Sean D. Pokorney

Patients’ time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF registry

BACKGROUND Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR among patients with atrial fibrillation (AF) in community-based clinical practice. METHODS Using the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we examined TTR (using a modified Rosendaal method) among 5,210 patients with AF on warfarin and treated at 155 sites. Patients were grouped into quartiles based on TTR data. Multivariable logistic regression modeling with generalized estimating equations was used to determine patient and provider factors associated with the lowest (worst) TTR. RESULTS Overall, 59% of the measured INR values were between 2.0 and 3.0, with an overall mean and median TTR of 65% ± 20% and 68% (interquartile range [IQR] 53%-79%). The median times below and above the therapeutic range were 17% (IQR 8%-29%) and 10% (IQR 3%-19%), respectively. Patients with renal dysfunction, advanced heart failure, frailty, prior valve surgery, and higher risk for bleeding (ATRIA score) or stroke (CHA2DS2-VASc score) had significantly lower TTR (P < .0001 for all). Patients treated at anticoagulation clinics had only slightly higher median TTR (69%) than those not (66%) (P < .0001). CONCLUSIONS Among patients with AF in US clinical practices, TTR on warfarin is suboptimal, and those at highest predicted risks for stroke and bleeding were least likely to be in therapeutic range.

Cause of Death and Predictors of All‐Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation: Data From ROCKET AF

Background Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions. Methods and Results In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677). Conclusions In a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Digoxin use and subsequent outcomes among patients in a contemporary atrial fibrillation cohort

BACKGROUND Although digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial. OBJECTIVES This study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF, to characterize the predictors of digoxin use and initiation, and to correlate digoxin use with outcomes. METHODS Longitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011. RESULTS Among 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) received digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. After adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers (p < 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity adjusted HR: 1.05), but was associated with subsequent death in those without HF (propensity adjusted HR: 1.99). CONCLUSIONS After adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Because of the multiple conflicting observational reports about digoxins safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed.

Implantable Cardioverter-Defibrillator Use Among Medicare Patients With Low Ejection Fraction After Acute Myocardial Infarction.

IMPORTANCE Implantable cardioverter-defibrillators (ICDs) are not recommended within 40 days of myocardial infarction (MI); thus, ICD implantation might not be considered during the post-MI care transition. OBJECTIVE To examine ICD implantation rates and associated mortality among older MI patients with low ejection fraction (EF). DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of Medicare beneficiaries with an EF of 35% or less after MI, treated at 441 US hospitals between 2007 and 2010, excluding patients with prior ICD implantation. Follow-up data were available through December 2010. EXPOSURES ICD implantation within 1 year of MI vs no ICD implantation within 1 year of MI. MAIN OUTCOMES AND MEASURES Patient characteristics associated with receiving an ICD within 1 year after discharge and 2-year mortality associated with ICD implantation. RESULTS Among 10,318 MI patients with EF of 35%or lower, the cumulative 1-year ICD implantation rate was 8.1% (95%CI, 7.6%-8.7%). Patients with ICD implantation were more likely to have prior coronary artery bypass graft procedures, higher peak troponin levels, in-hospital cardiogenic shock, and cardiology follow-up within 2 weeks after discharge relative to patients who did not receive an ICD within 1 year. Implantation of ICD was associated with lower 2-year mortality (15.3 events per 100 patient-years [128 deaths in 838 patient-years] vs 26.4 events per 100 patient-years [3033 deaths in 11 479 patient-years]; adjusted HR, 0.64; 95%CI, 0.53-0.78). [table: see text] CONCLUSIONS AND RELEVANCE In this large registry study of older patients who experienced MI from 2007-2010, fewer than 1 in 10 eligible patients with low EF received an ICD within 1 year after MI, although ICD implantation was associated with lower risk-adjusted mortality at 2 years. Additional research is needed to determine evidence-based approaches to increase ICD implantation among eligible patients.

Stability of International Normalized Ratios in Patients Taking Long-term Warfarin Therapy.

Stability of International Normalized Ratios in Patients Taking Long-term Warfarin Therapy Warfarin substantially decreases stroke risk among patients with atrial fibrillation yet has a narrow therapeutic window (international normalized ratio [INR] values of 2.0-3.0) and is associated with multiple drug and food interactions.1 Non– vitamin K oral anticoagulants do not require drug monitoring and have similar or improved safety and efficacy relative to warfarin but are more costly.2 Whether patients previously stable on warfarin should be switched to non–vitamin K oral anticoagulants remains controversial but may be informed by determining whether patients receiving warfarin who have stable INR values remain stable over time. Methods | Written informed consent was obtained for registry enrollment. The Duke institutional review board approved this study. Data were obtained from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, a prospective registry of patients with atrial fibrillation from 176 clinics who were enrolled June 2010 through August 2011 and followed up for 3 years through November 2014.3 Patients receiving warfarin at baseline with 3 or more INR values in the first 6 months and 6 or more in the subsequent year were included. Stability was defined as 80% or more INRs in therapeutic range (2.0-3.0). An R2 value assessed stability in the first 6 months as a predictor of stability in the subsequent year (both continuous). A C index determined whether stable INR during the baseline 6 months discriminated stable INR in the subsequent year.

