Objectives The aim of this study was to determine the risk of major clinical and thromboembolic events after cardioversion for atrial fibrillation in subjects treated with apixaban, an oral factor Xa ...inhibitor, compared with warfarin. Background In patients with atrial fibrillation, thromboembolic events may occur after cardioversion. This risk is lowered with vitamin K antagonists and dabigatran. Methods Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, we conducted a post-hoc analysis of patients undergoing cardioversion. Results A total of 743 cardioversions were performed in 540 patients: 265 first cardioversions in patients assigned to apixaban and 275 in those assigned to warfarin. The mean time to the first cardioversion for patients assigned to warfarin and apixaban was 243 ± 231 days and 251 ± 248 days, respectively; 75% of the cardioversions occurred by 1 year. Baseline characteristics were similar between groups. In patients undergoing cardioversion, no stroke or systemic emboli occurred in the 30-day follow-up period. Myocardial infarction occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Major bleeding occurred in 1 patient (0.2%) receiving warfarin and 1 patient receiving apixaban (0.3%). Death occurred in 2 patients (0.5%) receiving warfarin and 2 patients receiving apixaban (0.6%). Conclusions Major cardiovascular events after cardioversion of atrial fibrillation are rare and comparable between warfarin and apixaban. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ARISTOTLE; NCT00412984 )
Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). Few studies have compared clinical outcomes after catheter ablation between patients with and those without DM.
The ...purpose of this study was to compare AF ablation outcomes in patients with and those without DM.
We performed a retrospective analysis of 351 consecutive patients who underwent first-time AF ablation. Clinical outcomes included freedom from recurrent atrial arrhythmia, symptom burden (Mayo AF Symptom Inventory score), cardiovascular and all-cause hospitalizations, and periprocedural complications.
Patients with DM (n = 65) were older, had a higher body mass index, more persistent AF, more hypertension, and larger left atrial diameter (P <.05 for all). Median (Q1, Q3) total radiofrequency duration 64.0 (43.6, 81.4) minutes vs 54.3 (39.2, 76.4) minutes; P = .132 and periprocedural complications (P = .868) did not differ between patients with and those without DM. After a median follow-up of 29.5 months, arrhythmia recurrence was significantly higher in the DM group compared to the no-DM group after adjustment for baseline differences (adjusted hazard ratio HR 2.24; 95% confidence CI 1.42–3.55; P = .001). There was a nonsignificant trend toward higher AF recurrence with worse glycemic levels (HR 1.29; 95% CI 0.99–1.69; P = .064).
Although safety outcomes associated with AF ablation were similar between patients with and those without DM, arrhythmia-free survival was significantly lower among patients with DM. Poor glycemic control seems to an important risk factor for AF recurrence.
Background 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.
Atrial fibrillation (AF) is associated with increased risk of stroke that can be attenuated with vitamin K antagonists (VKAs). Vitamin K antagonist use is limited, in part, by the high incidence of ...complications when patients' international normalized ratios (INRs) deviate from the target range. The primary objective of ARISTOTLE is to determine if the factor Xa inhibitor, apixaban, is noninferior to warfarin at reducing the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism in patients with AF and at least 1 additional risk factor for stroke. We have randomized 18,206 patients from over 1,000 centers in 40 countries. Patients were randomly assigned in a 1:1 ratio to receive apixaban or warfarin using a double-blind, double-dummy design. International normalized ratios are monitored and warfarin (or placebo) is adjusted aiming for a target INR range of 2 to 3 using a blinded, encrypted point-of-care device. Minimum treatment is 12 months, and maximum expected exposure is 4 years. Time to accrual of at least 448 primary efficacy events will determine treatment duration. The key secondary objectives are to determine if apixaban is superior to warfarin for the combined endpoint of stroke (ischemic or hemorrhagic) and systemic embolism, and for all-cause death. These will be tested after the primary objective using a closed test procedure. The noninferiority boundary is 1.38; apixaban will be declared noninferior if the 95% CI excludes the possibility that the primary outcome rate with apixaban is >1.38 times higher than with warfarin. ARISTOTLE will determine whether apixaban is noninferior or superior to warfarin in preventing stroke and systemic embolism; whether apixaban has particular benefits in the warfarin-naïve population; whether it reduces the combined rate of stroke, systemic embolism, and death; and whether it impacts bleeding.
