Archive for November, 2014

Question Definition and Eligibility Criteria for Managing Oral Anticoagulant Therapy

A systematic review of the literature was performed based on predefined criteria for the population at risk, the intervention or exposure evaluated, the outcomes assessed, and the methodology of the trials evaluated (Table 5). Based on this information and, when necessary, a consensus of opinion by the authors, recommendations and/or suggestions are proposed and graded according to the conventions defined in this supplement.

Practical dose management

Initiation and maintenance dosing

Following the administration of warfarin, an initial effect on the PT usually occurs within the first 2 or 3 days, depending on the dose administered, and an antithrombotic effect occurs within the next several days. Heparin should be administered concurrently when a rapid anticoagulant effect is required, and its administration should be overlapped with warfarin until the INR has been in the therapeutic range for at least 2 days. A loading dose (ie, > 20 mg) of warfarin is not recommended. A number of randomized studies have supported the use of a lower initiation dose. Harrison et al and Crowther et al found that in hospitalized patients, commencing with an average maintenance dose of 5 mg warfarin usually results in an INR of > 2.0 in 4 or 5 days with less excessive anticoagulation compared to that with an initial 10-mg dose.

Kovacs et al, however, found that in outpatients who had been treated for venous thromboembolism, an initial 10-mg dose for the first 2 days of therapy compared to a 5-mg dose resulted in a more rapid achievement of a therapeutic INR (1.4 days earlier) without a difference in rates of excessive anticoagulation. Thus, there is room for flexibility in selecting a starting dose of warfarin. Some clinicians prefer to use a larger starting dose (eg, 7.5 to 10 mg), while a starting dose of < 5 mg might be appropriate in the elderly, in patients with impaired nutrition liver disease, or congestive heart failure, and in patients who are at high risk of bleeding. When the INR has been in the therapeutic range on two measurements approximately 24 h apart, heparin therapy is discontinued.

If treatment is not urgent (eg, chronic stable atrial fibrillation), warfarin administration, without concurrent heparin administration, can be commenced out-of-hospital with an anticipated maintenance dose of 4 to 5 mg per day.

Table 1—Question Definition and Eligibility Criteria for Managing Oral Anticoagulant Therapy

Section Population Intervention or Exposure Outcomes Methodology ExclusionCriteria
2.1 Patients starting oral anticoagulant therapy Initial dosing of VKA Recurrentthromboembolism; major and minor hemorrhages; time to achieve therapeutic INR RCT None
2.1.2 Elderly on oral anticoagulants VKA therapy Major hemorrhage or thrombosis; anticoagulant response; maintenance dose RCT and observational None
2.1.5 Patients receiving oral anticoagulants undergoing invasive procedures Use of alternative therapies (no therapy, UFH, or LMWH) Major and minor hemorrhage and thromboembolism RCT and observational None
2.2.2 Patients receiving oral anticoagulants VKA therapy TTR, quality of anticoagulation RCT and observational None
2.2.3 Patients receiving oral anticoagulants and in therapeutic range VKA therapy Major hemorrhage or thrombosis RCT and observational None
2.2.5 Patients receiving oral anticoagulants and bleeding Management of bleeding Hemorrhage or thrombosis RCT and observational None
2.3.1 Patients receiving oral anticoagulants ACC vs routine or UC Hemorrhage or thrombosis RCT and observational None
2.3.2 Patients receiving oral anticoagulants POC monitoring, PST, PSM, orcomputerized dose management TTR, major hemorrhage or thrombosis RCT and observational None
2.3.3 Patients receiving oral anticoagulants Different models of care: ACC vs UC vs PST vs PSM Cost-effectiveness RCT, cohort, crossover, and observational None