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(Circulation. 1997;96:2118-2120.)
© 1997 American Heart Association, Inc.

Articles

Direct Thrombin Inhibition Superior to Heparin During and After Thrombolysis

Dose, Duration, and Drug

James H. Chesebro, MD

From the Cardiovascular Institute, Mount Sinai Medical Center, New York, NY.

Correspondence to James H. Chesebro, MD, Cardiovascular Institute, Box 1030, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029-6574.

Key Words: Editorials • heparin • thrombolysis • thrombosis

	Introduction

 
Thrombosis and thrombolysis are dynamic, simultaneous, and opposing processes. Blocking one opposing process will enhance the other. The more potent the antithrombotic drug, the more rapid and thorough the thrombolysis.¹ Enhancing thrombolysis reduces the residual mass of mural thrombus and thus the residual stenosis, local shear force, and propensity for platelet deposition and reocclusion. The immediate increase in thrombin generation and activity with thrombolysis necessitates the simultaneous administration of an antithrombotic drug with the lytic agent to maximize the extent of thrombolysis.^{1 2}

Recombinant hirudin, a 65–amino acid peptide that nearly encircles the thrombin molecule, is the prototype and gold standard of direct thrombin inhibitors.³ It is the tightest-binding (K_i=10^-13) thrombin inhibitor and can be detected as the hirudin-thrombin complex at least 18 hours after r-hirudin administration is stopped.⁴ When administered to humans intravenously to prolong the aPTT ratio to only 1.7x to 2.2x control levels, its potency for blocking growth of thrombus on aortic tunica media during ex vivo perfusion at moderate shear force is similar in quantitative antithrombotic potency to c7E3.^4A Other direct thrombin inhibitors with lower binding affinities (K_i=10^-11 and K_i=10^-9) experimentally have proved to be less potent antithrombotics against thrombosis than r-hirudin in porcine carotid and coronary arteries after deep arterial injury by angioplasty.⁵ Two other direct anti-thrombins, Inogatran (K_i=10^-9) and Efegatran, a tripeptide (LY 294468), have low binding affinities and were clinically no better than heparin during studies in patients with unstable angina^{6 7} and acute myocardial . . . [Full Text of this Article]

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