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Imbalance between Fibrin Clot Formation and Fibrinolysis Predicts Cardiovascular Events in Patients with Stable Coronary Artery DiseaseFunding This work was supported by the Danish Agency for Science Technology and Innovation (grant no. 2101–05–0052 to S.D.K.); Novo-Nordic Foundation (grant no. NNF14OC0008817 to S.D.K.); Faculty of Health Sciences, Aarhus University, Denmark; The Danish Heart Foundation; A.P. Møller Foundation; Department of Clinical Medicine, Aarhus University; The Eva and Henry Fraenkel Foundation; The Aase and Ejnar Danielsen Foundation; The Korning Foundation; The Physician's assurance association anno 1891, and The Sophus Jacobsen and Spouse Astrid Jacobsen Foundation. The funding sources had no influence on the study design, collection, analysis or interpretation of the data, writing of the article, or the decision to submit the article for publication.
13 May 2019
21 September 2019
16 November 2019 (online)
Background Despite long-term antiplatelet therapy with aspirin, recurrent cardiovascular events remain common in patients with coronary artery disease (CAD).
Objective We aimed to determine whether fibrin network characteristics are predictive of vascular events in patients with stable CAD treated with aspirin monotherapy.
Methods We included 786 patients with angiographically documented CAD and either prior myocardial infarction, type 2 diabetes mellitus, or both. Median follow-up time was 3 years. At inclusion, fibrin clot properties were evaluated using a turbidimetric assay and the following clot parameters were studied: (1) maximum absorbance, a measure of clot density and fiber thickness; (2) lysis time, assessing fibrinolysis potential; and (3) area under the curve (AUC), a measure of clot formation and lysis. The primary endpoint was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards regression.
Results A total of 70 primary endpoints occurred. The primary endpoint occurred more frequently in CAD patients with increased clot AUC (crude HR for first vs. fourth quartile: 2.4 [95% confidence interval 1.2–4.6], p = 0.01). This finding remained significant after adjusting for potential confounders (adjusted HR: 2.4 [1.2–4.8], p = 0.01). Neither clot maximum absorbance nor lysis time showed significant association with future vascular events (adjusted HR for maximum absorbance 1.8 [0.9–3.7]; p = 0.09) and lysis time (1.6 [0.8–3.0]; p = 0.18).
Conclusion We demonstrate that increased clot AUC predicts future cardiovascular events in stable CAD patients receiving aspirin monotherapy.
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