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Wallentin, Lars
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Publications (10 of 602) Show all publications
Hijazi, Z., Oldgren, J., Lindbäck, J., Alexander, J. H., Connolly, S. J., Eikelboom, J. W., . . . Wallentin, L. (2018). A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. European Heart Journal, 39(6), 477-485
Open this publication in new window or tab >>A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 6, p. 477-485Article in journal (Refereed) Published
Abstract [en]

Aims: In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers.

Methods and results: The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score.

Conclusion: A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
Atrial fibrillation, Biomarkers, Mortality, NOAC, Oral anticoagulation, Risk score
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-348121 (URN)10.1093/eurheartj/ehx584 (DOI)000424876100015 ()29069359 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RB13-0197Swedish Heart Lung Foundation, 20090183
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-04-11Bibliographically approved
Batra, G., Friberg, L., Erlinge, D., James, S. K., Jernberg, T., Svennblad, B., . . . Oldgren, J. (2018). Antithrombotic therapy after myocardial infarction in patients with atrial fibrillation undergoing percutaneous coronary intervention. European Heart Journal - Cardiovascular Pharmacotherapy, 4(1), 36-45
Open this publication in new window or tab >>Antithrombotic therapy after myocardial infarction in patients with atrial fibrillation undergoing percutaneous coronary intervention
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2018 (English)In: European Heart Journal - Cardiovascular Pharmacotherapy, ISSN 2055-6837, E-ISSN 2055-6845, Vol. 4, no 1, p. 36-45Article in journal (Refereed) Published
Abstract [en]

Aims: Optimal antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI) and atrial fibrillation is uncertain. In this study, we compared antithrombotic regimes with regard to a composite cardiovascular outcome of all-cause mortality, MI or ischaemic stroke, and major bleeds.

Methods and results: Patients between October 2005 and December 2012 were identified in Swedish registries, n = 7116. Landmark 0-90 and 91-365 days of outcome were evaluated with Cox-regressions, with dual antiplatelet therapy as reference. At discharge, 16.2% received triple therapy (aspirin, clopidogrel, and warfarin), 1.9% aspirin plus warfarin, 7.3% clopidogrel plus warfarin, and 60.8% dual antiplatelets. For cardiovascular outcome, adjusted hazard ratio with 95% confidence interval (HR) for triple therapy was 0.86 (0.70-1.07) for 0-90 days and 0.78 (0.58-1.05) for 91-365 days. A HR of 2.16 (1.48-3.13) and 1.61 (0.98-2.66) during 0-90 and 91-365 days, respectively, was observed for major bleeds. For aspirin plus warfarin, HR 0.82 (0.54-1.26) and 0.62 (0.48-0.79) was observed for cardiovascular outcome and 1.30 (0.60-2.85) and 1.01 (0.63-1.62) for major bleeds during 0-90 and 91-365 days, respectively. For clopidogrel plus warfarin, HR of 0.90 (0.68-1.19) and 0.68 (0.49-0.95) was observed for cardiovascular outcome and 1.28 (0.71-2.32) and 1.08 (0.57-2.04) for major bleeds during 0-90 and 91-365 days, respectively.

Conclusion: Compared to dual antiplatelets, aspirin or clopidogrel plus warfarin therapy was associated with similar 0-90 days and lower 91-365 days of risk of the cardiovascular outcome, without higher risk of major bleeds. Triple therapy was associated with non-significant lower risk of cardiovascular outcome and higher risk of major bleeds.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-320310 (URN)10.1093/ehjcvp/pvx033 (DOI)000419693700010 ()29126156 (PubMedID)
Funder
Swedish Foundation for Strategic Research , KF10-0024
Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2018-02-20Bibliographically approved
Rocca, B., Fox, K. A. A., Ajjan, R. A., Andreotti, F., Baigent, C., Collet, J.-P., . . . Storey, R. F. (2018). Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis. European Heart Journal, 39(19), 1672-1686
Open this publication in new window or tab >>Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 19, p. 1672-1686Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357008 (URN)10.1093/eurheartj/ehy066 (DOI)000432687200007 ()29509886 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Goto, S., Merrill, P., Wallentin, L., Wojdyla, D. M., Hanna, M., Avezum, A., . . . Alexander, J. H. (2018). Antithrombotic therapy use and clinical outcomes following thrombo-embolic events in patients with atrial fibrillation: insights from ARISTOTLE. European Heart Journal - Cardiovascular Pharmacotherapy, 4(2), 75-81
Open this publication in new window or tab >>Antithrombotic therapy use and clinical outcomes following thrombo-embolic events in patients with atrial fibrillation: insights from ARISTOTLE
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2018 (English)In: European Heart Journal - Cardiovascular Pharmacotherapy, ISSN 2055-6837, E-ISSN 2055-6845, Vol. 4, no 2, p. 75-81Article in journal (Refereed) Published
Abstract [en]

