Warfarin utilisation and anticoagulation control in patients with atrial fibrillation and chronic kidney disease.

OBJECTIVE: To evaluate warfarin prescription, quality of international normalised ratio (INR) monitoring and of INR control in patients with atrial fibrillation (AF) and chronic kidney disease (CKD). METHODS: We performed a retrospective cohort study of patients with newly diagnosed AF in the Veterans Administration (VA) healthcare system. We evaluated anticoagulation prescription, INR monitoring intensity and time in and outside INR therapeutic range (TTR) stratified by CKD. RESULTS: Of 123 188 patients with newly diagnosed AF, use of warfarin decreased with increasing severity of CKD (57.2%-46.4%), although it was higher among patients on dialysis (62.3%). Although INR monitoring intensity was similar across CKD strata, the proportion with TTR≥60% decreased with CKD severity, with only 21% of patients on dialysis achieving TTR≥60%. After multivariate adjustment, the magnitude of TTR reduction increased with CKD severity. Patients on dialysis had the highest time markedly out of range with INR <1.5 or >3.5 (30%); 12% of INR time was >3.5, and low TTR persisted for up to 3 years. CONCLUSIONS: There is a wide variation in anticoagulation prescription based on CKD severity. Patients with moderate-to-severe CKD, including dialysis, have substantially reduced TTR, despite comparable INR monitoring intensity. These findings have implications for more intensive warfarin management strategies in CKD or alternative therapies such as direct oral anticoagulants.

Feasibility of extended ambulatory electrocardiogram monitoring to identify silent atrial fibrillation in high-risk patients: the Screening Study for Undiagnosed Atrial Fibrillation (STUDY-AF).

BACKGROUND: Identification of silent atrial fibrillation (AF) could prevent stroke and other sequelae. HYPOTHESIS: Screening for AF using continuous ambulatory electrocardiographic (ECG) monitoring can detect silent AF in asymptomatic in patients with known risk factors. METHODS: We performed a single-center prospective screening study using a wearable patch-based device that provides up to 2 weeks of continuous ambulatory ECG monitoring (iRhythm Technologies, Inc.). Inclusion criteria were age ≥55 years and ≥2 of the following risk factors: coronary disease, heart failure, hypertension, diabetes, sleep apnea. We excluded patients with prior AF, stroke, transient ischemic attack, implantable pacemaker or defibrillator, or with palpitations or syncope in the prior year. RESULTS: Out of 75 subjects (all male, age 69 ± 8.0 years; ejection fraction 57% ± 8.7%), AF was detected in 4 subjects (5.3%; AF burden 28% ± 48%). Atrial tachycardia (AT) was present in 67% (≥4 beats), 44% (≥8 beats), and 6.7% (≥60 seconds) of subjects. The combined diagnostic yield of sustained AT/AF was 11%. In subjects without sustained AT/AF, 11 (16%) had ≥30 supraventricular ectopic complexes per hour. CONCLUSIONS: Outpatient extended ECG screening for asymptomatic AF is feasible, with AF identified in 1 in 20 subjects and sustained AT/AF identified in 1 in 9 subjects, respectively. We also found a high prevalence of asymptomatic AT and frequent supraventricular ectopic complexes, which may be relevant to development of AF or stroke. If confirmed in a larger study, primary screening for AF could have a significant impact on public health.

Association between success rate and citation count of studies of radiofrequency catheter ablation for atrial fibrillation: possible evidence of citation bias.

