uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Andersson, Ulrika
Publications (10 of 32) Show all publications
Hijazi, Z., Verdecchia, P., Oldgren, J., Andersson, U., Reboldi, G., Di Pasquale, G., . . . Wallentin, L. (2019). Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE-LY Trial. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(2), Article ID e010107.
Open this publication in new window or tab >>Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE-LY Trial
Show others...
2019 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 2, article id e010107Article in journal (Refereed) Published
Abstract [en]

Background

Cardiac biomarkers and left ventricular hypertrophy (LVH) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes.

Methods and Results

Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE‐LY (Randomized Evaluation of Long‐Term Anticoagulation Therapy) trial. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor‐15 were determined using high‐sensitivity (hs) assays. LVH was defined by ECG. Cox models were adjusted for baseline characteristics, LVH, and biomarkers. LVH was present in 1257 patients. During a median follow‐up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly (P<0.0001) associated with higher levels of all biomarkers in linear regression analyses adjusting for baseline characteristics. Geometric mean ratios (95% CIs) were as follows: NT‐proBNP, 1.32 (1.25–1.38); hs cardiac troponin I, 1.67 (1.57–1.78); hs troponin T, 1.38 (1.32–1.44); and growth differentiation factor‐15, 1.09 (1.05–1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT‐proBNP, 1.09 (1.00–1.19); hs cardiac troponin I, 1.09 (1.03–1.15); hs troponin T, 1.14 (1.06–1.24); and growth differentiation factor‐15, 1.22 (1.08–1.38) (all P<0.05). For death, hazard ratios (95% CIs) were as follows: NT‐proBNP, 1.24 (1.17–1.31); hs cardiac troponin I, 1.13 (1.10–1.17); hs troponin T, 1.28 (1.23–1.34); and growth differentiation factor‐15, 1.31 (1.22–1.42) (all P<0.0001). LVH was not significantly associated with stroke or death after adjustment for biomarkers.

Conclusions

Cardiac biomarkers are significantly associated with LVH. The prognostic value of biomarkers for stroke and death is not affected by LVH. The prognostic information of LVH is attenuated in the presence of cardiac biomarkers.

Keywords
atrial fibrillation, biomarker, left ventricular hypertrophy, risk prediction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-379402 (URN)10.1161/JAHA.118.010107 (DOI)000460105800004 ()30651032 (PubMedID)
Available from: 2019-03-15 Created: 2019-03-15 Last updated: 2019-03-15Bibliographically approved
Horowitz, J. D., De Caterina, R., Heresztyn, T., Alexander, J. H., Andersson, U., Lopes, R. D., . . . Wallentin, L. (2018). Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation: An ARISTOTLE Substudy. Journal of the American College of Cardiology, 72(7), 721-733
Open this publication in new window or tab >>Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation: An ARISTOTLE Substudy
Show others...
2018 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 72, no 7, p. 721-733Article in journal (Refereed) Published
Abstract [en]

BACKGROUND There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. OBJECTIVES The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. METHODS Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. RESULTS Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients' age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p < 0.001) with both increased CHA2DS2-VASc and HAS-BLED scores, but decreased in the presence of diabetes. On multivariable analysis adjusting for established risk factors and treatment, tertile groups of ADMA concentrations were significantly associated with stroke/systemic embolism (p = 0.034), and death (p < 0.0001), whereas tertile groups of SDMA were associated with major bleeding and death (p < 0.001 for both). Incorporating ADMA and SDMA into CHA2DS2-VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither ADMA nor SDMA predicted differential responses to warfarin or apixaban. CONCLUSIONS In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984)

Keywords
ADMA, atrial fibrillation, cerebral infarction, nitric oxide, SDMA
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-363109 (URN)10.1016/j.jacc.2018.05.058 (DOI)000440783900003 ()30092948 (PubMedID)
Funder
AstraZeneca
Available from: 2018-10-15 Created: 2018-10-15 Last updated: 2018-10-15Bibliographically approved
Proietti, M., Hijazi, Z., Andersson, U., Connolly, S. J., Eikelboom, J. W., Ezekowitz, M. D., . . . Wallentin, L. (2018). Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE-LY trial. Journal of Internal Medicine, 283(3), 282-292
Open this publication in new window or tab >>Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE-LY trial
Show others...
2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 3, p. 282-292Article in journal (Refereed) Published
Abstract [en]

Background: Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives: To compare the performance of contemporary clinical bleeding risk scores in 18113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE-LY trial.

Methods: HAS-BLED, ORBIT, ATRIA and HEMORR(2)HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results: There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P<0.001). The ORBIT score showed the best discrimination with c-indices of 0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial bleeding, which were significantly better than for the HAS-BLED score (difference in c-indices: 0.050, 0.053 and 0.048, respectively, all P<0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P=0.0019), ATRIA (P<0.001) and HEMORR(2)HAGES (P<0.001) scores. HAS-BLED score showed a nonsignificant trend for interaction (P=0.0607).

