Performance of the microINR Point-of-Care System Used by Self-Testing Patients: A Multicenter Clinical Trial.

Introduction Anticoagulation monitoring is a major practical and clinical challenge. We assessed the performance of the microINR system in patient self-testing (PST). Methods This study was performed at four US medical centers. After the training visit of warfarin anticoagulated patients ( n = 117) on microINR system, PST was performed at home and in two visits to the medical centers. At the medical centers, both PST and healthcare professionals (HCPs) performed duplicate tests with the microINR System. A venous blood sample for the laboratory testing was also extracted. Accuracy and precision were assessed. Results The comparison between microINR PST results and microINR HCP results revealed an equivalence with a slope of 1.00 (95% confidence interval [CI]: 1.00-1.00), and an intercept of 0.00 (95% CI: 0.00-0.00). When compared with the laboratory analyzer, microINR PST results also showed good correlation with a slope of 0.94 (95% CI: 0.86-1.04) and an intercept of 0.14 (95% CI: -0.09-0.34). Predicted bias values at international normalized ratio (INR) 2.0, 3.5, and 4.5 were 0% against HCP and ≤2.5% against the laboratory. Analytical agreement with both HCP and laboratory was 100% according to ISO17593 and 99.1 and 100% according to CLSI POCT14 with HCP and laboratory, respectively. Clinical agreement with HCP regarding 2.0-4.0 as INR therapeutic range was 98% (within range). The precision (coefficient of variation) of microINR system used by PST was comparable to HCP. Conclusion The microINR results when used by self-testing patients show satisfactory concordance to both HCP results and laboratory analyzer. The microINR system is adequate for self-testing use.

At-Home Versus In-Clinic INR Monitoring: A Cost-Utility Analysis from The Home INR Study (THINRS).

BACKGROUND: Effective management of patients using warfarin is resource-intensive, requiring frequent in-clinic testing of the international normalized ratio (INR). Patient self-testing (PST) using portable at-home INR monitoring devices has emerged as a convenient alternative. As revealed by The Home INR Study (THINRS), event rates for PST were not significantly different from those for in-clinic high-quality anticoagulation management (HQACM), and a cumulative gain in quality of life was observed for patients undergoing PST. OBJECTIVE: To perform a cost-utility analysis of weekly PST versus monthly HQACM and to examine the sensitivity of these results to testing frequency. PATIENTS/INTERVENTIONS: In this study, 2922 patients taking warfarin for atrial fibrillation or mechanical heart valve, and who demonstrated PST competence, were randomized to either weekly PST (n = 1465) or monthly in-clinic testing (n = 1457). In a sub-study, 234 additional patients were randomized to PST once every 4 weeks (n = 116) or PST twice weekly (n = 118). The endpoints were quality of life (measured by the Health Utilities Index), health care utilization, and costs over 2 years of follow-up. RESULTS: PST and HQACM participants were similar with regard to gender, age, and CHADS2 score. The total cost per patient over 2 years of follow-up was $32,484 for HQACM and $33,460 for weekly PST, representing a difference of $976. The incremental cost per quality-adjusted life year gained with PST once weekly was $5566 (95 % CI, -$11,490 to $25,142). The incremental cost-effectiveness ratio (ICER) was sensitive to testing frequency: weekly PST dominated PST twice weekly and once every 4 weeks. Compared to HQACM, weekly PST was associated with statistically significant and clinically meaningful improvements in quality of life. The ICER for weekly PST versus HQACM was well within accepted standards for cost-effectiveness, and was preferred over more or less frequent PST. These results were robust to sensitivity analyses of key assumptions. CONCLUSION: Weekly PST is a cost-effective alternative to monthly HQACM and a preferred testing frequency compared to twice weekly or monthly PST.

The impact of frequency of patient self-testing of prothrombin time on time in target range within VA Cooperative Study #481: The Home INR Study (THINRS), a randomized, controlled trial.

