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- MATERIALS AND METHODS
OBJECTIVES: To determine the effect of patient characteristics and of specific guidelines that were developed for managing warfarin therapy in older adults and included in an in-house computer program on anticoagulation quality.
DESIGN: Thirteen-month observational study.
SETTING: Acute care, extended care, and rehabilitation geriatric wards of a teaching hospital in Paris, France.
PARTICIPANTS: Hospitalized patients (N=307, mean age 86.1 ± 6.1) treated with warfarin with a therapeutic international normalized ratio range of 2.0 to 3.0.
INTERVENTION: Patients were assigned according to care unit to the computer-generated dosing group (CGD) or the standard management group (SM; usual physician-based care).
MEASUREMENTS: Relationships between anticoagulation quality criteria and covariates (age, sex, warfarin indication, treatment phase, follow-up duration, model of care).
RESULTS: According to multivariate analysis, only model of care and follow-up duration independently influenced anticoagulation control; the proportion of time within therapeutic INR range 2.0 to 3.0 was significantly greater in the CGD group than in the SM group (59% vs 48%, P=.004). When a wider INR range was analyzed (1.8–3.2), the proportion of time within range was 73% versus 64% (P=.006). Use of the computer was associated with fewer days with INRs greater than 3, a smaller percentage of INRs of 4 or greater, a longer time to the first INR of 4.0 or greater, and a smaller mean number of INRs per month than SM (all P<.01).
CONCLUSION: Initiation regimen and long-term rules that have specifically been developed and included in a computerized dosage program improve quality of anticoagulation in elderly inpatients, allowing them to benefit from a quality of care as high as that of younger ambulatory patients.
The number of elderly patients who require warfarin therapy is rising steadily, because the aging of the population is causing increases in the prevalences of atrial fibrillation and venous thromboembolism. Warfarin has a narrow therapeutic index, so achieving effective yet safe anticoagulation is challenging,1 especially in frail elderly patients, who are at high risk of bleeding.2 To minimize the risks associated with anticoagulant therapy, anticoagulation clinics have been developed and shown to improve outcomes more than standard care.2 Computer programs are generally used in anticoagulation clinics to determine warfarin dosages,2–5 but no computer programs specifically designed for elderly patients are available, although the use of specific algorithms for treatment initiation and closer monitoring are recommended in elderly patients to maximize time spent within the therapeutic range.2,6,7 In a previous study, a warfarin induction algorithm specifically designed for elderly inpatients and based on the international normalized ratio (INR) measured after three daily intakes of 4 mg was validated.8 Rules were then developed for adjusting warfarin dosages after Day 3. These induction and adjustment guidelines were included in a computer program for assisting in warfarin dosage selection in elderly inpatients. Various considerations were taken into account to design the elderly-specific computer-generated dosing software. Elderly patients require lower dosages than younger patients, although the mechanism for this greater sensitivity to warfarin with aging is not well understood; they are more prone to instability, because they often have comorbidities and use drugs that interact with warfarin, and their response to warfarin dosage adjustments is slower.2,6,7
The main aim of this observational study conducted in elderly inpatients treated with warfarin with a target INR range of 2.0 to 3.0 was to assess the effect of the computer program on anticoagulation control, especially on the time spent in the therapeutic range. The effect of patient characteristics on anticoagulation quality was also evaluated.
- Top of page
- MATERIALS AND METHODS
This study showed that software specifically designed to assist in warfarin dose determination in elderly inpatients resulted in better anticoagulation quality in hospitalized elderly patients than dose determination by the physicians. The 10 percentage points greater time spent within the therapeutic range is of similar magnitude to improvements reported earlier in studies comparing usual care with different models of intervention.5,13,14 A greater improvement would probably have been found had the hospital physicians not received specific training in warfarin dose management in elderly patients.
