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Review
. 2015;7(3):191-7.

Oral direct thrombin inhibition: a double-edged sword?

Gabriele Fragasso  1 , Angelo Corti  2 , Ferdinando Loiacono  1 , Alberto Margonato  1 , Armando D'Angelo  3
Affiliations
Review

Oral direct thrombin inhibition: a double-edged sword?

Gabriele Fragasso et al. Heart Lung Vessel. 2015.

Abstract

New oral anticoagulants have been shown to be not inferior to vitamin K antagonists in reducing thrombo-embolic events in patients with non-valvular atrial fibrillation and venous thrombo-embolism. However, those among them whichdirectly inhibit thrombin have been associated with greater risk of myocardial infarction. In this article we review the pleiotropic physiological effects of thrombin and their potential link with the observed greater incidence of myocardial infarction during therapy with oral direct thrombin inhibitors. On this basis, we believe that further studies are necessary to clear out doubts on the use of these drugs in the general population and, more specifically, in patients with coronary artery disease. For these reasons, in our opinion at present it may be prudent to especially caution high risk patients initiating therapy with a direct thrombin inhibitor (or those who are already taking it) about this possible risk. For patients with established coronary artery disease an alternative oral anticoagulant may be at present a better choice.

Keywords: coronary artery disease; myocardial infarction; new oral anticoagulants; oral direct thrombin inhibition; side effects.

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Conflict of interest statement

Disclosures Gabriele Fragasso has received compensations for sponsored lectures by Servier International and Boehringer Ingelheim. Alberto Margonato has received sponsored lectures and consultancies for Astra, Boehringer Ingelheim, Bayer, DOC, Covidien and Pfizer/Bristol-Myers Squibb. Armando D'Angelo has received speaker's fees from Boehringer Ingelheim, Bayer and Bristol-Myers Squibb.

Figures

Figure 1
Figure 1
Schematic representation of thrombin pleiotropic activities. FP = fibrinopeptides; PAI = plasminogen-activator inhibitor; PAR = protease-activated receptor; PC = protein C; TAFI = thrombin-activatable fibrinolysis inhibitor;  t-PA = tissue-plasminogen activator; VWF = von Willebrand factor.
Figure 2
Figure 2
Hemostasis cascade. Straight lines mean activation, dashed lines mean inactivation. Circles outline anticoagulants principal targets. Xa: unfractioned heparin, low-molecular-weight heparin, fondaparinux, warfarin and vitamin K antagonists, rivaroxaban,apixaban, edoxaban. Thrombin: unfractioned heparin, low-molecular-weight heparin (marginally), warfarin and vitamin K antagonists, dabigatran, ximelagatran, AZD0837. HMWK = high-molecular-weight kininogen; TFPI = tissue factor pathway inhibitor.
See this image and copyright information in PMC

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