Anticoagulation (AC) is effective in reducing thromboembolic events for individuals with atrial fibrillation (AF) or mechanical heart valve (MHV), but maintaining patients in target range for international normalized ratio (INR) can be difficult. Evidence suggests increasing INR testing frequency can improve time in target range (TTR), but this can be impractical with in-clinic testing. The objective of this study was to test the hypothesis that more frequent patient-self testing (PST) via home monitoring increases TTR. This planned substudy was conducted as part of The Home INR Study, a randomized controlled trial of in-clinic INR testing every 4 weeks versus PST at three different intervals. The setting for this study was 6 VA centers across the United States. 1,029 candidates with AF or MHV were trained and tested for competency using ProTime INR meters; 787 patients were deemed competent and, after second consent, randomized across four arms: high quality AC management (HQACM) in a dedicated clinic, with venous INR testing once every 4 weeks; and telephone monitored PST once every 4 weeks; weekly; and twice weekly. The primary endpoint was TTR at 1-year follow-up. The secondary endpoints were: major bleed, stroke and death, and quality of life. Results showed that TTR increased as testing frequency increased (59.9 ± 16.7 %, 63.3 ± 14.3 %, and 66.8 ± 13.2 % [mean ± SD] for the groups that underwent PST every 4 weeks, weekly and twice weekly, respectively). The proportion of poorly managed patients (i.e., TTR <50 %) was significantly lower for groups that underwent PST versus HQACM, and the proportion decreased as testing frequency increased. Patients and their care providers were unblinded given the nature of PST and HQACM. In conclusion, more frequent PST improved TTR and reduced the proportion of poorly managed patients.

Improving transitions of care for patients with thromboembolic disease.

Patients with or at risk for thromboembolic disease have many transitional interactions within the healthcare system. Transitions of care--when patients move between or within sites of care, or transition from inpatient to outpatient status--create repeated and diverse opportunities for medication errors, rehospitalization, and other adverse events that may increase costs. Although effective antithrombotic therapies are available, these therapies are complex, underprescribed, and frequently suboptimally managed, a situation further exacerbated by poor patient adherence to therapy. Physician and patient education may help address knowledge gaps related to antithrombotic therapy to help ensure that patients receive appropriate therapy and adhere to the therapeutic regimen. Due to the complexities of antithrombotic therapy it is not surprising that when these patients experience transitions of care, the potential for errors and suboptimal outcomes becomes compounded. Efforts are under way to improve the process of transitional care, including the development of protocols for medication reconciliation, improved communication between clinicians at hand-off, the use of electronic medical records, and the introduction of a collaborative approach among different types of healthcare providers, including pharmacists, nurses, and care managers, so that transitional care is provided smoothly and safely.

Heart rate control in patients with chronic atrial fibrillation and heart failure.

The goal of this study was to determine whether aggressive heart rate (HR) control in patients with both chronic atrial fibrillation (AF) and heart failure (HF) is associated with improved outcomes. HR control is one of the mainstays in management of patients with AF. However, rate control can be challenging in patients with HF. This study was designed as an interventional clinical trial, using patients with chronic AF and left ventricular systolic dysfunction with left ventricular ejection fraction ≤40% (n=20) as their own controls. Intervention consisted of increasing doses of metoprolol succinate to achieve target resting HR <70 beats per minute. Clinical data were collected at baseline and after intervention, with paired t test used to evaluate statistically significant change. After 3 months of intervention, average resting HR decreased from 94±14 beats per minute to 85±12 beats per minute. Average metoprolol succinate dose at the end of the study was 121 mg. None of the outcomes improved significantly after the intervention, including exercise tolerance (meters walked on 6-minute walk test 326±83 vs 330±86), quality of life (Minnesota Living With Heart Failure Questionnaire score of 42.5±19 vs 38±21), and brain natriuretic peptide (242±306 pg/mL vs 279±395 pg/mL). Aggressive HR control was difficult in this group of patients with chronic AF and HF due to patient intolerance of increasing doses of ß-blockade, and not associated with improved outcomes. Further studies are needed to establish guidelines for target HR in patients with chronic AF who also have significant HF.

An evaluation of patient self-testing competency of prothrombin time for managing anticoagulation: pre-randomization results of VA Cooperative Study #481--The Home INR Study (THINRS).