Conclusions: Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
anticoagulation treatment, atrial fibrillation, bleeding risk scores, dabigatran, major bleeding
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-347538 (URN)10.1111/joim.12702 (DOI)000425521000005 ()29044861 (PubMedID)
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved
Hijazi, Z., Hohnloser, S. H., Oldgren, J., Andersson, U., Connolly, S. J., Eikelboom, J. W., . . . Wallentin, L. (2018). 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. American Heart Journal, 198, 169-177
Open this publication in new window or tab >>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
Show others...
2018 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 198, p. 169-177Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-352697 (URN)10.1016/j.ahj.2017.10.015 (DOI)000430004300023 ()29653640 (PubMedID)
Funder
AstraZeneca
Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically approved
Sharma, A., Hijazi, Z., Andersson, U., Al-Khatib, S. M., Lopes, R. D., Alexander, J. H., . . . Wallentin, L. (2018). Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial. Circulation, 138(16), 1666-1676
Open this publication in new window or tab >>Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial
Show others...
2018 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 16, p. 1666-1676Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
Keywords
atrial fibrillation, biomarkers, cause of death, prediction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-369101 (URN)10.1161/CIRCULATIONAHA.118.034125 (DOI)000447334200009 ()29871978 (PubMedID)
Available from: 2018-12-17 Created: 2018-12-17 Last updated: 2018-12-17Bibliographically approved
Hijazi, Z., Oldgren, J., Andersson, U., Connolly, S. J., Eikelboom, J. W., Ezekowitz, M. D., . . . Wallentin, L. (2017). 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. American Heart Journal, 190, 94-103, Article ID S0002-8703(17)30172-2.
Open this publication in new window or tab >>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
Show others...
2017 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 190, p. 94-103, article id S0002-8703(17)30172-2Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342941 (URN)10.1016/j.ahj.2017.06.001 (DOI)000407410800012 ()28760218 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-03-22Bibliographically approved
Hijazi, Z., Lindahl, B., Oldgren, J., Andersson, U., Lindbäck, J., Granger, C. B., . . . Wallentin, L. (2017). Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 6(6), Article ID e004851.
Open this publication in new window or tab >>Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time
Show others...
2017 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 6, article id e004851Article in journal (Refereed) Published
Abstract [en]

Background: Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate.

Methods and Results: According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes.

Conclusions: In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months.

Clinical Trial Registration --URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
atrial fibrillation, cardiac biomarkers, natriuretic peptide, risk score, stroke, troponin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-330752 (URN)10.1161/JAHA.116.004851 (DOI)000404098700009 ()
Funder
Swedish Foundation for Strategic Research
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2017-11-29Bibliographically approved
Alexander, J. H., Andersson, U., Lopes, R. D., Hijazi, Z., Hohnloser, S. H., Ezekowitz, J. A., . . . Wallentin, L. (2016). 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. JAMA cardiology, 1(6), 673-681
Open this publication in new window or tab >>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
Show others...
2016 (English)In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 1, no 6, p. 673-681Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-304097 (URN)10.1001/jamacardio.2016.1829 (DOI)000401836900012 ()27463942 (PubMedID)
Available from: 2016-10-02 Created: 2016-10-02 Last updated: 2017-10-17Bibliographically approved
Hijazi, Z., Aulin, J., Andersson, U., Alexander, J. H., Gersh, B., Granger, C. B., . . . Wallentin, L. (2016). Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. Heart, 102(7), 508-517
Open this publication in new window or tab >>Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation
Show others...
2016 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 7, p. 508-517Article in journal (Refereed) Published
Abstract [en]

Objective: Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

Methods: The ARISTOTLE trial randomised 18 201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14 954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).

Results: The IL-6 median level was 2.3 ng/L (IQR 1.5-3.9), median CRP level was 2.2 mg/L (1.0-4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).

Conclusions: In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-293014 (URN)10.1136/heartjnl-2015-308887 (DOI)000373308500006 ()26839066 (PubMedID)
Available from: 2016-05-12 Created: 2016-05-11 Last updated: 2017-11-30Bibliographically approved
Hijazi, Z., Verdecchia, P., Oldgren, J., Andersson, U., Reboldi, M. G., Di Pasquale, G., . . . Wallentin, L. (2016). Cardiac biomarkers and left ventricular hypertrophy in relation to outcomes in patients with atrial fibrillation: experiences from the RELY trial. Paper presented at Congress of the European-Society-of-Cardiology (ESC), AUG 27-31, 2016, Rome, ITALY. EUROPEAN HEART JOURNAL, 37, 47-47
Open this publication in new window or tab >>Cardiac biomarkers and left ventricular hypertrophy in relation to outcomes in patients with atrial fibrillation: experiences from the RELY trial
Show others...
2016 (English)In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 47-47Article in journal, Meeting abstract (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-313864 (URN)000383869500146 ()
Conference
Congress of the European-Society-of-Cardiology (ESC), AUG 27-31, 2016, Rome, ITALY
Available from: 2017-01-26 Created: 2017-01-25 Last updated: 2017-01-26Bibliographically approved
Organisations

Search in DiVA

Show all publications