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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
Garcia, D. A., Fisher, D. A., Mulder, H., Wruck, L., De Caterina, R., Halvorsen, S., . . . Lopes, R. D. (2020). Gastrointestinal bleeding in patients with atrial fibrillation treated with Apixaban or warfarin: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. American Heart Journal, 221, 1-8
Open this publication in new window or tab >>Gastrointestinal bleeding in patients with atrial fibrillation treated with Apixaban or warfarin: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial
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2020 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 221, p. 1-8Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: A history of gastrointestinal bleeding (GIB) in patients with atrial fibrillation (AF) may impact decisions about anticoagulation treatment. We sought to determine whether prior GIB in patients with AF taking anticoagulants was associated with an increased risk of stroke or major hemorrhage.

METHODS: We analyzed key efficacy and safety outcomes in patients with prior GIB in ARISTOTLE. Centrally adjudicated outcomes according to GIB history were analyzed using Cox proportional hazards models adjusted for randomized treatment and established risk factors.

RESULTS: A total of 784 (4.3%) patients had prior GIB events (321 [41%] lower, 463 [59%] upper); 215 (27%) occurred <1 year before study enrollment. Patients with prior GIB were older, had more comorbidities, and higher CHADS2 and HAS-BLED scores than those with no GIB. Major GIB occurred more frequently in those with prior GIB (lower: aHR 1.72, 95% CI 0.86-3.42; upper: aHR 3.13, 95% CI 1.97-4.96). This association with major GIB was more pronounced in patients with GIB <1 year before randomization versus no recent GIB (recent lower: aHR 2.58, 95% CI 0.95-7.01; recent upper: aHR 5.16, 95% CI 2.66-10.0). There was no association between prior GIB and risk of stroke/systemic embolism or all-cause death. In those with prior GIB, the apixaban versus warfarin relative risks for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding were consistent with the results of the overall trial.

CONCLUSIONS: In patients with AF on oral anticoagulants, prior GIB was associated with an increased risk of subsequent major GIB but not stroke, intracranial bleeding, or all-cause mortality. For the key outcomes of stroke, hemorrhagic stroke, death, and major bleeding, we found no evidence that the treatment effect (apixaban vs. warfarin) was modified by a history of GIB.

Place, publisher, year, edition, pages
Elsevier, 2020
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-401291 (URN)10.1016/j.ahj.2019.10.013 (DOI)000512980500001 ()31896036 (PubMedID)
Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2020-03-26Bibliographically approved
Dalgaard, F., Mulder, H., Wojdyla, D. M., Lopes, R. D., Held, C., Alexander, J. H., . . . Al-Khatib, S. M. (2020). Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial. Circulation, 141(1), 10-20
Open this publication in new window or tab >>Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial
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2020 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 1, p. 10-20Article in journal (Refereed) Published
Abstract [en]

Background:

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin.

Methods:

The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models.

Results:

Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11–2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16–2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.

Conclusions:

A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.

Clinical Trial Registration:

URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Keywords
anticoagulant drugs, atrial fibrillation, bleeding, NSAIDs, warfarin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-403393 (URN)10.1161/CIRCULATIONAHA.119.041296 (DOI)000505803800004 ()31747786 (PubMedID)
Available from: 2020-01-29 Created: 2020-01-29 Last updated: 2020-01-29Bibliographically approved
Bahit, M. C., Granger, C. B., Alexander, J. H., Mulder, H., Wojdyla, D. M., Hanna, M., . . . Lopes, R. D. (2020). Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial. International Journal of Cardiology, 302, 53-58
Open this publication in new window or tab >>Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial
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2020 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 302, p. 53-58Article in journal (Refereed) Published
Abstract [en]

Background: Variation in patient characteristics and practice patterns may influence outcomes at a regional level.

Methods: We assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding.

Results: Compared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking >= 9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0-3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with war-farin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03).

Conclusions: Patients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific. 

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD, 2020
Keywords
Region, Clinical outcomes, Atrial fibrillation, Apixaban, Warfarin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-406503 (URN)10.1016/j.ijcard.2019.12.060 (DOI)000510846300013 ()31932116 (PubMedID)
Available from: 2020-03-10 Created: 2020-03-10 Last updated: 2020-03-10Bibliographically approved
Simonsson, M., Wallentin, L., Alfredsson, J., Erlinge, D., Hellström Ängerud, K., Hofmann, R., . . . Jernberg, T. (2020). Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry. European Heart Journal, 41(7), 833-843
Open this publication in new window or tab >>Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry
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2020 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 41, no 7, p. 833-843Article in journal (Refereed) Published
Abstract [en]

AIMS: To describe the time trends of in-hospital and out-of-hospital bleeding parallel to the development of new treatments and ischaemic outcomes over the last 20 years in a nationwide myocardial infarction (MI) population.

METHODS AND RESULTS: Patients with acute MI (n = 371 431) enrolled in the SWEDEHEART registry from 1995 until May 2018 were selected and evaluated for in-hospital bleeding and out-of-hospital bleeding events at 1 year. In-hospital bleeding increased from 0.5% to a peak at 2% 2005/2006 and thereafter slightly decreased to a new plateau around 1.3% by the end of the study period. Out-of-hospital bleeding increased in a stepwise fashion from 2.5% to 3.5 % in the middle of the study period and to 4.8% at the end of the study period. The increase in both in-hospital and out-of-hospital bleeding was parallel to increasing use of invasive strategy and adjunctive antithrombotic treatment, dual antiplatelet therapy (DAPT), and potent DAPT, while the decrease in in-hospital bleeding from 2007 to 2010 was parallel to implementation of bleeding avoidance strategies. In-hospital re-infarction decreased from 2.8% to 0.6% and out-of-hospital MI decreased from 12.6% to 7.1%. The composite out-of-hospital MI, cardiovascular death, and stroke decreased in a similar fashion from 18.4% to 9.1%.

CONCLUSION: During the last 20 years, the introduction of invasive and more intense antithrombotic treatment has been associated with an increase in bleeding events but concomitant there has been a substantial greater reduction of ischaemic events including improved survival.

Keywords
Acute myocardial infarction, Bleeding, Registry, Temporal trends
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-401634 (URN)10.1093/eurheartj/ehz593 (DOI)000515104400008 ()31504404 (PubMedID)
Funder
Swedish Heart Lung FoundationStockholm County Council
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2020-04-02Bibliographically approved
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
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
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
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-0378-6531

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