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Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

ABSTRACT: INTRODUCTION:The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. METHODS:This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). RESULTS:Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+?5 U?±?24.1 vs - 6 U?±?22.2, respectively, p?=?0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p?=?0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p?=?0.026], but no significant differences were observed with dabigatran. CONCLUSIONS:DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT02389582.

SUBMITTER: Arantes FBB

PROVIDER: S-EPMC6979460 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

Arantes Flávia B B FBB Menezes Fernando R FR Franci Andre A Barbosa Carlos J D G CJDG Dalçoquio Talia F TF Nakashima Carlos A K CAK Baracioli Luciano M LM Furtado Remo H M RHM Nomelini Quintiliano S S QSS Ramires José A F JAF Kalil Filho Roberto R Nicolau José C JC

Advances in therapy 20191122 1

<h4>Introduction</h4>The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability.<h4>Methods</h4>This was a prospective, interventional study of patients with chronic coronary a ...[more]

PMID: 31758517

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Project description:BackgroundHyperglycaemia may attenuate the antiplatelet effect of aspirin and thereby increase the risk of cardiovascular events. We investigated the influence of increased haemoglobin A1c (HbA1c) levels on platelet aggregation and turnover in a large cohort of patients with coronary artery disease (CAD) with type 2 diabetes, prediabetes or no diabetes.MethodsIn this observational study, we included 865 stable CAD patients on 75 mg aspirin as mono-therapy of whom 242 patients had type 2 diabetes and were receiving antidiabetic drugs. Among 623 patients without diabetes, we classified 303 patients with prediabetes (HbA1c ≥5.7-6.4% [39-47 mmol/mol]) naive to antidiabetic drugs. Platelet aggregation was evaluated by the Multiplate Analyzer using arachidonic acid and collagen and by the VerifyNow Aspirin. Platelet turnover was evaluated by immature platelets using flow cytometry and platelet activation by soluble P-selectin.ResultsCAD patients with type 2 diabetes had higher platelet aggregation (all p-values <0.01), platelet turnover (immature platelet count, p<0.01) and platelet activation (p<0.001) than patients without diabetes. CAD patients with prediabetes had increased platelet aggregation (p = 0.02) and platelet count (p = 0.02) compared with patients without diabetes. Increased levels of HbA1c correlated positively with increased platelet aggregation using arachidonic acid (r = 0.19, p<0.0001), collagen (r = 0.10, p<0.01) and VerifyNow (r = 0.15, p<0.0001), and with platelet count (r = 0.08, p = 0.01), immature platelet count (r = 0.11, p<0.001) and soluble P-selectin (r = 0.15, p<0.0001). These associations were mainly evident in non-diabetic and prediabetic CAD patients.ConclusionsCAD patients with prediabetes and diabetes may have attenuated antiplatelet effect of aspirin compared with CAD patients without diabetes. This may be related to increased platelet count in patients with prediabetes. Increased levels of HbA1c correlated positively, though weakly, with increased platelet aggregation, platelet turnover and platelet activation.

Dataset Information

Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

Publications

Influence of Direct Thrombin Inhibitor and Low Molecular Weight Heparin on Platelet Function in Patients with Coronary Artery Disease: A Prospective Interventional Trial.

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