Publications (5)148.66 Total impact
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Article: NT-proBNP for Risk Assessment in Patients with Atrial Fibrillation: Insights from the ARISTOTLE trial.
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ABSTRACT: OBJECTIVE: To assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE trial, and the treatment effect of apixaban according to NT-proBNP levels. BACKGROUND: Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. METHODS: In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. RESULTS: Quartiles of NT-proBNP were Q1:≤363, Q2:364-713, Q3:714-1250 and Q4:>1250 ng/L. During 1.8 years the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, adjusted hazard ratio (HR) 2.35 (95% CI 1.62-3.40, p<0.0001. Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, adjusted HR 2.50 (1.81-3.45), p<0.0001. Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p=0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p<0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. CONCLUSIONS: Levels of NT-proBNP are often elevated in AF and independently associated with an increased risk for stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared to warfarin is independent of the NT-proBNP level.Journal of the American College of Cardiology 04/2013; · 14.16 Impact Factor -
Article: Effi cacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fi brillation: a secondary analysis of a randomised controlled trial
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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 diff ered 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 fi brillation 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. Effi cacy 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 signifi cantly reduced stroke or systemic embolism with no evidence of a diff erential eff ect 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 diff erence 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 benefi ts over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2, CHA2DS2VASc, 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 stratifi cation for both stroke and bleeding is needed, particularly for patients with atrial fi brillation at low risk for these events.The Lancet 10/2012; · 38.28 Impact Factor -
Article: 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.
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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 CHADS2, CHA2DS2VASc, 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. FUNDING: Bristol-Myers Squibb and Pfizer.The Lancet 10/2012; · 38.28 Impact Factor -
Article: Apixaban versus warfarin in patients with atrial fibrillation.
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ABSTRACT: 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. 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. 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). In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).New England Journal of Medicine 08/2011; 365(11):981-92. · 53.30 Impact Factor -
Article: Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale.
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ABSTRACT: Atrial fibrillation (AF) is associated with increased risk of stroke that can be attenuated with vitamin K antagonists (VKAs). Vitamin K antagonist use is limited, in part, by the high incidence of complications when patients' international normalized ratios (INRs) deviate from the target range. The primary objective of ARISTOTLE is to determine if the factor Xa inhibitor, apixaban, is noninferior to warfarin at reducing the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism in patients with AF and at least 1 additional risk factor for stroke. We have randomized 18,206 patients from over 1,000 centers in 40 countries. Patients were randomly assigned in a 1:1 ratio to receive apixaban or warfarin using a double-blind, double-dummy design. International normalized ratios are monitored and warfarin (or placebo) is adjusted aiming for a target INR range of 2 to 3 using a blinded, encrypted point-of-care device. Minimum treatment is 12 months, and maximum expected exposure is 4 years. Time to accrual of at least 448 primary efficacy events will determine treatment duration. The key secondary objectives are to determine if apixaban is superior to warfarin for the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, and for all-cause death. These will be tested after the primary objective using a closed test procedure. The noninferiority boundary is 1.38; apixaban will be declared noninferior if the 95% CI excludes the possibility that the primary outcome rate with apixaban is >1.38 times higher than with warfarin. ARISTOTLE will determine whether apixaban is noninferior or superior to warfarin in preventing stroke and systemic embolism; whether apixaban has particular benefits in the warfarin-naïve population; whether it reduces the combined rate of stroke, systemic embolism, and death; and whether it impacts bleeding.American heart journal 03/2010; 159(3):331-9. · 4.65 Impact Factor