Prior studies suggest patient self-testing (PST) of prothrombin time (PT) can improve the quality of anticoagulation (AC) and reduce complications (e.g., bleeding and thromboembolic events). "The Home INR Study" (THINRS) compared AC management with frequent PST using a home monitoring device to high-quality AC management (HQACM) with clinic-based monitoring on major health outcomes. A key clinical and policy question is whether and which patients can successfully use such devices. We report the results of Part 1 of THINRS in which patients and caregivers were evaluated for their ability to perform PST. Study-eligible patients (n = 3643) were trained to use the home monitoring device and evaluated after 2-4 weeks for PST competency. Information about demographics, medical history, warfarin use, medications, plus measures of numeracy, literacy, cognition, dexterity, and satisfaction with AC were collected. Approximately 80% (2931 of 3643) of patients trained on PST demonstrated competency; of these, 8% (238) required caregiver assistance. Testers who were not competent to perform PST had higher numbers of practice attempts, higher cuvette wastage, and were less able to perform a fingerstick or obtain blood for the cuvette in a timely fashion. Factors associated with failure to pass PST training included increased age, previous stroke history, poor cognition, and poor manual dexterity. A majority of patients were able to perform PST. Successful home monitoring of PT with a PST device required adequate levels of cognition and manual dexterity. Training a caregiver modestly increased the proportion of patients who can perform PST.

Improving antithrombotic management in patients with atrial fibrillation: current status and perspectives.

Despite overwhelming evidence of the benefits of risk-adjusted oral anticoagulation on stroke reduction in patients with atrial fibrillation (AF), there is still considerable undertreatment. A multidisciplinary expert group was formed to discuss issues surrounding anticoagulant treatment of patients with AF to try and achieve consensus on various aspects of the implementation of guidelines on oral anticoagulation therapy in AF. Panel members were cardiologists, hematologists, and laboratory and primary care physicians with specific expertise from Europe and the United States. One of the most important conclusions of the meeting was to enhance guideline adherence by better communication of the data showing that the benefits of stroke reduction outweigh the risk of bleeding associated with treatment with vitamin K antagonists. Management of oral anticoagulation therapy by dedicated centers, such as anticoagulation clinics, or by patient self-management may improve the quality of anticoagulation and facilitate the management of these patients and thereby further facilitate optimal antithrombotic management in patients with AF.

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.

The impact of patient self-testing of prothrombin time for managing anticoagulation: rationale and design of VA Cooperative Study #481--the Home INR Study (THINRS).

BACKGROUND: Anticoagulation (AC) with warfarin reduces the risk of thromboembolism (TE) in a variety of applications, yet despite compelling evidence of the value and importance of high quality AC, warfarin remains underused, and dosing is often suboptimal. Approaches to improve AC quality include (1) an AC service (ACS), which allows the physician to delegate day-to-day details of AC management to another provider dedicated to AC care, and (2) incorporating into the treatment plan patient self-testing (PST) under which, after completing a training program, patients perform their own blood testing (typically, using a finger-stick blood analyzer), have dosage adjustments guided by a standard protocol, and forward test results, dosing and other information to the provider. Studies have suggested that PST can improve the quality of AC and perhaps lower TE and bleed rates. The purpose of Department of Veterans Affairs (VA) Cooperative Studies Program (CSP) #481, "The Home INR Study" (THINRS) is to compare AC management with frequent PST using a home monitoring device to high quality AC management (HQACM) implemented by an ACS with conventional monitoring of prothrombin time by international normalized ratio (INR) on major health outcomes. PST in THINRS involves use of an INR monitoring device that is FDA approved for home use. STUDY DESIGN: Sites are VA Medical Centers where the ACS has an active roster of more than 400 patients. THINRS includes patients with atrial fibrillation (AF) and/or mechanical heart valve (MHV) expected to be anticoagulated indefinitely. THINRS has two parts. In Part 1, candidates for PST are evaluated for 2 to 4 weeks for their ability to use home monitoring devices. In Part 2, individuals capable of performing PST are randomized to (1) HQACM with testing every 4 weeks and as indicated for out of range values, medication/clinical changes, or (2) PST with testing every week and as indicated for out of range values, medication/clinical changes. The primary outcome measure is event rates, defined as the percent of patients who have a stroke, major bleed, or die. Secondary outcomes include total time in range (TTR), other events (myocardial infarction (MI), non-stroke TE, minor bleeds), competence and compliance with PST, satisfaction with AC, AC associated quality of life (QOL), and cost-effectiveness. To assess the effect of PST frequency on TTR and other outcomes, at selected sites patients randomized to perform PST are assigned one of three test frequencies (weekly, twice weekly, or once every four weeks).

Amiodarone versus sotalol for atrial fibrillation.

