| 21. |
- 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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| 22. |
- Oldgren, Jonas, et al.
(författare)
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Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation
- 2016
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 134:22, s. 1697-1707
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Atrial fibrillation (AF) is associated with increased but variable risk of stroke. Our aim was to validate the recently developed biomarker-based ABC-stroke risk score and compare its performance with the CHA2DS2VASc and ATRIA risk scores.METHODS: -ABC-stroke score includes Age, Biomarkers (NT-proBNP and high-sensitivity [hs] troponin [cTn]), and Clinical history (prior stroke). This validation was based on 8,356 patients, 16,137 person-years of follow-up, and 219 adjudicated stroke or systemic embolic (SE) events in anticoagulated patients with AF in the RE-LY study. Levels of NT-proBNP, hs-cTnT, and hs-cTnI were determined in plasma samples obtained at study entry.RESULTS: -The ABC-stroke score was well calibrated with 0.76 stroke/SE events per 100 person-years in the predefined low (<1%/year) risk group, 1.48 in the medium (1-2%/year) risk group, and 2.60 in the high (>2%/year) risk group for the ABC-stroke score with hs-cTnT. Hazard ratios for stroke/SE were 1.95 for medium versus low risk, and 3.44 for high versus low risk groups. ABC-stroke score achieved C indices of 0.65 with both hs-cTnT and hs-cTnI, as compared with 0.60 for CHA2DS2VASc (p=0.004 for hs-cTnT and p=0.022 hs-cTnI) and 0.61 for ATRIA scores (p=0.005 hs-cTnT and p=0.034 for hs-cTnI).CONCLUSIONS: -The biomarker-based ABC-stroke score was well calibrated and consistently performed better than both the CHA2DS2VASc and ATRIA stroke scores. The ABC score should be considered an improved decision support tool in the care of patients with AF.
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| 23. |
- Pol, Tymon, et al.
(författare)
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Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas
- 2021
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Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions. Methods Data were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region. Results GDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (p<0.0001). Similarly, GDF-15 and the ABC-AFdeath score were associated with all-cause mortality in both trials across regions (p<0.0001). Overall, the association between GDF-15, the ABC-AF-bleeding score and ABC-AF-death risk score with major bleeding and death was consistent across regions in both ARISTOTLE and the RE-LY trial cohorts. The ABC-AF-bleeding and ABC-AF-death risk scores were consistent regarding discriminative ability when comparing geographic regions in both trial cohorts. The C-indices ranged from 0.649 to 0.760 for the ABC-AF-bleeding and from 0.677 to 0.806 for the ABC-AF-death score by different geographic regions. Conclusions In patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions.
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| 24. |
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| 25. |
- Sharma, Abhinav, et al.
(författare)
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Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation : Insights From the ARISTOTLE Trial
- 2018
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:16, s. 1666-1676
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown. Methods: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death. Results: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death. Conclusions: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.
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| 26. |
- Al-Khatib, Sana M., et al.
(författare)
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Outcomes of apixaban vs. warfarin by type and duration of atrial fibrillation : results from the ARISTOTLE trial
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:31, s. 2464-2471
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Tidskriftsartikel (refereegranskat)abstract
- It is uncertain whether the benefit from apixaban varies by type and duration of atrial fibrillation (AF). A total of 18 201 patients with AF [2786 (15.3) with paroxysmal and 15 412 (84.7) with persistent or permanent] were randomized to apixaban or warfarin. In this pre-specified secondary analysis, we compared outcomes and treatment effect of apixaban vs. warfarin by AF type and duration. The primary efficacy endpoint was a composite of ischaemic or haemorrhagic stroke or systemic embolism. The secondary efficacy endpoint was all-cause mortality. There was a consistent reduction in stroke or systemic embolism (P for interaction 0.71), all-cause mortality (P for interaction 0.75), and major bleeding (P for interaction 0.50) with apixaban compared with warfarin for both AF types. Apixaban was superior to warfarin in all studied endpoints, regardless of AF duration at study entry (P for all interactions 0.13). The rate of stroke or systemic embolism was significantly higher in patients with persistent or permanent AF than patients with paroxysmal AF (1.52 vs. 0.98; P 0.003, adjusted P 0.015). There was also a trend towards higher mortality in patients with persistent or permanent AF (3.90 vs. 2.81; P 0.0002, adjusted P 0.066). The risks of stroke, mortality, and major bleeding were lower with apixaban than warfarin regardless of AF type and duration. Although the risk of stroke or systemic embolism was lower in paroxysmal than persistent or permanent AF, apixaban is an attractive alternative to warfarin in patients with AF and at least one other risk factor for stroke, regardless of the type or duration of AF.
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| 27. |
- Alexander, John H, et al.
(författare)
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Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine : A Secondary Analysis of a Randomized Clinical Trial
- 2016
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 1:6, s. 673-681
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: In the Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) trial, the standard dose of apixaban was 5 mg twice daily; patients with at least 2 dose-reduction criteria-80 years or older, weight 60 kg or less, and creatinine level 1.5 mg/dL or higher-received a reduced dose of apixaban of 2.5 mg twice daily. Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban.OBJECTIVE: To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5 mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria.DESIGN, SETTING, AND PARTICIPANTS: Among 18 201 patients in the ARISTOTLE trial, 17 322 were included in this analysis. Annualized event rates of stroke or systemic embolism and major bleeding and hazard ratios (HRs) and 95% CIs were evaluated. Interactions between the effects of apixaban vs warfarin and the presence of 1 or no dose-reduction criteria were assessed. The first patient was enrolled in the ARISTOTLE trial on December 19, 2006, and follow-up was completed on January 30, 2011. Data were analyzed from January 2015 to May 30, 2016.MAIN OUTCOMES AND MEASURES: Analysis of major bleeding included events during study drug treatment. Analysis of stroke or systemic embolism was based on intention to treat.RESULTS: Of the patients with 1 or no dose-reduction criteria assigned to receive the 5 mg twice daily dose of apixaban or warfarin, 3966 had 1 dose-reduction criterion; these patients had higher rates of stroke or systemic embolism (HR, 1.47; 95% CI, 1.20-1.81) and major bleeding (HR, 1.89; 95% CI, 1.62-2.20) compared with those with no dose-reduction criteria (n = 13 356). The benefit of the 5 mg twice daily dose of apixaban (n = 8665) compared with warfarin (n = 8657) on stroke or systemic embolism in patients with 1 dose-reduction criterion (HR, 0.94; 95% CI, 0.66-1.32) and no dose-reduction criterion (HR, 0.77; 95% CI, 0.62-0.97) were similar (P for interaction = .36). Similarly, the benefit of 5 mg twice daily dose of apixaban compared with warfarin on major bleeding in patients with 1 dose-reduction criterion (HR, 0.68; 95% CI, 0.53-0.87) and no dose-reduction criterion (HR, 0.72; 95% CI, 0.60-0.86) were similar (P for interaction = .71). Similar patterns were seen for each dose-reduction criterion and across the spectrum of age, body weight, creatinine level, and creatinine clearance.CONCLUSIONS AND RELEVANCE: Patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5 mg twice daily dose of apixaban vs warfarin compared with patients without these characteristics. The 5 mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00412984.
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| 28. |
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| 29. |
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| 30. |
- Carnicelli, Anthony P., et al.
(författare)
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Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation : Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 145:4, s. 242-255
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Tidskriftsartikel (refereegranskat)abstract
- Background: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data.Methods: We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex.Results: A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin.Conclusions: Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.
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