Clinical strategies for selecting oral anticoagulants in patients with atrial fibrillation

Atrial fibrillation is a common arrhythmia. One of the important aspects of the management of atrial fibrillation is stroke prevention. Warfarin has been the longstanding anticoagulant used for stroke prevention in patients with atrial fibrillation. There are now three novel oral anticoagulants, which have been studied in randomized controlled trials and subsequently approved by the Federal Drug Administration for stroke prevention in patients with atrial fibrillation. Special patient populations, including renal insufficiency, elderly, prior stroke, and extreme body weights, were represented to varying degrees in the clinical trials of the novel oral anticoagulants. Furthermore, there is variation in the pharmacokinetics and pharmacodynamics of each anticoagulant, which affect the patient populations differently. Patients and clinicians are faced with the task of selecting among the available anticoagulants, and this review is designed to be a tool for clinical decision-making.

Cable externalization and electrical failure of the Riata family of implantable cardioverter-defibrillator leads: A systematic review and meta-analysis.

BACKGROUND The Riata class of defibrillator leads were placed under US Food and Drug Association (FDA) advisory as of November 2011 because of high rates of cable externalization (CE) and electrical failure (EF). The overall rates of these complications remain unknown. OBJECTIVE The purpose of this study was to systematically search the literature for rates of Riata lead failure and to perform a meta-analysis to estimate failure rates. METHODS We conducted a meta-analysis of observational studies examining the rates of EF, CE, and the interaction of the two. We identified 23 English language manuscripts addressing 1 or more of these questions. RESULTS Across 23 studies, the overall CE rate was 23.1% (95% confidence interval [CI] 19.0%-27.6%). The overall EF rate was 6.3% (95% CI 4.7%-8.2%). The presence of CE was associated with a more than 6-fold increase in the rate of EF compared to no CE (17.3% [95% CI 11.2%-25.9%] vs 2.7% [95% CI 1.4%-5.2%], respectively). The rate of CE was 3-fold higher for 8Fr leads compared to 7Fr leads, but rates of EF were similar (4.6%; 95% CI 3.2-6.6] and 3.9%; 95% CI 2.4-6.1], respectively). Rates of both CE and EF were higher in dual coil vs single coil leads, but confidence intervals overlapped. CONCLUSION In clinical practice, rates of CE in Riata leads are substantial. While CE is associated with a significant increase in the risk of EF, the incidence of EF without externalization is not trivial.

Incidence and predictors of appropriate therapies delivered by the implantable cardioverter defibrillator in patients with ischemic cardiomyopathy: A systematic review

BACKGROUND Although the implantable cardioverter defibrillator (ICD) improves the survival of patients at increased risk of sudden cardiac death due to systolic heart failure, ICD shocks have been associated with both worse survival and quality of life. We performed a systematic review of primary prevention ICD studies to evaluate the incidence and clinical predictors of appropriate ICD shocks or anti-tachycardia pacing (ATP) in patients with ischemic cardiomyopathy. METHODS We performed a literature search in MEDLINE. Eligible studies had to be full text, written in the English language, performed in adults aged ≥ 19, and published from 1999 through April 2014. RESULTS Of 289 identified studies, 9 met all our inclusion criteria. The mean length of follow up ranged from 17 to 45.5 months. The incidence of appropriate ICD therapy varied from 17% to 31%. Among those studies, only 4 included data on the clinical characteristics of appropriate ICD therapy recipients. Characteristics associated with appropriate ICD therapy included male sex, advanced New York Heart Association class, non-sustained ventricular tachycardia, and lower serum creatinine. Patients who received appropriate therapy were also less likely to be on a beta-blocker. Left ventricular ejection fraction was not significantly different between patients who received appropriate ICD therapy and those who did not. CONCLUSION The incidence of appropriate ICD therapy is not trivial in patients with ischemic cardiomyopathy and a primary prevention ICD. Predictors of appropriate ICD therapy have not been adequately assessed in large patient populations. As such, large prospective studies of predictors of appropriate ICD therapies are needed.

Cognitive Function: Is There More to Anticoagulation in Atrial Fibrillation Than Stroke?

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and those afflicted have reduced quality of life, functional status, and cardiac performance.[1][1] Patients with AF have a higher risk of stroke, heart failure, and premature death relative to patients without AF.[2][2] It is estimated

High-degree atrioventricular block, asystole, and electro-mechanical dissociation complicating non–ST-segment elevation myocardial infarction

UNLABELLED Non-ST-segment myocardial infarction (NSTEMI) can be complicated by high-degree atrioventricular (AV) block, asystole, or electromechanical dissociation (EMD), but these events are not well characterized in the contemporary era. This analysis assesses the incidence of and factors associated with these dysrhythmias in acute NSTEMIs. METHODS Patients with NSTEMI in the EARLY ACS, PLATO, and TRACER trials were included in the pooled cohort (N = 29,677). Logistic regression was used to identify factors associated with in-hospital high-degree AV block and asystole or EMD, and Kaplan-Meier methods were used to assess mortality. RESULTS High-degree AV block occurred in 112 (0.4%) patients, asystole in 157 (0.5%), and EMD in 38 (0.1%). Pacemakers were inserted in 241 patients (0.8%) during the index hospitalization: 30 (12%) for AV block. Among patients with high-degree AV block, we observed more frequent right coronary artery lesions (47% vs 29%). Age, diabetes, lower heart rate, and lower blood pressure were associated with high-degree AV block. Higher Killip class, ST-segment depression, prior myocardial infarction, and peripheral vascular disease were most strongly associated with asystole or EMD. Ten-day unadjusted survival was 90% for patients with high-degree AV block and 43% for those with asystole or EMD. CONCLUSIONS Although high-degree AV block, asystole, and EMD were infrequent complications of NSTEMI, they were associated with substantial short-term mortality. Only 1 in 8 pacemakers placed in NSTEMI patients during the acute hospitalization was for high-degree AV block.