Different Classes of Anticoagulant Drugs in Clinical Use. Is there a Class Effect?

Abstract

Hippocrates first proposed ‘Blood thinners’ in ancient Greek medicine. Historically, extracts from many plants, bloodletting, leech bleeding, acid fruits and clear wines were considered as anticoagulants. Although, Haycraft in 1884 identified the anticoagulant in the saliva of European medicinal leech, later named hirudin, the extract was found to be too toxic. Following Jay McLean’s discovery of an anticoagulant in 1916, and naming of this anticoagulant as ‘heparin’ by Howel and Holt in 1918 and Howel’s purification of this compound in 1925, it was only in 1930s that the effective anticoagulant treatment started. Soon after the discovery of the first oral anticoagulant, dicoumarin in 1935, the purified injectable preparations of heparin were used. Later, other types of antithrombotic and anticoagulant treatment, including antiplatelet drugs, snake venoms, direct and indirect thrombin inhibitors, activated protein C, direct Factor Xa inhibitors and recombinant hirudins have since been introduced [1]. Warfarin, a conventionally used oral anticoagulant, despite its limitations of drugfood, drug-drug interactions, need for frequent PT/INR monitoring, adverse drug reactions, bleeding, warfarin-induced skin necrosis, frequent need for dosage adjustments because of changes in the dietary patterns, effects due to VKORC polymorphism, has stood the test of time and still continues to be used in clinical practice. Recently the New Oral Anticoagulant drugs, direct Factor Xa such as Rivaroxaban, Apixaban and Edoxaban and direct thrombin inhibitors such as Dabigatran were approved by the USFDA. There are several limitations in the use of NOACs such as the lack of an effective test to monitor their anticoagulant activities, the lack of an effective antidote, and dose adjustments in patients with renal impairment [2]. Thus, a bewildering wide array of anticoagulant drugs are now available for use and it is interesting to see whether or not these drugs representing different classes of anticoagulant drugs, especially direct thrombin and direct Factor Xa inhibitors have any class effects in terms of differences in their clinical outcomes.