Aims We investigated baseline characteristics, antithrombotic use, and clinical outcomes of patients with atrial fibrillation (AF) and a thrombo-embolic event in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study to better inform the care of these high-risk patients. Method and results Thrombo-embolic events were defined as stroke (ischaemic or unknown cause) or systemic embolism (SE). Clinical outcomes were estimated using the Kaplan-Meier method. All-cause mortality and International Society on Thrombosis and Haemostasis (ISTH) major bleeding after events were analysed using a Cox proportional hazards model with time-dependent covariates. Of 18 201 patients in ARISTOTLE, 365 experienced a thrombo-embolic event [337 strokes (ischaemic or unknown cause), 28 SE]; 46 (12.6%) of which were fatal. In the 30 days before and after a thrombo-embolic event, 11% and 37% of patients, respectively, were not taking an oral anticoagulant. During follow-up (median 1.8 years), 22 patients (7.1%/year) had a recurrent stroke, 97 (30.1%/year) died, and 10 (6.7%/year) had major bleeding. Compared with patients without a thrombo-embolic event, the short-and long-term adjusted hazards of death in patients with a thrombo-embolic event were high [<= 30 days: hazard ratio (HR) 54.3%, 95% confidence interval (95% CI) 41.4-71.3; >30 days: HR 3.5, 95% CI 2.5-4.8; both P<0.001]. The adjusted hazards of major bleeding were also high short-term (HR 10.37, 95% CI 3.87-27.78; P<0.001) but not long-term (HR 1.7, 95% CI: 0.77-3.88; P=0.18). Conclusions Thrombo-embolic events were rare but associated with high short-and long-term morbidity and mortality. Substantial numbers of patients are not receiving oral anticoagulattherapy before and, despite this risk, after a first thrombo-embolic event.

Keywords
Antithrombotic therapy, Thrombo-embolic events, Atrial fibrillation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-351634 (URN)10.1093/ehjcvp/pvy002 (DOI)000428883400005 ()29385429 (PubMedID)
Available from: 2018-06-07 Created: 2018-06-07 Last updated: 2018-06-07Bibliographically approved
Sherwood, M. W., Lopes, R. D., Sun, J. L., Liaw, D., Harrington, R. A., Wallentin, L., . . . Alexander, J. H. (2018). Apixaban following acute coronary syndromes in patients with prior stroke: Insights from the APPRAISE-2 trial. American Heart Journal, 197, 1-8
Open this publication in new window or tab >>Apixaban following acute coronary syndromes in patients with prior stroke: Insights from the APPRAISE-2 trial
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2018 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 197, p. 1-8Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: Patients with prior stroke are at greater risk for recurrent cardiovascular events post-acute coronary syndromes (ACS) and may have a different risk/benefit profile with antithrombotic therapy than patients without prior stroke.

METHODS: We studied 7391 patients with ACS from APPRAISE-2, stratified by the presence or absence of prior stroke. Baseline characteristics and outcomes of cardiovascular death, myocardial infarction (MI), or stroke were compared between groups. Interactions between prior stroke, treatment assignment (apixaban vs placebo), and outcomes were tested before and after multivariable adjustment with Cox proportional hazards models.