BACKGROUND: The preferential citation of studies with the highest success rates could exaggerate perceived effectiveness, particularly for treatments with widely varying published success rates such as radiofrequency catheter ablation for atrial fibrillation. METHODS AND RESULTS: We systematically identified observational studies and clinical trials of radiofrequency catheter ablation of atrial fibrillation between 1990 and 2012. Generalized Poisson regression was used to estimate association between study success rate and total citation count, adjusting for sample size, journal impact factor, time since publication, study design, and whether first or last author was a consensus-defined pre-eminent expert. We identified 174 articles meeting our inclusion criteria (36 289 subjects). After adjustment only for time since publication, a 10-point increase above the mean in pooled reported success rates was associated with a 17.8% increase in citation count at 5 years postpublication (95% confidence interval, 7.1-28.4%; P<0.001). After additional adjustment for impact factor, sample size, randomized trial design, and pre-eminent expert authorship, the association remained significant (18.6% increase in citation count; 95% confidence interval, 7.6-29.6%; P<0.0001). In this full model, time since publication, impact factor, and pre-eminent expert authorship were significant covariates, whereas randomized control trial design and study sample size were not. CONCLUSIONS: Among studies of radiofrequency catheter ablation of atrial fibrillation, high success rate was independently associated with citation count, which may indicate citation bias. To readers of the literature, radiofrequency catheter ablation of atrial fibrillation could be perceived to be more effective than the data supports. These findings may have implications for a wide variety of novel cardiovascular therapies.

Increased mortality associated with digoxin in contemporary patients with atrial fibrillation: findings from the TREAT-AF study.

BACKGROUND: Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF). OBJECTIVES: The goal of this study was to evaluate the association of digoxin with mortality in AF. METHODS: Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis. RESULTS: Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin. CONCLUSIONS: Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF.

Diagnostic utility of a novel leadless arrhythmia monitoring device.

Although extending the duration of ambulatory electrocardiographic monitoring beyond 24 to 48 hours can improve the detection of arrhythmias, lead-based (Holter) monitors might be limited by patient compliance and other factors. We, therefore, evaluated compliance, analyzable signal time, interval to arrhythmia detection, and diagnostic yield of the Zio Patch, a novel leadless, electrocardiographic monitoring device in 26,751 consecutive patients. The mean wear time was 7.6 ± 3.6 days, and the median analyzable time was 99% of the total wear time. Among the patients with detected arrhythmias (60.3% of all patients), 29.9% had their first arrhythmia and 51.1% had their first symptom-triggered arrhythmia occur after the initial 48-hour period. Compared with the first 48 hours of monitoring, the overall diagnostic yield was greater when data from the entire Zio Patch wear duration were included for any arrhythmia (62.2% vs 43.9%, p <0.0001) and for any symptomatic arrhythmia (9.7% vs 4.4%, p <0.0001). For paroxysmal atrial fibrillation (AF), the mean interval to the first detection of AF was inversely proportional to the total AF burden, with an increasing proportion occurring after 48 hours (11.2%, 10.5%, 20.8%, and 38.0% for an AF burden of 51% to 75%, 26% to 50%, 1% to 25%, and <1%, respectively). In conclusion, extended monitoring with the Zio Patch for ≤14 days is feasible, with high patient compliance, a high analyzable signal time, and an incremental diagnostic yield beyond 48 hours for all arrhythmia types. These findings could have significant implications for device selection, monitoring duration, and care pathways for arrhythmia evaluation and AF surveillance.

Differences and trends in stroke prevention anticoagulation in primary care vs cardiology specialty management of new atrial fibrillation: The Retrospective Evaluation and Assessment of Therapies in AF (TREAT-AF) study.

BACKGROUND: Atrial fibrillation and flutter (AF, collectively) cause stroke. We evaluated whether treating specialty influences warfarin prescription in patients with newly diagnosed AF. METHODS: In the TREAT-AF study, we used Veterans Health Administration health record and claims data to identify patients with newly diagnosed AF between October 2004 and November 2008 and at least 1 internal medicine/primary care or cardiology outpatient encounter within 90 days after diagnosis. The primary outcome was prescription of warfarin. RESULTS: In 141,642 patients meeting the inclusion criteria, the mean age was 72.3 ± 10.2 years, 1.48% were women, and 25.8% had cardiology outpatient care. Cardiology-treated patients had more comorbidities and higher mean CHADS2 scores (1.8 vs 1.6, P < .0001). Warfarin use was higher in cardiology-treated vs primary care only-treated patients (68.6% vs 48.9%, P < .0001). After covariate and site-level adjustment, cardiology care was significantly associated with warfarin use (odds ratio [OR] 2.05, 95% CI 1.99-2.11). These findings were consistent across a series of adjusted models (OR 2.05-2.20), propensity matching (OR 1.98), and subgroup analyses (OR 1.58-2.11). Warfarin use in primary-care-only patients declined from 2004 to 2008 (51.6%-44.0%, P < .0001), whereas the adjusted odds of warfarin receipt with cardiology care (vs primary care) increased from 2004 to 2008 (1.88-2.24, P < .0001). CONCLUSION: In patients with newly diagnosed AF, we found large differences in anticoagulation use by treating specialty. A divergent 5-year trend of risk-adjusted warfarin use was observed. Treating specialty influences stroke prevention care and may impact clinical outcomes.