Despite evidence that warfarin is highly effective in preventing thromboembolism, it remains underused in elderly patients. Concern about inducing bleeding events and anticipated difficulties with anticoagulation control have been suggested as indications for not prescribing warfarin to elderly patients.6 Few data are available to guide clinicians in determining warfarin dosages for older adults. In most warfarin regimens, the initial dose of 10 mg often causes overanticoagulation during treatment induction in older patients, and the subsequent doses are determined using a nomogram based on the results of the daily INR value.6,8 Moreover, no protocols concerning the dose adjustments during the maintenance phase in older adults are available. The rules presented here and that were used in the computer program to manage the care of patients receiving warfarin treatment consisted of the algorithm that predicts the maintenance dosage from an INR value measured after the third daily intake of a 4-mg dose.8 This algorithm was extended beyond Day 3 using rules to manage long-term anticoagulation therapy in older adults. With the software, elderly inpatients spent 59% of the time within the therapeutic INR range 2.5 ± 0.5 and 73% within the INR range of 2.5 ± 0.7. This second, wider range is the range for which no dosage adjustments are systematically performed.
Previous studies comparing standard management with other approaches show considerable heterogeneity, particularly regarding design (retrospective or prospective), setting (hospital or community), and patient characteristics.2 In a systematic review of 67 studies representing more than 50,000 patients from anticoagulation clinics (68%), clinical trials (7%), or community practices (24%), the overall percentage of time spent in the therapeutic INR range was 63.5% (60.6% in patients treated with warfarin).13 Practice setting had the greatest effect on anticoagulation control, with time within the therapeutic range varying from 56.7% in community practices to 66.4% in randomized trials.13 Of the 67 studies, only two included all INR measurements, as opposed to only INRs performed as part of the anticoagulation management service.13 INR values obtained during acute illnesses are probably less often within the therapeutic range than those obtained as part of oral anticoagulant monitoring. In the current study, all INR values were included. In a retrospective population-based study of elderly patients (mean age 77 ± 7), the percentage of time spent within the therapeutic range (2.0–3.0) was 59.2% overall and was 15% smaller in hospitalized patients than in outpatients.15 In a study conducted in five countries (Canada, France, Italy, Spain, and the United States) to assess anticoagulation control in ambulatory patients with chronic nonvalvular atrial fibrillation requiring vitamin K antagonist therapy for stroke prophylaxis, the percentage of time with INR values between 2.0 and 3.0 in the 1,511 included patients ranged from 58% to 69.5% (59.3% in France).16 In an observational study of interventions to improve anticoagulation management by general practitioners in Belgium, including a CGD program, the percentage of time spent within 0.75 INR units from the chosen target of 2.5 or 3.5 in the study population with a mean age of 70 ranged across interventions from 73% to 80%.17 Finally, in a recent study in a population similar to that of the current study (110 hospitalized patients with a mean age of 85) managed without a dose-adjustment protocol, the time within the therapeutic range (2.0–3.0) was only 31%.18 The high rate of INRs within the therapeutic range obtained using the software is particularly remarkable, because the patients in the current study were hospitalized and older than those in previous studies and therefore more prone to anticoagulation instability due to polypharmacy and comorbid conditions. The software also significantly decreased overanticoagulation (percentage of days spent with INR values ≥4.0 and time to the first INR ≥4.0). Concern about overanticoagulation may make physicians reluctant to use anticoagulants in elderly patients. The results of the current study suggest that specific management may overcome this obstacle to appropriate anticoagulant therapy. Finally, using the software decreased the number of required INR determinations. Because the frequency of INR testing differed between the two management groups, it was determined that the better anticoagulation control in the computer group than in the standard management group was not related to the frequency of INR testing; there was a statistical relationship between the time spent within the two INR ranges and the frequency of INR testing, but after adjustment for INR frequency, the model of care and the time spent within the two INR ranges were independently associated.
The sample size was too small for an assessment of the effects of CGD on patient outcomes, but there is widespread agreement that anticoagulation control influences anticoagulation-related outcomes.1,2,14,19,20 Thus, improving anticoagulation control and minimizing INR fluctuations using a computer-assisted warfarin management system specifically devoted to elderly patients would probably result in better clinical outcomes in this population.
One limitation of this study is the absence of random allocation to the treatment groups. It is unlikely that this accounted for the difference in the quality of anticoagulation between the two management systems, because the two groups were similar in age, sex, indication for anticoagulation, and duration of follow-up. Because patients participating in population-based intervention studies cannot easily be randomized or blinded to treatment condition, and because investigators cannot be blinded to treatment condition, even randomized studies can be biased.
In conclusion, the present study, in which rules of warfarin management are proposed, provides evidence that initiation regimen and long-term rules specifically devoted to elderly patients and included in a computerized dosage program, allow hospitalized elderly patients to benefit from a quality of care as high as that of younger ambulatory patients.