RESULTS: A total of 902 patients (12%) had prior stroke. Those with prior stroke were older (69 vs 67 years), had more hypertension (91% vs 77%), peripheral vascular disease (22% vs18%), and impaired renal function (38% vs 30%) but less diabetes (44% vs 48%) than those without prior stroke. Patients with prior stroke vs no prior stroke had higher unadjusted rates of cardiovascular death (4.8% vs 4.0%), MI (11.2% vs 7.1%), and ischemic stroke (3.2% vs 0.9%). Patients with prior stroke assigned to apixaban had similar rates of the composite of cardiovascular death, MI, or stroke compared with those assigned to placebo (HR 1.39; 95% CI 0.92-2.08). Patients without prior stroke assigned to apixaban had similar rates of cardiovascular death, MI, or ischemic stroke compared with those assigned to placebo (HR 0.87; 95% CI 0.73-1.04; P-interaction=.041). Median follow-up was 240 days.

CONCLUSIONS: Patients with prior stroke are at higher risk for recurrent cardiovascular events post-ACS and had a differential risk/benefit profile with oral anticoagulation.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342516 (URN)10.1016/j.ahj.2017.09.020 (DOI)000425723700001 ()29447769 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2018-05-03Bibliographically 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
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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
Guimarães, P. O., Leonardi, S., Huang, Z., Wallentin, L., de Werf, F. V., Aylward, P. E., . . . Tricoci, P. (2018). Clinical features and outcomes of patients with type 2 myocardial infarction: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial. American Heart Journal, 196, 28-35
Open this publication in new window or tab >>Clinical features and outcomes of patients with type 2 myocardial infarction: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial
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2018 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 196, p. 28-35Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Type 2 myocardial infarction (MI) is characterized by an imbalance between myocardial blood supply and demand, leading to myocardial ischemia without coronary plaque rupture, but its diagnosis is challenging.

METHODS: In the TRACER trial, patients with non-ST-segment elevation acute coronary syndromes were included. We aimed to describe provoking factors, cardiac biomarker profiles, treatment patterns, and clinical outcomes of patients with type 2 MIs. MI events during trial follow-up were adjudicated by an independent clinical events classification committee (CEC) and were classified according to the Third Universal Definition of MI. Using available source documents retrieved as part of the CEC process, we performed a retrospective chart abstraction to collect details on the type 2 MIs. Cox regression models were used to explore the association between MI type (type 1 or type 2) and cardiovascular death.

RESULTS: Overall, 10.3% (n=1327) of TRACER participants had a total of 1579 adjudicated MIs during a median follow-up of 502 days (25th and 75th percentiles [IQR] 349-667). Of all MIs, 5.2% (n=82) were CEC-adjudicated type 2 MIs, occurring in 76 patients. The incidence of type 2 MI was higher in the first month following randomization, after which the distribution became more scattered. The most frequent potential provoking factors for type 2 MIs were tachyarrhythmias (38.2%), anemia/bleeding (21.1%), hypotension/shock (14.5%), and hypertensive emergencies (11.8%). Overall, 36.3% had a troponin increase >10× the upper limit of normal. Coronary angiography was performed in 22.4% (n=17) of patients during hospitalizations due to type 2 MIs. The hazard of cardiovascular death was numerically higher following type 2 MI (vs. no MI, adj. HR 11.82, 95% CI 5.71-24.46; P<.0001) than that of type 1 MI (vs. no MI, adj. HR 8.90, 95% CI 6.93-11.43; P<.0001).

CONCLUSIONS: Type 2 MIs were more prevalent in the first month after ACS, were characterized by the presence of triggers and infrequent use of an invasive strategy, and were associated with a high risk of death. Further efforts are needed to better define the role and implications of type 2 MI in both clinical practice and research.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342889 (URN)10.1016/j.ahj.2017.10.007 (DOI)000424518000005 ()29421012 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-03-08Bibliographically approved
Rao, M. P., Vinereanu, D., Wojdyla, D. M., Alexander, J. H., Atar, D., Hylek, E. M., . . . Granger, C. B. (2018). Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial. American Journal of Medicine, 131(3), 269-275.e2
Open this publication in new window or tab >>Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial
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2018 (English)In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 131, no 3, p. 269-275.e2Article in journal (Refereed) Published
Abstract [en]

PURPOSE: We assessed outcomes among anticoagulated patients with atrial fibrillation and a history of falling, and whether the benefits of apixaban vs warfarin are consistent in this population.

METHODS: Of the 18,201 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, 16,491 had information about history of falling-753 with history of falling and 15,738 without history of falling. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding.

