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Ueland, T., Åkerblom, A., Ghukasyan, T., Michelsen, A. E., Becker, R. C., Bertilsson, M., . . . Wallentin, L. (2020). ALCAM predicts future cardiovascular death in acute coronary syndromes: Insights from the PLATO trial. Atherosclerosis, 293, 35-41
Open this publication in new window or tab >>ALCAM predicts future cardiovascular death in acute coronary syndromes: Insights from the PLATO trial
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2020 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 293, p. 35-41Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Activated leukocyte cell adhesion molecule (ALCAM) is upregulated during inflammation and involved in transmigration of leukocytes and T-cell activation. We hypothesized that ALCAM might be associated with recurrent events in patients with acute coronary syndromes (ACS).

METHODS: ALCAM was measured in serum obtained on admission, at discharge, 1 month and 6 months in a subgroup of 5165 patients admitted with ACS and included in the PLATelet inhibition and patient Outcomes (PLATO) trial (NCT00391872). The association between ALCAM and the composite endpoint and its components, including cardiovascular (CV) death, non-procedural spontaneous myocardial infarction (MI) or stroke during 1-year follow-up, was assessed by Cox proportional hazards models with incremental addition of clinical risk factors and biomarkers (including high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15).

RESULTS: The median (Q1-Q3) concentration of ALCAM at admission was 97 (80-116) ng/mL. A 50% higher level of ALCAM on admission was associated with a hazard ratio (HR) of 1.16 (95% confidence interval [1.00-1.34] p = 0.043) for the composite endpoint in fully adjusted analysis, mainly driven by the association with CV death (HR 1.45 [1.16-1.82] p = 0.0012).

CONCLUSIONS: In patients with ACS, admission level of ALCAM was independently associated with adverse outcome including CV death even after adjustment for established inflammatory and cardiac biomarkers.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Activated leukocyte cell adhesion molecule, Acute coronary syndromes, CV death, Prognosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-401230 (URN)10.1016/j.atherosclerosis.2019.11.031 (DOI)000506889300005 ()31835039 (PubMedID)
Funder
AstraZenecaSwedish Foundation for Strategic Research
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-02-20Bibliographically 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
Kessler, T., Wolf, B., Eriksson, N., Kofink, D., Mahmoodi, B. K., Rai, H., . . . Schunkert, H. (2019). Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention. Cardiovascular Research, 115(10), 1512-1518
Open this publication in new window or tab >>Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention
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2019 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 115, no 10, p. 1512-1518Article in journal (Refereed) Published
Abstract [en]

Aim A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. Methods and results The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU.min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203AU.min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. Conclusion We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2019
Keywords
On-aspirin platelet reactivity, Genetic variation, Stent thrombosis, Genome-wide association studies, Platelet aggregation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-397295 (URN)10.1093/cvr/cvz015 (DOI)000492854700015 ()30768153 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, HEALTH-F2-2013-601456EU, European Research Council, ERC 261053
Available from: 2019-11-25 Created: 2019-11-25 Last updated: 2019-11-25Bibliographically approved
Andersen, T., Ueland, T., Ghukasyan Lakic, T., Åkerblom, A., Bertilsson, M., Aukrust, P., . . . Kontny, F. (2019). C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes. Arteriosclerosis, Thrombosis and Vascular Biology, 39(11), 2402-2410
Open this publication in new window or tab >>C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in 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 11, p. 2402-2410Article in journal (Refereed) Published
Abstract [en]

Objective:

The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.

Approach and Results:

Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.

Conclusions:

In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.

Keywords
acute coronary syndrome, biomarkers, inflammation, risk factors
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-397674 (URN)10.1161/ATVBAHA.119.312633 (DOI)000494483700023 ()31554419 (PubMedID)
Funder
Swedish Foundation for Strategic Research
Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved
Åkerblom, A., Oldgren, J., Latva-Rasku, A., Johansson, L., Lisovskaja, V., Karlsson, C., . . . Nuutila, P. (2019). Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients - a description of the DAPACARD study. Upsala Journal of Medical Sciences, 124(1), 59-64
Open this publication in new window or tab >>Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients - a description of the DAPACARD study
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2019 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 59-64Article in journal (Refereed) Published
Abstract [en]

Background: Diabetes increases the risk for cardiovascular (CV) events. It has recently been shown that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to a reduction in CV outcomes in patients with type 2 diabetes mellitus (T2DM), including mortality and heart failure hospitalization. The exact mechanisms of how SGLT2 inhibitors lead to this CV risk reduction remain incompletely understood. The study of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency and myocardial contractile work in type 2 diabetes patients (DAPACARD) (NCT03387683) explores the possible effects of dapagliflozin, an SGLT2 inhibitor, on cardiac work, metabolism, and biomarker levels.

