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Wuttke, M., Li, Y., Li, M., Sieber, K. B., Feitosa, M. F., Gorski, M., . . . Pattaro, C. (2019). A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nature Genetics, 51(6), 957-972
Open this publication in new window or tab >>A catalog of genetic loci associated with kidney function from analyses of a million individuals
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 6, p. 957-972Article in journal (Refereed) Published
Abstract [en]

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-387933 (URN)10.1038/s41588-019-0407-x (DOI)000469996900008 ()31152163 (PubMedID)
Funder
AstraZenecaNovo NordiskNIH (National Institute of Health)
Note

Group Authors: Lifelines COHort Study

Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2019-06-26Bibliographically approved
Ueland, T., Åkerblom, A., Ghukasyan, T., Michelsen, A. E., Becker, R. C., Bertilsson, M., . . . Wallentin, L. (2019). Admission Levels of DKK1 (Dickkopf-1) Are Associated With Future Cardiovascular Death in Patients With Acute Coronary Syndromes. Arteriosclerosis, Thrombosis and Vascular Biology, 39(2), 294-302
Open this publication in new window or tab >>Admission Levels of DKK1 (Dickkopf-1) Are Associated With Future Cardiovascular Death in Patients With Acute Coronary Syndromes
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2019 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 2, p. 294-302Article in journal (Refereed) Published
Abstract [en]

Objective- The Wnt/wingless signaling antagonist DKK1 (dickkopf-1) regulates platelet-mediated inflammation and may contribute to plaque destabilization. We hypothesized that DKK1 would be associated with cardiovascular outcomes.

Approach and Results- We determined DKK1 levels in serum samples obtained before randomization, at discharge, and 1 and 6 months in a subset of 5165 patients with acute coronary syndromes in the PLATO trial (Platelet Inhibition and Patient Outcomes; NCT00391872). The median (interquartile range) DKK1 concentrations were 0.61 (0.20-1.27) ng/mL at baseline and increased during follow-up. The hazard ratio (95% CIs) for the composite end point (cardiovascular death, nonprocedural spontaneous myocardial infarction, or stroke) during 1 year of follow-up, per 50% increase in baseline DKK1 concentration, was 1.06 (1.02-1.10), P=0.0011, and remained significant in fully adjusted analysis with 14 conventional clinical and demographic and 6 biochemical variables, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-TnT (high-sensitivity troponin T), and GDF-15 (growth differentiation factor 15; 1.05 [1.00-1.09]; P=0.028). This association was mainly driven by the association with cardiovascular death, where a gradual increase in event rates was observed with increasing quartiles of DKK1 (2.7%, 3.0%, 4.3%, and 5.0%) and remained significant and unmodified in fully adjusted analysis (hazard ratio, 1.10 [1.04-1.17]; P=0.002). Change in DKK1 and levels at 1 month were unrelated to outcomes. A modifying effect of ticagrelor on DKK1 discharge levels was observed but not associated with prognosis.

Conclusions- In patients with acute coronary syndromes treated with dual antiplatelet treatment, admission DKK1 levels were independently associated with a composite of cardiovascular death, myocardial infarction, or stroke and with cardiovascular death alone.

Keywords
acute coronary syndrome, blood platelets, follow-up studies, humans, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-374177 (URN)10.1161/ATVBAHA.118.311042 (DOI)000478870600022 ()30580572 (PubMedID)
Available from: 2019-01-18 Created: 2019-01-18 Last updated: 2019-09-30Bibliographically approved
Patel, R. S., Schmidt, A. F., Tragante, V., McCubrey, R. O., Holmes, M. V., Howe, L. J., . . . Asselbergs, F. W. (2019). Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data. Circulation: Genomic and Precision Medicine, 12(4), Article ID e002471.
Open this publication in new window or tab >>Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data
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2019 (English)In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002471Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.

METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.

RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).

CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

Keywords
chromosome, genetic, variation, myocardial infarction, risk factor, secondary prevention
National Category
Cardiac and Cardiovascular Systems Medical Genetics
Identifiers
urn:nbn:se:uu:diva-383874 (URN)10.1161/CIRCGEN.119.002471 (DOI)000466741600005 ()30897348 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 201668EU, European Research Council, 294609EU, Horizon 2020, 01KL1802NIH (National Institute of Health)EU, Horizon 2020, 692145Wellcome trustEU, FP7, Seventh Framework Programme, 223004Forte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2019-06-14 Created: 2019-06-14 Last updated: 2019-06-14Bibliographically approved
Erlinge, D., Koul, S., Omerovic, E., Fröbert, O., Linder, R., Danielewicz, M., . . . James, S. (2019). Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction. European heart journal. Acute cardiovascular care., 8, 492-501, Article ID 2048872618805663.
Open this publication in new window or tab >>Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction
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2019 (English)In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 8, p. 492-501, article id 2048872618805663Article in journal (Refereed) Published
Abstract [en]

Background: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use.

Methods: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days.

Results: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78–1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68–1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58–1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77–1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30–5.93, p=0.82).

Conclusion: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

Keywords
Bivalirudin, heparin, non-ST-elevation myocardial infarction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-374849 (URN)10.1177/2048872618805663 (DOI)000484942800002 ()30281320 (PubMedID)
Funder
Swedish Heart Lung FoundationSwedish Research CouncilAstraZenecaSwedish Foundation for Strategic Research
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-10-15Bibliographically approved
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
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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
Stewart, R. A. H., Held, C., Krug-Gourley, S., Waterworth, D., Stebbins, A., Chiswell, K., . . . White, H. (2019). Cardiovascular and Lifestyle Risk Factors and Cognitive Function in Patients With Stable Coronary Heart Disease. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(7), Article ID e010641.
Open this publication in new window or tab >>Cardiovascular and Lifestyle Risk Factors and Cognitive Function in Patients With Stable Coronary Heart Disease
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2019 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 7, article id e010641Article in journal (Refereed) Published
Abstract [en]

Background-Vascular risk factors have been associated with differences in cognitive performance in epidemiological studies, but evidence in patients with coronary heart disease is more limited. Methods and Results-The Montreal Cognitive Assessment score obtained 3.2 +/- 0.37 years after randomization to darapladib, a reversible inhibitor of lipoprotein phospholipase A2 or placebo was evaluated for 10 634 patients with coronary heart disease from 38 countries in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. The Montreal Cognitive Assessment scores for darapladib and placebo groups were similar (mean +/- SD, 25.3 +/- 3.84 versus 25.4 +/- 3.73, respectively; P=0.27) and the adjusted odds ratio (OR) for mild cognitive impairment (Montreal Cognitive Assessment score <26) was 1.00 (95% CI, 0.93-1.09). Mild cognitive impairment was more likely with increasing age (OR, 1.33 [1.27-1.41], +5 years after 65). For other baseline clinical characteristics, the strongest independent predictors of cognitive impairment were education (<= 8 years versus college/university, OR, 2.95 [2.60-3.35]; >8 years/trade school versus college/university, OR, 1.38 [1.25-1.52] and geographic grouping). Cardiovascular risk factors independently associated with cognitive impairment were history of stroke (OR, 1.43 [1.20-1.71]); <2.5 hours of moderate or vigorous intensity exercise/week (OR, 1.19 [1.04-1.37]); high-density lipoprotein cholesterol <1.16 mmol/L (OR, 1.19 [1.04-1.37]); diabetes mellitus requiring treatment (OR, yes versus no: 1.15 [1.05-1.26]); and history of hypertension (OR, 1.12 [1.02-1.23]). Conclusions-In patients with stable coronary heart disease, cognitive performance was associated with modifiable cardiovascular risk factors, educational level, and global region, but was not influenced by darapladib.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
cognitive impairment, coronary heart disease, Montreal Cognitive Assessment, risk factor
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-394175 (URN)10.1161/JAHA.118.010641 (DOI)000484574300006 ()30897999 (PubMedID)
Available from: 2019-10-08 Created: 2019-10-08 Last updated: 2019-10-08Bibliographically approved
Sharma, A., Hagström, E., Wojdyla, D. M., Neely, M. L., Harrington, R. A., Wallentin, L., . . . Lopes, R. D. (2019). Clinical consequences of bleeding among individuals with a recent acute coronary syndrome: Insights from the APPRAISE-2 trial. American Heart Journal, 215, 106-113
Open this publication in new window or tab >>Clinical consequences of bleeding among individuals with a recent acute coronary syndrome: Insights from the APPRAISE-2 trial
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2019 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 215, p. 106-113Article in journal (Refereed) Published
Abstract [en]

