Alternative parenteral anticoagulation with argatroban, a direct thrombin inhibitor

Abstract

Argatroban, a direct thrombin inhibitor, effectively inhibits free and clot-bound thrombin without the need of a cofactor and exerts dose-dependent anticoagulant effects that are rapidly active and rapidly reversible (elimination half-life: 39-51 min). Argatroban provides predictable parenteral anticoagulation and is well tolerated with an acceptably low bleeding risk in a variety of clinical settings, including heparin-induced thrombocytopenia, acute ischemic stroke, percutaneous coronary intervention and hemodialysis. This review will discuss the clinical pharmacology and utility of argatroban; in particular, clinical trial experiences will be discussed in patients with, or at risk of, heparin-induced thrombocytopenia (where heparins must be avoided) including those requiring hemodialysis or percutaneous coronary intervention, and in patients with acute ischemic stroke (where heparins are not generally recommended).

Treatment for Patients with Acute Ischemic Stroke Presenting beyond Six Hours of Ischemic Symptom Onset : Effectiveness of Intravenous Direct Thrombin Inhibitor, Argatroban

“…This drug reversibly bind the catalytic site of thrombin and does not require other cofactors, and its anticoagulation effect is achieved after IV administration. Argatroban has the potential to reduce secondary microthrombin in the penumbra, improve regional blood flow, reduce ischemic lesions and ameliorate neurological deficits via the inhibition of circulating and clot-bound thrombin, platelet aggregation, and vascular contraction 3,13,14,24) . The nationale for the early administration of antithrombotic drugs is to prevent propagation of an acute thrombosis and recurrent embolism 23) .…”

“…The initial stroke severity was analyzed by dividing the three categories according to the baseline NIHSS score as mild (0-6); moderate (7)(8)(9)(10)(11)(12)(13)(14)(15); severe (beyond 16) 1,21) . As a result, mild stroke was diagnosed in 44 patients (55%), moderate stroke in 32 (40%), and severe stroke in four (5%).…”

“…There was no death of patient involved in this study. The median NIHSS was 8.0 (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] at admission, 4.1 (range, 0-18) upon discharge, and 3.3 (range, 0-17) after three months. A good outcome was achieved in 65 patients (81%) upon discharge and in 71 patients (88%) after three months.…”

“…Argatroban is a selective direct thrombin inhibitor that has recently been used in the treatment of AIS and it has been approved in Japan and Korea as a treatment option for non-lacunar subtype-AIS presenting within 48 hours of ischemic symptom onset 3,14) . Argatroban has the potential to reduce secondary microthrombin in the penumbra, improve regional blood flow, reduce ischemic lesions and ameliorate neurological deficits 3,13,14,24) .…”

“…Argatroban has the potential to reduce secondary microthrombin in the penumbra, improve regional blood flow, reduce ischemic lesions and ameliorate neurological deficits 3,13,14,24) . It has been shown in many previous clinical and animal studies that this drug is effective for AIS patients without increasing intracranial hemorrhage 3,9,[11][12][13][14][15][16]24) . In this study, we performed IV argatroban in patients with AIS presenting beyond six hours of ischemic symptom onset in order to analyze the efficacy and safety of this drug.…”