Standardised initial warfarin treatment: evaluation of initial treatment response and maintenance dose prediction by randomised trial, and risk factors for an excessive warfarin response

Abstract

We report a comparison of warfarin treatment outcomes in 172 inpatients in two general hospitals randomly assigned to commence warfarin therapy by one of two methods; the first where warfarin dosage was determined using a flexible dose induction protocol, and the other where dosage was prescribed empirically by resident medical staff. The mean INR for each treatment day, the mean time to reach a therapeutic level of INR, the mean maintenance dose and the mean time to reach maintenance dose were not significantly different between the protocol and empirical treatment groups. Although the mean observations of warfarin effect were similar between the two groups, there were more patients with excessive warfarin effect (INR greater than 4.0) during empirical treatment. In addition, age and identified complicating factors such as interfering drugs, heart failure or alcohol abuse were significant predictors of excessive warfarin effect, regardless of treatment group. The protocol dose administered on day 4 of treatment, which has been used as a determinant of maintenance dose, predicted maintenance dose to within 1 mg in 57/83 patients (69%, 95% confidence interval: 59-79%). We conclude that as a method for safely and effectively initiating warfarin therapy, this protocol at least matches the empirical prescribing skills of medical staff in a teaching hospital.

Evidence-Based Management of Anticoagulant Therapy

“…46,[78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97] These dosing adjuncts have been studied at the initiation of therapy (no prior VKA doses) and during the maintenance phase of therapy and were compared with dose deci sions made without the use of decision support (manual dosing). Both nomogram/computer-assisted and manual dosing were performed by experienced anticoagulation providers in some studies 78,86,87,90,91 and by providers without specialized training (eg, trainee physicians, house staff, regular physician, nurses) in others.…”

“…Both nomogram/computer-assisted and manual dosing were performed by experienced anticoagulation providers in some studies 78,86,87,90,91 and by providers without specialized training (eg, trainee physicians, house staff, regular physician, nurses) in others. 46,[79][80][81][82][83][84][85]88,89,[92][93][94][95] Decision support-guided dosing (paper nomograms or computer programs) performed no better than manual dosing during initiation of VKA therapy in pooled analyses of available RCTs ( Table 7 , Table S7). Pooled analyses of RCTs evaluating decision supportguided dosing during maintenance therapy (all were computer-assisted dosing programs) revealed a mean TTR improvement of 4.5% (95% CI, 2.4%-6.7%) compared with no decision support.…”

“…13,000 events, 78-80,82,86-88,90-92 79 Doecke et al, 82 Kovacs et al, 85 Landefeld and Anderson, 46 Vadher et al, 92 van den Bemt et al, 94 and White et al 95 e Asnis et al, 79 Doecke et al, 82 Kovacs et al, 85 Landefeld and Anderson, 46 and Vadher et al 92 f Claes et al, 81 Fitzmaurice et al, 83 Fitzmaurice et al, 84 Mitra et al, 88 Poller et al, 91 Vadher et al, 92 and Vadher et al 93 g Claes et al, 81 Fitzmaurice et al, 83 Fitzmaurice et al, 84 Poller et al, 91 and Vadher et al 93 h Claes et al, 81 Fitzmaurice et al, 83 Fitzmaurice et al, 84 Poller et al, 89 and Poller et al 91 measured hemorrhage as the clinical outcome. In general, the quality of evidence from these studies was low.…”

Prospective Assessment of a Nomogram for the Initiation of Oral Anticoagulation Therapy for Outpatient Treatment of Venous Thromboembolism

“…Nomograms for the initiation of warfarin have been described in the past and have been shown to be superior to standard care [6][7][8]. Recently, a warfarin nomogram published based on initiation of a maintenance dose (5 mg) has been suggested to be as efficacious as traditional higher doses of initiation [9,10].…”

Quality measures and benchmarking for warfarin therapy

“…Various methods have been used to improve the quality of warfarin dose adjustment including the use of manual algorithms and computerized dosing decision support software. In comparison with empiric dosing manual nomograms appear to perform at least as well during the initiation phase and seem to provide better TTR during maintenance therapy [23][24][25][26][27]. In contrast, computerized dosing programs have not demonstrated improved definitive outcomes, but there is also no evidence that computer-assisted warfarin dosing puts patients at any added risk compared with dosage by experienced medical staff [28].…”