BACKGROUND: The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 665 patients who were receiving anticoagulants and had persistent atrial fibrillation to receive amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and monitored them for 1 to 4.5 years. The primary end point was the time to recurrence of atrial fibrillation beginning on day 28, determined by means of weekly transtelephonic monitoring. RESULTS: Spontaneous conversion occurred in 27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8 percent of the placebo group, and direct-current cardioversion failed in 27.7 percent, 26.5 percent, and 32.1 percent, respectively. The median times to a recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days in the sotalol group, and 6 days in the placebo group according to intention to treat and 809, 209, and 13 days, respectively, according to treatment received. Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and sotalol was superior to placebo (P<0.001). In patients with ischemic heart disease, the median time to a recurrence of atrial fibrillation was 569 days with amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and maintenance of sinus rhythm significantly improved the quality of life and exercise capacity. There were no significant differences in major adverse events among the three groups. CONCLUSIONS: Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

Increased P-wave dispersion predicts recurrent atrial fibrillation after cardioversion.

Atrial fibrillation (AF) will recur in a number of patients treated with cardioversion. Being able to identify reliable risk factors would be useful for making management decisions. P-wave dispersion (PWD) is an electrocardiographic measurement, which reflects a disparity in atrial conduction. P-wave dispersion has been shown to be increased in patients with paroxysmal AF. This pilot study aims to determine the role of PWD in predicting AF recurrence in patients who underwent elective cardioversion. Forty-five patients who were successfully cardioverted for persistent AF were included for study. Eighteen patients had a PWD greater than 80 ms; of these 13 had AF recurrence. Of the 25 patients with PWD less than 80 milliseconds, 12 had recurrent AF. P-wave dispersion values greater than 80 milliseconds were found more frequently in patients with AF recurrence (P = .05), supporting the use of this parameter in predicting return of AF. Larger studies are needed for further evaluation.

Platelet ADP receptor antagonists: ticlopidine and clopidogrel.

The central role of platelets in the pathophysiology of arterial vascular disease has focused attention on the development of effective platelet inhibitor modalities to mitigate the clinical consequences of atherothrombotic disease. Aspirin has been the gold standard of therapy and is effective in cerebral, coronary and peripheral arterial disease with a 25% reduction in myocardial infarction, stroke and vascular death. The platelet ADP receptor antagonists were developed to further improve the clinical results of therapy. Ticlopidine provides an additional 10% relative risk reduction over aspirin alone in stroke prevention and coronary stent placement. However, ticlopidine is accompanied by occasional life-threatening adverse hematological events. The action of clopidogrel is similar to that of ticlopidine, and it is comparably effective. However, the side-effect profile of clopidogrel is much more favorable.

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T]).

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

The North American experience with patient self-testing of the INR.

The increased utilization of anticoagulant therapy has led to a spectrum of advances in management, including the use of International Normalized Ratio (INR) reporting, the development of anticoagulation clinics, the development of portable point-of-care INR devices, and the development of innovative testing modalities such as patient self-testing (PST). PST of the INR provides improved access to testing and a practical method to achieve high-frequency testing, typically on a once-a-week schedule. Implementation of self-testing has been widely adopted in Germany but has been accepted much more slowly in North America. The lack of effective reimbursement has been the greatest barrier to more widespread use of PST, but this is confounded by the lack of large-scale clinical trials, INR issues, and the lack of physician awareness and advocacy. Recent decisions by insurance authorities to provide limited reimbursement are providing some optimism for more widespread utilization of PST of the INR in the near future.

Effect of Programmed Atrioventricular Delay on the Patterns of Mitral and Pulmonary Vein Flow Profiles and Their Durations in Patients with Dual-Chamber Pacemakers.

Cardiac pacemakers are increasingly used in patients with dilated and hypertrophic cardiomyopathy. In these patients, unusually short atrioventricular (AV) delays are used. Changing the AV delay has been shown to affect the mitral E/A velocity ratio, but its effect on the duration of left ventricular (LV) isovolumic relaxation time, LV filling time, or pulmonary vein flow pattern has not been investigated. Twelve patients with dual-chamber pacemakers were studied. The pacemaker was set at a rate of 70 beats/min, and the AV delay was programmed from 25 to 250 msec in 25-msec increments. At each stage, mitral and pulmonary vein flow velocities were recorded using pulsed-wave Doppler technique. Increasing AV delay resulted in a shortened LV diastolic filling period, a change in LV isovolumic relaxation time, a reduction in the E/A velocity ratio, and an increase in A - AR wave duration. These findings have implications not only in the optimization of LV filling but also in the interpretation of mitral and pulmonary vein flow profiles in the evaluation of LV diastolic function and filling pressures.