Methods: DAPACARD is an international, randomized, double-blind trial that aims to examine the effects of dapagliflozin versus matching placebo in 52 patients with T2DM that are on stable metformin therapy prior to and during the 6 weeks of treatment. The primary efficacy endpoint is change in global longitudinal strain of the left ventricle (GLSLV) measured with magnetic resonance imaging (MRI) between baseline (pre-treatment) and end of study (on-treatment). The secondary endpoint is the corresponding change in myocardial efficiency measured as external left ventricular work divided by total left ventricular work, which is estimated using [11C]-acetate clearance using positron emission tomography (PET).

Conclusion: The DAPACARD study is an extensive investigation of cardiac function and metabolism, by advanced imaging with PET and MRI, as well as biomarkers, performed in order to further explore how the SGLT2 inhibitor dapagliflozin could influence cardiovascular outcomes in patients with T2DM.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Diabetes, experimental diabetes, magnetic resonance, molecular biology, nuclear medicine
National Category
Endocrinology and Diabetes Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-381209 (URN)10.1080/03009734.2018.1515281 (DOI)000461811100013 ()30618324 (PubMedID)
Funder
AstraZeneca
Available from: 2019-04-09 Created: 2019-04-09 Last updated: 2019-04-09Bibliographically approved
Åkerblom, A., Wojdyla, D., Steg, P. G., Wallentin, L., James, S., Budaj, A., . . . Becker, R. C. (2019). Prevalence and relevance of abnormal glucose metabolism in acute coronary syndromes: insights from the PLATelet inhibition and patient Outcomes (PLATO) trial. Journal of Thrombosis and Thrombolysis, 48(4), 563-569
Open this publication in new window or tab >>Prevalence and relevance of abnormal glucose metabolism in acute coronary syndromes: insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
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2019 (English)In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 48, no 4, p. 563-569Article in journal (Refereed) Published
Abstract [en]

Diabetes mellitus (DM) and abnormal glucose metabolism are associated with cardiovascular (CV) disease. We investigated the prevalence and prognostic importance of dysglycaemia in patients with acute coronary syndromes (ACS) in the PLATelet inhibition and patient Outcomes (PLATO) trial. Diabetes was defined as known diabetes or HbA1c >= 6.5% or non-fasting glucose >= 11.1 mmol/L on admission, prediabetes as HbA1c >= 5.7% but < 6.5%, and no diabetes as HbA1c < 5.7%. The primary endpoint was the composite of CV death, spontaneous myocardial infarction type 1 (sMI) or stroke at 12 months. Multivariable Cox regression models, adjusting for baseline characteristics, and biomarkers NT-proBNP and troponin I, were used to explore the association between glycaemia and outcome. On admission, 16,007 (86.1%) patients had HbA1c and/or glucose levels available and were subdivided into DM 38.5% (6160) (1501 patients had no previous DM diagnosis), prediabetes 38.8% (6210), and no DM 22.7% (3637). Kaplan Meier event rates at 12 months for CV death, sMI or stroke per subgroups were 14.5% (832), 9.0% (522), and 8.5% (293), respectively with multivariable adjusted HRs, versus no diabetes, for diabetes: 1.71 (1.50-1.95) and for prediabetes 1.03 (0.90-1.19). Corresponding event rates for CV death were 6.9% (391), 3.4% (195) and 3.0% (102), respectively, with adjusted HRs for patients with DM of: 1.92 (1.42-2.60) and for prediabetes 1.02 (0.79-1.32). Abnormal glucose metabolism is common in ACS patients, but only patients with definite DM have an increased CV risk, indicating that prediabetes is not immediately associated with worse CV outcomes.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Diabetes, Pre-diabetes, Hemoglobin A1C, Acute coronary syndromes, Myocardial infarction, Risk prediction
National Category
Endocrinology and Diabetes Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-399089 (URN)10.1007/s11239-019-01938-2 (DOI)000491548800005 ()31512201 (PubMedID)
Funder
AstraZeneca
Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-16Bibliographically approved
Patel, R. S., Tragante, V., Schmidt, A. F., McCubrey, R. O., Holmes, M. V., Howe, L. J., . . . Asselbergs, F. W. (2019). Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium. Circulation: Genomic and Precision Medicine, 12(4), Article ID e002470.
Open this publication in new window or tab >>Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium
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2019 (English)In: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, no 4, article id e002470Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.

METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.

RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.

CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Keywords
coronary artery disease, genetics, myocardial infarction, prognosis, secondary prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-383875 (URN)10.1161/CIRCGEN.119.002470 (DOI)000466741600004 ()30896328 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 201668EU, FP7, Seventh Framework Programme, 305739EU, European Research Council, 294609Swedish Research CouncilSwedish Foundation for Strategic Research EU, European Research Council, 294609EU, Horizon 2020, 01KL1802NIH (National Institute of Health), R0133169NIH (National Institute of Health), R01ES021801NIH (National Institute of Health), R01MD010358NIH (National Institute of Health), R01ES025786NIH (National Institute of Health), R01HL103866NIH (National Institute of Health), R01DK106000NIH (National Institute of Health), R01HL126827NIH (National Institute of Health), P20HL113452NIH (National Institute of Health), P01HL098055NIH (National Institute of Health), P01HL076491NIH (National Institute of Health), R01HL103931NIH (National Institute of Health), AG051633NIH (National Institute of Health), 5P01HL101398-02NIH (National Institute of Health), 1P20HL113451-01NIH (National Institute of Health), 1R56HL126558-01NIH (National Institute of Health), 1RF-1AG051633-01NIH (National Institute of Health), R01 NS064162-01NIH (National Institute of Health), R01 HL89650-01NIH (National Institute of Health), HL095479-01NIH (National Institute of Health), 1U10HL110302-01NIH (National Institute of Health), 1DP3DK094346-01NIH (National Institute of Health), 2P01HL086773-06A1EU, Horizon 2020, 692145Wellcome trust, 072960/Z/03/ZWellcome trust, 084726/Z/08/ZWellcome trust, 084727/Z/08/ZWellcome trust, 085475/Z/08/ZWellcome trust, 085475/B/08/ZSwedish Heart Lung FoundationThe Crafoord FoundationKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework Programme, 223004Forte, Swedish Research Council for Health, Working Life and WelfareNIH (National Institute of Health), R01 NR013396
Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-06-12Bibliographically approved
Åkerblom, A., Wojdyla, D. M., Wallentin, L., James, S., Brito, F. d., Steg, P. G., . . . Lopes, R. D. (2019). Ticagrelor in patients with heart failure after acute coronary syndromes - Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial. American Heart Journal, 213, 57-65
Open this publication in new window or tab >>Ticagrelor in patients with heart failure after acute coronary syndromes - Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
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2019 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 213, p. 57-65Article in journal (Refereed) Published
Abstract [en]

Background: Heart failure (HF) following acute coronary syndromes (ACS) is associated with worse prognosis; however, the efficacy and safety of ticagrelor in patients with HF and if ticagrelor influences the risk of new-onset HF are unknown.

Methods: We examined the efficacy and safety of ticagrelor compared to clopidogrel in patients with ACS in the randomized PLATelet inhibition and patient Outcomes (PLATO) trial subdivided by strata: (1) previous HF and/or clinical signs of HF on admission or (2) no HF on admission. The primary outcome was the combination of cardiovascular death, myocardial infarction, or stroke evaluated by multivariable Cox regression models. The safety outcome was major bleeding. New-onset HF was defined as an HF event after discharge in patients without previous HF.