Background Patients with a recent acute coronary syndrome (ACS) receiving oral antiplatelets and anticoagulants are at risk for bleeding and subsequent adverse non-bleeding-related events. Methods In this post hoc analysis, we evaluated 7,392 high-risk patients (median follow-up 241 days) with a recent ACS randomized to apixaban or placebo in APPRAISE-2. Clinical events during a 30-day period after Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding were analyzed using unadjusted and adjusted Cox proportional-hazards models. Results In total, 153 (2.1%) patients experienced TIMI major/minor bleeding during follow-up. Bleeding risk for patients on triple therapy (apixaban, thienopyridine, and aspirin) was increased compared with those on dual therapy (apixaban plus aspirin: hazard ratio [HR] 2.02, 95% CI 1.08-3.79; thienopyridine plus aspirin: HR 1.99, 95% CI 1.41-2.83). Those receiving apixaban/aspirin had similar bleeding risk compared with those receiving thienopyridine/aspirin (HR 1.01, 95% CI 0.53-1.95). Patients who experienced TIMI major/minor bleeding had an increased risk of 30-day all-cause mortality (HR 24.7, 95% CI 15.34-39.66) and ischemic events (HR 6.7, 95% CI 3.14-14.14). Conclusions In a contemporary cohort of high-risk patients after ACS, bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic or anticoagulant strategy. Patients receiving apixaban plus aspirin had a similar bleeding risk compared with those receiving thienopyridine plus aspirin. Interventions to improve outcomes in patients after ACS should include strategies to optimize the reduction in ischemic events while minimizing the risk of bleeding.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-393326 (URN)10.1016/j.ahj.2019.05.004 (DOI)000478778600013 ()31310855 (PubMedID)
Available from: 2019-09-27 Created: 2019-09-27 Last updated: 2019-09-27Bibliographically approved
Christersson, C., Wallentin, L., Andersson, U., Alexander, J. H., Alings, M., De Caterina, R., . . . Siegbahn, A. (2019). Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.. Heart, 105(3), 235-242
Open this publication in new window or tab >>Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.
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2019 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 105, no 3, p. 235-242Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).

METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.

RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.

CONCLUSIONS: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.

TRIAL REGISTRATION NUMBER: NCT00412984.

Keywords
atrial fibrillation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-374491 (URN)10.1136/heartjnl-2018-313351 (DOI)000459806200013 ()30209126 (PubMedID)
Available from: 2019-01-21 Created: 2019-01-21 Last updated: 2019-03-21Bibliographically approved
Hohnloser, S. H., Fudim, M., Alexander, J. H., Wojdyla, D. M., Ezekowitz, J. A., Hanna, M., . . . Lopes, R. D. (2019). Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight: Insights From the ARISTOTLE Trial. Circulation, 139(20), 2292-2300
Open this publication in new window or tab >>Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight: Insights From the ARISTOTLE Trial
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 20, p. 2292-2300Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Guidelines caution against the use of non-vitamin K antagonist oral anticoagulants in patients with extremely high (> 120 kg) or low (= 60 kg) body weight because of a lack of data in these populations.

METHODS: In a post hoc analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n= 18 201), a randomized trial comparing apixaban with warfarin for the prevention of stroke in patients with atrial fibrillation, we estimated the randomized treatment effect (apixaban versus warfarin) stratified by body weight (= 60, > 60-120, > 120 kg) using a Cox regression model and tested the interaction between body weight and randomized treatment. The primary efficacy and safety outcomes were stroke or systemic embolism and major bleeding.