Ability of microvolt T-wave alternans to modify risk assessment of ventricular tachyarrhythmic events: a meta-analysis.

BACKGROUND: Prior studies have indicated that the magnitude of risk association of microvolt T-wave alternans (MTWA) testing appears to vary with the population studied. We performed a meta-analysis to determine the ability of MTWA to modify risk assessment of ventricular tachyarrhythmic events (VTEs) and sudden cardiac death (SCD) across a series of patient risk profiles using likelihood ratio (LR) testing, a measure of test performance independent of disease prevalence. METHODS: We identified original research articles published from January 1990 to January 2011 that investigate spectrally derived MTWA. Ventricular tachyarrhythmic event was defined as the total and arrhythmic mortality and nonfatal sustained or implantable cardioverter-defibrillator-treated ventricular tachyarrhythmias. Summary estimates were created for positive and nonnegative MTWA results using a random-effects model and were expressed as positive (LR+) and negative (LR-) LRs. RESULTS: Of 1,534 articles, 20 prospective cohort studies met our inclusion criteria, consisting of 5,945 subjects predominantly with prior myocardial infarction or left ventricular dysfunction. Although there was a modest association between positive MTWA and VTE (relative risk 2.45, 1.58-3.79) and nonnegative MTWA and VTE (3.68, 2.23-6.07), test performance was poor (positive MTWA: LR+ 1.78, LR- 0.43; nonnegative MTWA: LR+ 1.38, LR- 0.56). Subgroup analyses of subjects classified as prior VTE, post-myocardial infarction, SCD-HeFT type, and MADIT-II type had a similar poor test performance. A negative MTWA result would decrease the annualized risk of VTE from 8.85% to 6.37% in MADIT-II-type patients and from 5.91% to 2.60% in SCD-HeFT-type patients. CONCLUSIONS: Despite a modest association, results of spectrally derived MTWA testing do not sufficiently modify the risk of VTE to change clinical decisions.

Cost-effectiveness of pharmacologic and invasive therapies for stroke prophylaxis in atrial fibrillation.

Atrial fibrillation is an abnormal heart rhythm characterized by rapid, disorganized activation (fibrillation) of the left and right atria of the heart, and is responsible for 15% of 700,000 strokes in the United States each year. There are multiple pharmacologic and nonpharmacologic therapies used for stroke prevention in atrial fibrillation, including vitamin K antagonists such as warfarin, antiplatelet agents such as aspirin and clopidogrel, and newer agents such as dabigatran, rivaroxaban and apixaban. Nonpharmacologic therapies involve excluding the left atrial appendage from the systemic circulation by surgical ligation or excision, percutaneous ligation, or endovascular implantation of a left atrial occlusion device. Because atrial fibrillation-related stroke is preventable, a comparison of the value of these interventions by cost-effectiveness analysis (CEA) could inform clinical and health policy recommendations. In this article, we review the principles of CEA and identify 11 articles that examine CEA of stroke prophylaxis strategies in atrial fibrillation. Although most studies evaluate aspirin and warfarin across a variety of atrial fibrillation stroke risk profiles, we also review new literature on new pharmacologic therapies such as direct thrombin inhibitors and discuss the potential value of device-based therapies.