| 1. |
- Alexander, Karen P, et al.
(författare)
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Outcomes of apixaban versus warfarin in patients with atrial fibrillation and multi-morbidity : Insights from the ARISTOTLE trial
- 2019
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 208, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with atrial fibrillation (AF) often have multi-morbidity, defined as ≥3 comorbid conditions. Multi-morbidity is associated with polypharmacy, adverse events, and frailty potentially altering response to anticoagulation. We sought to describe the prevalence of multi-morbidity among older patients with AF and determine the association between multi-morbidity, clinical outcomes, and the efficacy and safety of apixaban compared with warfarin.METHODS: In this post-hoc subgroup analysis of the ARISTOTLE trial, we studied enrolled patients age ≥ 55 years (n = 16,800). Patients were categorized by the number of comorbid conditions at baseline: no multi-morbidity (0-2 comorbid conditions), moderate multi-morbidity (3-5 comorbid conditions), and high multi-morbidity (≥6 comorbid conditions). Association between multi-morbidity and clinical outcomes were analyzed by treatment with a median follow-up of 1.8 (1.3-2.3) years.RESULTS: Multi-morbidity was present in 64% (n = 10,713) of patients; 51% (n = 8491) had moderate multi-morbidity, 13% (n = 2222) had high multi-morbidity, and 36% (n = 6087) had no multi-morbidity. Compared with the no multi-morbidity group, the high multi-morbidity group was older (74 vs 69 years), took twice as many medications (10 vs 5), and had higher CHA2DS2-VASc scores (4.9 vs 2.7) (all P < .001). Adjusted rates per 100 patient-years for stroke/systemic embolism, death, and major bleeding increased with multi-morbidity (Reference no multi-morbidity; moderate multi-morbidity 1.42 [1.24-1.64] and high multi-morbidity 1.92 [1.59-2.31]), with no interaction in relation to efficacy or safety of apixaban.CONCLUSIONS: Multi-morbidity is prevalent among the population with AF; efficacy and safety of apixaban is preserved in this subgroup supporting extension of trial results to the most complex AF patients.
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| 2. |
- Aulin, Julia, et al.
(författare)
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Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model
- 2022
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 251, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAtrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.MethodsThe study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.ResultsBaseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P < .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.ConclusionsIn anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.
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| 3. |
- Aulin, Julia, et al.
(författare)
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Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation
- 2015
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 170:6, s. 1151-1160
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Tidskriftsartikel (refereegranskat)abstract
- Background Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. Methods Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. Results Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism (P =.0041), major bleedings (P =.0001), vascular death (P<.0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) (P<.0001). CRP was independently related to myocardial infarction (P =.0047), vascular death (P =.0004), and the composite thromboembolic outcome (P =.0001). When further adjusted for cardiac (troponin andN-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death (P<.0001), major bleeding (P<.0170) and the composite thromboembolic outcome (P<.0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 (P =.0017) when adding IL-6 to the clinically used CHA(2)DS(2)-VASc risk score with net reclassification improvement of 28%. Conclusion In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction.
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| 4. |
- Hijazi, Ziad, et al.
(författare)
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Efficacy and safety of dabigatran compared with warfarin in patients with atrial fibrillation in relation to renal function over time-A RE-LY trial analysis
- 2018
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 198, s. 169-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renal function may decline over time, and the efficacy and safety of dabigatran in atrial fibrillation (AF) in relation to renal function changes are unknown.& para;& para;Methods: The RE-LY trial randomized 18,113 patients with AF to 2 doses of dabigatran or warfarin for stroke prevention. Serial creatinine measurements were available in 16,988 patients. The relations between treatment, outcomes, and renal function (Cockcroft-Gault) were investigated using Cox-regression (1) with renal function as a time-dependent covariate and (2) according to worsening renal function (WRF) during follow-up, predefined as a decline in estimated glomerular filtration rate >20% from baseline.& para;& para;Results: During a median follow-up of 1.8 years, 4,106 (24.2%) participants were observed to have WRF, and 12,882 (75.8%) had stable renal function. The risks of all-cause mortality and major bleeding were higher in patients with WRF versus those with stable renal function (hazard ratio [95% CI]: 2.17 [1.81-2.59] and 1.43 [1.19-1.71]. respectively; both P < .0005). The efficacy and safety of dabigatran versus warfarin were similar irrespective of renal function changes over time (interaction P values >= .13 in both models). Dabigatran 110 mg showed a greater relative risk reduction of major bleeding in patients with normal renal function (estimated glomerular filtration rate >80 mL/min) during follow-up (interaction P= .026).& para;& para;Conclusions: In AF, WRF was associated with a higher risk of death and major bleeding. The efficacy and safety profile of dabigatran compared with warfarin was similar irrespective of renal function changes over time. Dabigatran 110 mg showed a greater relative risk reduction of major bleeding in patients with normal renal function during follow-up.