RESULTS: Of the 18 139 patients with available weight and outcomes data, 1985 (10.9%) were in the low-weight group (= 60 kg), 15 172 (83.6%) were in the midrange weight group (> 60-120 kg), and 982 (5.4%) were in the high-weight group (> 120 kg). The treatment effect of apixaban versus warfarin for the efficacy outcomes of stroke/systemic embolism, all-cause death, or myocardial infarction was consistent across the weight spectrum (interaction P value> 0.05). For major bleeding, apixaban had a better safety profile than warfarin in all weight categories and even showed a greater relative risk reduction in patients in the low (= 60 kg; HR, 0.55; 95% CI, 0.36-0.82) and midrange (> 60-120 kg) weight groups (HR, 0.71; 95% CI, 0.61-0.83; interaction P value= 0.016).

CONCLUSIONS: Our findings provide evidence that apixaban is efficacious and safe across the spectrum of weight, including in low-(= 60 kg) and highweight patients (> 120 kg). The superiority on efficacy and safety outcomes of apixaban compared with warfarin persists across weight groups, with even greater reductions in major bleeding in patients with atrial fibrillation with low to normal weight as compared with high weight. The superiority of apixaban over warfarin in regard to efficacy and safety for stroke prevention seems to be similar in patients with atrial fibrillation across the spectrum of weight, including in low-and very high-weight patients. Thus, apixaban appears to be appropriate for patients with atrial fibrillation irrespective of body weight.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
atrial fibrillation, bleeding, non-vitamin K antagonist oral anticoagulants, stroke, warfarin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-386162 (URN)10.1161/CIRCULATIONAHA.118.037955 (DOI)000468397500007 ()30773022 (PubMedID)
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Guimaraes, P. O., Pokorney, S. D., Lopes, R. D., Wojdyla, D. M., Gersh, B. J., Giczewska, A., . . . Granger, C. B. (2019). Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: Insights from the ARISTOTLE trial. Clinical Cardiology, 42(5), 568-571
Open this publication in new window or tab >>Efficacy and safety of apixaban vs warfarin in patients with atrial fibrillation and prior bioprosthetic valve replacement or valve repair: Insights from the ARISTOTLE trial
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2019 (English)In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 5, p. 568-571Article in journal (Refereed) Published
Abstract [en]

Background

The optimal anticoagulation strategy for patients with atrial fibrillation (AF) and bioprosthetic valve (BPV) replacement or native valve repair remains uncertain.

Hypothesis

We evaluated the safety and efficacy of apixaban vs warfarin in patients with AF and a history of BPV replacement or native valve repair.

Methods

Using data from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) (n = 18 201), a randomized trial comparing apixaban with warfarin in patients with AF, we analyzed the subgroup of patients (n = 251) with prior valve surgery. We contacted sites by telephone to obtain additional data about prior valve surgery. Full data were available for 156 patients. The primary efficacy endpoint was stroke/systemic embolism. The primary safety endpoint was major bleeding. Treatment groups were compared using a Cox regression model.

Results

In ARISTOTLE, 104 (0.6%) patients had a history of BPV replacement (n = 73 [aortic], n = 26 [mitral], n = 5 [mitral and aortic]) and 52 (0.3%) had a history of valve repair (n = 50 [mitral], n = 2 [aortic]). Among patients with BPVs, 55 were randomized to apixaban and 49 to warfarin. Among those with a history of native valve repair, 32 were randomized to apixaban and 20 to warfarin. Overall clinical event rates were low, with no significant differences between apixaban and warfarin for any outcomes.

Conclusions

In patients with AF and a history of BPV replacement or repair, the safety and efficacy of apixaban compared with warfarin was consistent with results from ARISTOTLE. These data suggest that apixaban may be reasonable for patients with BPVs or prior valve repair, though future larger randomized trials are needed.

ClinicalTrials.gov

NCT00412984.

Keywords
apixaban, atrial fibrillation, bioprosthetic valves, valve repair
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-387295 (URN)10.1002/clc.23178 (DOI)000468080800011 ()30907005 (PubMedID)
Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0378-6531

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