CC BY 4.0 · Thromb Haemost 2020; 120(03): 412-422
DOI: 10.1055/s-0039-1701011
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Impaired Fibrinolysis Predicts Adverse Outcome in Acute Coronary Syndrome Patients with Diabetes: A PLATO Sub-Study

Wael Sumaya
1  Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
,
Lars Wallentin
2  Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
3  Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
,
Stefan K. James
2  Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden
3  Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
,
Agneta Siegbahn
3  Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
4  Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden
,
Katja Gabrysch
3  Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
,
Anders Himmelmann
5  AstraZeneca Research and Development, Gothenburg, Sweden
,
Ramzi A. Ajjan*
6  Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
,
Robert F. Storey*
1  Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom
› Author Affiliations
Funding The present analysis was funded by the British Heart Foundation (FS/15/82/31824 clinical research training fellowship for W.S.). The PLATO trial, including plasma sample storage, was supported by AstraZeneca.
Further Information

Publication History

28 August 2019

06 December 2019

Publication Date:
23 January 2020 (online)

  

Abstract

Hypofibrinolysis is a key abnormality in diabetes but the role of impaired clot lysis in predicting vascular events and mortality in this population is yet to be determined. We aimed to investigate the relationship between fibrin clot properties and clinical outcomes in patients with diabetes and recent acute coronary syndrome (ACS). Plasma samples were collected at hospital discharge from 974 ACS patients with diabetes randomised to clopidogrel or ticagrelor in the PLATO trial. A validated turbidimetric assay was employed to study fibrin clot lysis and maximum turbidity. One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were determined using Cox proportional analysis. After adjusting for CV risk factors, each 50% increase in lysis time was associated with increased risk of CV death/MI (HR 1.21; 95% confidence interval [CI] 1.02–1.44; p = 0.026) and CV death alone (HR 1.38; 1.08–1.76; p = 0.01). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death/MI (HR 1.25; 1.02–1.53; p = 0.031) and CV death alone (HR 1.49; 1.08–2.04; p = 0.014). The relationship between lysis time and the combined outcome of CV death and MI remained significant after adjusting for multiple prognostic vascular biomarkers (p = 0.034). Neither lysis time nor maximum turbidity was associated with major bleeding events. Impaired fibrin clot lysis predicts 1-year CV death and MI in diabetes patients following ACS.

Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier NCT00391872.

* Indicates joint senior authorship.