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

Flávia B B Arantes, Fernando R Menezes, Andre Franci, Carlos J D G Barbosa, Talia F Dalçoquio, Carlos A K Nakashima, Luciano M Baracioli, Remo H M Furtado, Quintiliano S S Nomelini, José A F Ramires, Roberto Kalil Filho, José C Nicolau, Flávia B B Arantes, Fernando R Menezes, Andre Franci, Carlos J D G Barbosa, Talia F Dalçoquio, Carlos A K Nakashima, Luciano M Baracioli, Remo H M Furtado, Quintiliano S S Nomelini, José A F Ramires, Roberto Kalil Filho, José C Nicolau

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.

Keywords: Anti-Xa; Aspirin; Coronary artery disease; Direct thrombin inhibitor; Platelet aggregability.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Enrollment and treatment
Fig. 3
Fig. 3
Platelet aggregation and activation differences from baseline for dabigatran and enoxaparin
Fig. 4
Fig. 4
Individual platelet aggregation changes from baseline when compared to dabigatran and to enoxaparin. a Thromboxane B2 test comparing median; b MEA-ASPI test comparing means

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Source: PubMed

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