Comparing Self-Management of Oral Anticoagulant Therapy with Clinic Management

Context Although many outpatients require oral anticoagulation, the optimal management of outpatient anticoagulation remains uncertain. Studies have demonstrated the feasibility of patient self-management using portable coagulometers, but the studies that compared patient outcomes with self-management and those with conventional management in an anticoagulation clinic did not find a better outcome with self-management. Contribution In this randomized, controlled trial of 737 patients, patients assigned to self-management of anticoagulation achieved a similar level of control and had fewer adverse events than patients assigned to conventional management. Implications Health care providers should begin to implement patient self-management of oral anticoagulation with portable coagulometers in mainstream practice. The Editors Indications for oral anticoagulant treatment to prevent thromboembolic disease have increased in recent years (1). Prothrombin times must be monitored frequently in patients taking oral anticoagulants to determine the safest dose and to minimize the risk for complications. The clinical management of oral anticoagulant treatment improved greatly after the international normalized ratio (INR) was introduced as a measurement of anticoagulation intensity (1). The establishment of accurate therapeutic INR ranges was also beneficial. Target ranges include the safest INR values that carry the lowest risk for hemorrhagic or thromboembolic complications (2). Despite these improvements, however, serious complications are still associated with oral anticoagulant treatment (3, 4), and management by specialized staff at anticoagulation clinics seems to be safer than other clinical strategies in terms of numbers of complications (5-7). Currently, portable coagulometers are available for determining INR easily and reliably (8). This technology provides interesting clinical models for the control of oral anticoagulant treatment, the most promising of which are patient self-testing and patient self-management. For patient self-testing, patients measure INRs themselves and ask their referring physicians for the proper anticoagulant dose. Patient self-management assumes that patients will adjust their own doses and is the most autonomous strategy. Several published studies have compared these strategies with usual care (that is, monitoring of oral anticoagulant treatment by practitioners) (9-13) or with specialized anticoagulation clinics (14-18). Although these studies showed that both patient self-testing and patient self-management are feasible, their samples were relatively small (9, 11, 13, 14-18) or included selected patients with mechanical valve prostheses (10) or patients older than 65 years of age (12). In general, previous studies indicate that patient self-management may be superior to management by general practitioners or anticoagulation clinics in quality of INR control (10-18). In addition, Krtke and Krfer (10), Beyth and associates (12), and Sawicki (13) reported a decrease in major complications among self-managed patients compared with patients managed by general practitioners. To date, no published data have suggested a better clinical outcome (decrease in associated complications) with patient self-management than with specialized management at an anticoagulation clinic (5, 19). We performed a randomized, controlled trial to directly compare self-management of oral anticoagulant treatment, as evaluated in terms of efficacy and safety in unselected patients, with management in an anticoagulation clinic. Methods Study Design The Alternative Control of Oral Anticoagulant Treatment (ACOA) trial is a single-center, centrally randomized, controlled study that was performed at Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, from January 2001 to July 2002. The hematologists who manage our anticoagulation clinic use a homogeneous dosing protocol and standard protocols to manage situations that increase clinical risk. The clinical staff includes trained nurses. Computers control the clinical data and INR records, ensuring excellent follow-up. Patients and their relatives receive basic education at the beginning of oral anticoagulant treatment, including information on the main characteristics of oral anticoagulants, potential risks, rationale for periodic monitoring, and drug interactions. Samsa and Matchar (20) recommended that these characteristics be used to provide an appropriate control group in a trial on patient self-management. The institutional review board of our hospital approved the study. Recruitment Phase The recruitment phase began with computerized random selection of 1500 patients from the more than 5000 who were receiving oral anticoagulant treatment controlled in our hospital. We included any ambulatory patient 18 years of age or older who had been receiving long-term anticoagulant therapy for at least 3 months before entering the study. We excluded patients who were younger than 18 years of age, who had a severe physical or mental illness without a responsible caregiver, or who were of foreign origin and were unable to understand Spanish. Once the patient (or his or her caregiver) agreed to participate, written informed consent was obtained. Next, centralized telephone randomization assigned the patient to the experimental group (patient self-management) or to the control group (conventional management). The allocation sequence was generated at the hospital's epidemiology department, and the sequence of randomization was concealed until the patient was assigned to a group. To facilitate comparability between study groups, this randomization was stratified according to sex, age (70 years of age or <70 years of age), and indication for oral anticoagulant treatment (4 groups). Members of our anticoagulation clinic enrolled participants and assigned them to groups. Baseline data included demographic details, clinical information on associated risk factors, other medications, previous length of anticoagulant therapy, bleeding or thromboembolic complications during oral anticoagulant treatment, and target INR range. Follow-up for patients assigned to the conventional management group was done immediately. Patients in the self-management group received a training course first, and follow-up was not performed until the nurse teaching the course judged that the patients had acquired a minimum of expertise in self-management. Training Course An educational program was designed to optimize the number of patients able to understand and safely perform self-management (Appendix). It was similar to the German program developed by Sawicki (13) but was demographically adapted to the characteristics of the Spanish population, considering differences in daily schedules, diet, educational level, and other idiosyncratic factors. The program consisted of 2 sessions of 2 hours each on consecutive days. A specially trained nurse was responsible for teaching the patients in small, organized groups. The lessons included basic theoretical and practical concepts involving the use of a coagulometer, interpretation of INR, and adjustment of dose. The concepts of target range and dose modification were emphasized when necessary. A simple card system was designed to help the patient select the correct dose. For each target range, a specific card was provided. Patients were taught to use the portable coagulometer CoaguChek S (Roche Diagnostics, Mannheim, Germany) with the appropriate reagent strips. Follow-up Phase Normally, the patients in the conventional management group visited our hospital every 4 weeks to check their INRs. When the INR result was out of target range, our dosing protocol indicated that we should advance the next appointment for INR testing to 1 or 2 weeks. International normalized ratio was determined by means of a standard KC 10 coagulometer (Amelung, Lemgo, Germany). As a thromboplastin, we used Thromborel S (Behring, Marburg, Germany). A hematologist experienced in oral anticoagulation management adjusted the dose and made the appointment for the next INR test. Patients in the self-management group performed the INR tests at home once per week using the CoaguChek S kit. They determined the appropriate dose of oral anticoagulant and the time of the next INR test. All of the INR results in both groups were entered into a computer (in the central system of our anticoagulation clinic or in the portable coagulometers) to facilitate data management. Patients in both groups were interviewed monthly by telephone to record any complications or changes in their health status. For the conventional management group, these interviews were done approximately midway between hospital visits. The questions addressed minor or major bleeding, thromboembolic events, episodic diseases, changes in long-term medications, and hospital stays. Associated complications were diagnosed and evaluated by a third physician who was not involved in the trial and was unaware of patients' study group. Standard criteria were used to diagnose any thromboembolic complications. Transient ischemic attack was diagnosed clinically by a neurologist, and superficial thrombophlebitis was diagnosed clinically by an angiologist. To diagnose stroke, arterial embolism, venous thromboembolism, pulmonary embolism, or valve thrombosis, we used widely accepted methods (computed tomography or magnetic nuclear resonance imaging, angiography, surgical diagnosis, Doppler ultrasonography, phlebography, lung angiography or ventilation-perfusion lung scanning, cardiac ultrasonography, or fluoroscopy). All thromboembolic complications were considered major events. Life-threatening bleeding or bleeding requiring transfusion or hospital admission was considered a major event. Any other bleeding was considered a minor event. Statistical Analysis Study outcomes were evaluated on an intention-to-treat basis and also on an on-treatment basis. Th