Results: Data were available in 18,556 patients, whom 2,862 (15.4%) patients had HF, including 1,584 (8.5%) patients with previous HF. Patients randomized to ticagrelor had lower risk of the composite end point regardless of HF status: hazard ratio (HR) 0.87 (95% CI: 0.73-1.03) in patients with HF and HR 0.84 (95% CI: 0.75-0.93) in patients with no HF (P = .76). Corresponding HR for major bleeding were HR 1.08 (95% CI: 0.87-1.34) and HR 1.03 (95% CI: 0.94-1.14) (P = .71). There was no difference in new-onset HF at 12 months between patients randomized to ticagrelor (4.1%, n = 278) or clopidogrel (4.0%, n = 276).

Conclusions: In patients with ACS, ticagrelor is more efficacious in protecting against new ischemic events and mortality than clopidogrel irrespective of the presence of HF. There is no difference between ticagrelor or clopidogrel treatment in new-onset HF post-ACS.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-390088 (URN)10.1016/j.ahj.2019.04.006 (DOI)000471598600007 ()31108273 (PubMedID)
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-08-05Bibliographically approved
Szummer, K., Lindhagen, L., Evans, M., Spaak, J., Koul, S., Åkerblom, A., . . . Jernberg, T. (2019). Treatments and Mortality Trends in Cases With and Without Dialysis Who Have an Acute Myocardial Infarction: An 18-Year Nationwide Experience. Circulation. Cardiovascular Quality and Outcomes, 12(9)
Open this publication in new window or tab >>Treatments and Mortality Trends in Cases With and Without Dialysis Who Have an Acute Myocardial Infarction: An 18-Year Nationwide Experience
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2019 (English)In: Circulation. Cardiovascular Quality and Outcomes, ISSN 1941-7713, E-ISSN 1941-7705, Vol. 12, no 9Article in journal (Refereed) Published
Abstract [en]

Background: Patients on dialysis who have an acute myocardial infarction (AMI) have an exceedingly poor prognosis, but it is unknown to what extent guideline-recommended interventions and treatments are used and to which benefit. We aimed to assess temporal changes in the use of treatments and survival rates in dialysis patients with an AMI.

Methods and Results: All consecutive AMI cases from 1996 to 2013 enrolled in the SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) were included. The Swedish Renal Registry identified all chronic dialysis cases. Multivariable adjusted standardized 1-year mortality was estimated. An age-sex-calendar year-matched dialysis background population from the Swedish Renal Registry was used to obtain a standardized incidence ratio. All analyses were performed in 2-year blocks, where each individual could be included several times but in different time blocks; hence the term AMI cases and not patients is used. Of 289 699 cases with AMI, 1398 (0.5%) were on dialysis (73.6% hemodialysis; 26.4% peritoneal dialysis). Among dialysis cases, 29.4% were women, and 21.0% had ST-segment-elevation myocardial infarction. Through 1996 to 2013, dialysis cases had similar age (median, 70 years [interquartile range, 62-77]; P for trend, 0.14), but the proportion with diabetes mellitus increased (36.0%-55.3%; P for trend, 0.005). Dialysis cases admitted with AMI were treated more invasively and received more discharge medications in the later years. From 1995 to 2013, in-hospital and 1-year mortality decreased from 25.4% to 9.4% and from 59.6% to 41.2%, respectively. The standardized in-hospital and 1-year mortality decreased from 25.7% to 9.4% and from 54.6% to 41.2%. Yet, compared with the matched dialysis population, the odds of death remained as high in 2012/2013 as in 1996/1997 (odds ratio, 2.04; 95% CI, 1.62-2.58 and odds ratio, 1.99; 95% CI, 1.52-2.60, respectively; P for trend, 0.34).

Conclusions: Over the last 18 years, more patients on dialysis with AMI have been treated with evidence-based therapies. Overall, dialysis cases with AMI have an improved in-hospital and 1-year survival in the more recent years compared with earlier years. However, this appears largely to be because of improved survival in the general dialysis population.

Keywords
dialysis, humans, myocardial infarction, registries, renal insufficiency, chronic
National Category
Cardiac and Cardiovascular Systems Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-399020 (URN)10.1161/CIRCOUTCOMES.119.005879 (DOI)000486227100009 ()31510770 (PubMedID)
Funder
Swedish Foundation for Strategic Research Swedish Heart Lung FoundationThe Karolinska Institutet's Research Foundation
Available from: 2019-12-16 Created: 2019-12-16 Last updated: 2019-12-16Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0458-2736

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