Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range

Abstract

The optimal therapeutic range for oral anticoagulant therapy was reviewed by the Committee on Antithrombotic Therapy of the American College of Chest Physicians (ACCP) and the National Heart, Lung and Blood Institute (NHLBI) in 1986 and again in 1989. 1 ACCP/NHLBI National conference on antithrombotic therapy. Chest 1989; 89(suppl): 1-169 Google Scholar At that time, a recommendation was made that the intensity of warfarin treatment should be reduced for many indications. 1 ACCP/NHLBI National conference on antithrombotic therapy. Chest 1989; 89(suppl): 1-169 Google Scholar Since then, new clinical trials have been published which support these recommendations, and the optimal therapeutic range for many indications has been clarified. Nevertheless, the control of oral anticoagulant therapy remains a subject of confusion. The confusion persists for two related reasons. The first is the marked variation in the responsiveness of different commercial thromboplastin reagents to reductions by warfarin of vitamin K dependent clotting factors 2 Zucker S Cathey MH Sox PJ et al. Standardisation of laboratory tests for controlling anticoagulant therapy. Am J Clin Pathol. 1970; 53: 348-354 Crossref PubMed Scopus (30) Google Scholar , 3 Poller L Progress in standardisation in anticoagulant control. Hematol Rev. 1987; 1: 225-241 Google Scholar , 4 Bailey EL Harper TA Pinkerton PH Therapeutic range of one-stage prothrombin time in control of anticoagulant therapy. Can Med Assoc J. 1971; 105: 1041-1043 PubMed Google Scholar , 5 Latallo ZS Thomson JM Poller L An evaluation of chromogenic substrates in the control of oral anticoagulant therapy. Br J Haematol. 1981; 47: 307-318 Crossref PubMed Scopus (21) Google Scholar , 6 Poller L Taberner DA Dosage and control of oral anticoagulants: an international survey. Br J Haematol. 1982; 51: 479-485 Crossref PubMed Google Scholar , 7 Verstraete M Clark PA Wright IS Use of different tissue thromboplastins in the control of anticoagulant therapy. Circulation. 1957; 16: 213-226 Crossref PubMed Scopus (6) Google Scholar measured in the prothrombin time (PT) test; and the second is the reluctance of hematologists in North America to adopt the standardized international normalized ratio (INR) method of reporting which is now accepted internationally. In this update on oral anticoagulant therapy, we have made a number of changes. The first is to report our recommendations for therapeutic ranges of INR since recent reports indicate that the variations in responsiveness of commercial thromboplastins is so wide that the term typical North American thromboplastin is no longer valid. The second is to recommend an INR of 2.0 to 3.0 for all indications (including recurrent systemic embolism) except mechanical prosthetic heart valves for which an INR of 2.5 to 3.5 is recommended. The intensity of the therapeutic range has been lowered for mechanical prosthetic valves because of reports that a low intensity regimen is effective for this indication and because the risk of bleeding increases with increasing anticoagulant intensity. The third change is an expansion of this chapter to include mechanism of action of oral anticoagulants, their pharmacokinetics, practical dosing considerations, and the management of patients who require reversal or lowering of anticoagulant intensity.