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| 5. |
- Hijazi, Ziad, et al.
(författare)
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Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation : Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial
- 2017
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 190, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial.METHODS: GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment.RESULTS: GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores.CONCLUSIONS: In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment.
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| 6. |
- Hijazi, Ziad, et al.
(författare)
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Individual net clinical outcome with oral anticoagulation in atrial fibrillation using the ABC-AF risk scores
- 2023
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 261, s. 55-63
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDecisions on stroke prevention strategies in patients with atrial fibrillation (AF) depend on the perceived risks of stroke and bleeding with different antithrombotic treatment strategies. The study objectives were to evaluate net clinical outcome with oral anticoagulation (OAC) for the individual patient with AF and to identify clinically relevant thresholds for OAC treatment.MethodsPatients with AF receiving OAC treatment in the randomized ARISTOTLE and RE-LY trials, with available biomarkers for calculation of ABC-AF scores at baseline, were included (n = 23,121). Observed 1-year risk on OAC was compared with predicted 1-year risk if the same patients would not have received OAC using the ABC-AF scores calibrated for aspirin. Net clinical outcome was defined as the sum of stroke and major bleeding risks.ResultsThe ratio between the 1-year incidence of major bleeding and stroke/systemic embolism events ranged from 1.4 to 10.6 according to different ABC-AF risk profiles. Net clinical outcome analyses showed that in patients with an ABC-AF-stroke risk >1% per year on OAC (>3% without OAC), treatment with OAC consistently provides larger net clinical benefit than no-OAC treatment. In patients with an ABC-AF-stroke risk <1.0% per year on OAC (<3% without OAC) an individualized balancing of risks regarding OAC or no-OAC treatment is needed.ConclusionsIn patients with AF, the ABC-AF risk scores allow an individual and continuous estimate of the balance between benefits and risks with OAC treatment. This precision medicine tool therefore seems useful as decision support and visualizes the net clinical benefit or harm with OAC treatment (http://www.abc-score.com/abcaf/).Clinical Trial RegistrationClinicalTrials.gov identifier NCT00412984 (ARISTOTLE) and NCT00262600 (RE-LY).
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| 7. |
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| 8. |
- Tomasdottir, Maria, et al.
(författare)
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Risk markers of incident atrial fibrillation in patients with coronary heart disease
- 2021
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 233, s. 92-101
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn patients with coronary heart disease (CHD), atrial fibrillation (AF) is associated with increased morbidity and mortality. We investigated the associations between clinical risk factors and biomarkers with incident AF in patients with CHD.Methods and resultsAround 13,153 patients with optimally treated CHD included in the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial with plasma samples obtained at randomization. Mean follow-up time was 3.5 years. The association between clinical risk factors and biomarkers with incident AF was estimated with Cox-regression models. Validation was performed in 1,894 patients with non-ST-elevation acute coronary syndrome included in the FRISC-II trial.The median (min-max) age was 64 years (range 26-92) and 2,514 (19.1%) were women. A total of 541 patients, annual incidence rate of 1.2%, developed AF during follow-up. In multivariable models, older age, higher levels of NT-proBNP, higher body mass index (BMI), male sex, geographic regions, low physical activity, and heart failure were independently associated with increased risk of incident AF with hazard ratios ranging from 1.04 to 1.79 (P ≤ .05). NT-proBNP improved the C-index from 0.70 to 0.71. In the validation cohort, age, BMI, and NT-proBNP were associated with increased risk of incident AF with similar hazard ratios.ConclusionsIn patients with optimally treated CHD, the incidence of new AF was 1.2% per year. Age, NT-proBNP as a marker of impaired cardiac function, and BMI were the strongest factors, independently and consistently associated with incident AF. Male sex and low physical activity may also contribute to the risk of AF in patients with CHD.
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| 9. |
- Vinereanu, Dragos, et al.
(författare)
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Heart rate and death and hospitalization for heart failure in patients with persistent or permanent atrial fibrillation : Insights from the ARISTOTLE trial
- 2023
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 265, s. 132-136
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Tidskriftsartikel (refereegranskat)abstract
- Rate control is fundamental in the treatment of patients with atrial fibrillation (AF). The independent association of heart rate with outcomes and range of heart rate associated with best outcomes remains uncertain. We assessed the relationship between heart rate and clinical outcomes in patients with persistent or permanent AF enrolled in the randomized, double-blind ARISTOTLE trial. In patients with persistent or permanent AF, a faster heart rate is associated with a modest, but statistically significant increase in death and heart failure hospitalizations.
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