RESULTS: -VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism, Vascular disease, Age 65-74 years, Sex category female) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol) scores. Patients with a history of falling had higher rates of major bleeding (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.05-1.84; P = .020), including intracranial bleeding (adjusted HR 1.87; 95% CI, 1.02-3.43; P = .044) and death (adjusted HR 1.70; 95% CI, 1.36-2.14; P < .0001), but similar rates of stroke or systemic embolism and hemorrhagic stroke. There was no evidence of a differential effect of apixaban compared with warfarin on any outcome, regardless of history of falling. Among those with a history of falling, subdural bleeding occurred in 5 of 367 patients treated with warfarin and 0 of 386 treated with apixaban.

CONCLUSIONS: Patients with atrial fibrillation and a history of falling receiving anticoagulation have a higher risk of major bleeding, including intracranial, and death. The efficacy and safety of apixaban compared with warfarin were consistent, irrespective of history of falling.

Keywords
Anticoagulation, Apixaban, Atrial fibrillation, Bleeding, History of falls, Stroke, Warfarin
National Category
General Practice Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342519 (URN)10.1016/j.amjmed.2017.10.036 (DOI)000425092300038 ()29122636 (PubMedID)
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2018-03-08Bibliographically 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
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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
Kent, A. P., Brueckmann, M., Fraessdorf, M., Connolly, S. J., Yusuf, S., Eikelboom, J. W., . . . Ezekowitz, M. D. (2018). Concomitant Oral Anticoagulant and Nonsteroidal Anti-Inflammatory Drug Therapy in Patients With Atrial Fibrillation. Journal of the American College of Cardiology, 72(3), 255-267
Open this publication in new window or tab >>Concomitant Oral Anticoagulant and Nonsteroidal Anti-Inflammatory Drug Therapy in Patients With Atrial Fibrillation
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2018 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 72, no 3, p. 255-267Article in journal (Refereed) Published
Abstract [en]

BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used medications that can potentially increase the risk of bleeding and thrombosis. OBJECTIVES This study quantified the effect of NSAIDs in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial. METHODS This was a post hoc analysis of NSAIDs in the RE-LY study, which compared dabigatran etexilate (DE) 150 and 110 mg twice daily (b.i.d.) with warfarin in patients with atrial fibrillation. Treatment-independent, multivariate-adjusted Cox regression analysis assessed clinical outcomes by comparing NSAID use with no NSAID use. Interaction analysis was obtained from treatment-dependent Cox regression modeling. Time-varying covariate analysis for NSAID use was applied to the Cox model. RESULTS Among 18,113 patients in the RE-LY study, 2,279 patients used NSAIDs at least once during the trial. Major bleeding was significantly elevated with NSAID use (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.40 to 2.02; p < 0.0001). NSAID use did not significantly alter the risk of major bleeding for DE 150 or 110 mg b.i.d. relative to warfarin (pinteraction = 0.63 and 0.93, respectively). Gastrointestinal major bleeding was significantly elevated with NSAID use (HR: 1.81; 95% CI: 1.35 to 2.43; p < 0.0001). The rate of stroke or systemic embolism (stroke/SE) with NSAID use was significantly elevated (HR: 1.50; 95% CI: 1.12 to 2.01; p = 0.007). The use of NSAIDs did not significantly alter the relative efficacy on stroke/SE for DE 150 or 110 mg b.i.d. relative to warfarin (p(interaction) = 0.59 and 0.54, respectively). Myocardial infarction rates were similar with NSAID use compared with no NSAID use (HR: 1.22; 95% CI: 0.77 to 1.93; p = 0.40). Patients were more frequently hospitalized if they used an NSAID (HR: 1.64; 95% CI: 1.51 to 1.77; p < 0.0001). CONCLUSIONS The use of NSAIDs was associated with increased risk of major bleeding, stroke/SE, and hospitalization. The safety and efficacy of DE 150 and 110 mg b.i.d. relative to warfarin were not altered. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY]; NCT00262600)

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
Keywords
anticoagulation, atrial fibrillation, bleeding, NSAID, stroke prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-361266 (URN)10.1016/j.jacc.2018.04.063 (DOI)000438182700003 ()30012318 (PubMedID)
Funder
AstraZeneca
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-10-05Bibliographically approved
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