskriftsartikel (refereegranskat)abstract
- Background-We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. Methods and Results-The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups. Conclusions-Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups.
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