Abstract Background Patients with moderate-to-severe chronic kidney disease (CKD) are poorly represented in clinical trials of cardiac resynchronization therapy (CRT). Objectives This study sought to ...assess the real-world comparative effectiveness of CRT with defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) alone in CRT-eligible patients with moderate-to-severe CKD. Methods We conducted an inverse probability-weighted analysis of 10,946 CRT-eligible patients (ejection fraction <35%, QRS >120 ms, New York Heart Association functional class III/IV) with stage 3 to 5 CKD in the National Cardiovascular Data Registry (NCDR) ICD Registry, comparing outcomes between patients who received CRT-D (n = 9,525) versus ICD only (n = 1,421). Outcomes were obtained via Medicare claims and censored at 3 years. The primary endpoint of heart failure (HF) hospitalization or death and the secondary endpoint of death were assessed with Cox proportional hazards models. HF hospitalization, device explant, and progression to end-stage renal disease were assessed using Fine-Gray models. Results After risk adjustment, CRT-D use was associated with a reduction in HF hospitalization or death (hazard ratio HR: 0.84; 95% confidence interval CI: 0.78 to 0.91; p < 0.0001), death (HR: 0.85; 95% CI: 0.77 to 0.93; p < 0.0004), and HF hospitalization alone (subdistribution HR: 0.84; 95% CI: 0.76 to 0.93; p < 0.009). Subgroup analyses suggested that CRT was associated with a reduced risk of HF hospitalization and death across CKD classes. The incidence of in-hospital, short-term, and mid-term device-related complications did not vary across CKD stages. Conclusions In a nationally representative population of HF and CRT-eligible patients, use of CRT-D was associated with a significantly lower risk of the composite endpoint of HF hospitalization or death among patients with moderate-to-severe CKD in the setting of acceptable complication rates.
Background The benefit of a primary prevention implantable cardioverter-defibrillator (ICD) among patients with chronic kidney disease is uncertain. Study Design Meta-analysis of patient-level data ...from randomized controlled trials. Setting & Population Patients with symptomatic heart failure and left ventricular ejection fraction < 35%. Selection Criteria for Studies From 7 available randomized controlled studies with patient-level data, we selected studies with available data for important covariates. Studies without patient-level data for baseline estimated glomerular filtration rate (eGFR) were excluded. Intervention Primary prevention ICD versus usual care effect modification by eGFR. Outcomes Mortality, rehospitalizations, and effect modification by eGFR. Results We included data from the Multicenter Automatic Defibrillator Implantation Trial I (MADIT-I), MADIT-II, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). 2,867 patients were included; 36.3% had eGFR < 60 mL/min/1.73 m2 . Kaplan-Meier estimate of the probability of death during follow-up was 43.3% for 1,334 patients receiving usual care and 35.8% for 1,533 ICD recipients. After adjustment for baseline differences, there was evidence that the survival benefit of ICDs in comparison to usual care depends on eGFR (posterior probability for null interaction P < 0.001). The ICD was associated with survival benefit for patients with eGFR ≥ 60 mL/min/1.73 m2 (adjusted HR, 0.49; 95% posterior credible interval, 0.24-0.95), but not for patients with eGFR < 60 mL/min/1.73 m2 (adjusted HR, 0.80; 95% posterior credible interval, 0.40-1.53). eGFR did not modify the association between the ICD and rehospitalizations. Limitations Few patients with eGFR < 30 mL/min/1.73 m2 were available. Differences in trial-to-trial measurement techniques may lead to residual confounding. Conclusions Reductions in baseline eGFR decrease the survival benefit associated with the ICD. These findings should be confirmed by additional studies specifically targeting patients with varying eGFRs.
Background Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with ...more advanced heart failure (HF) derive ICD benefit owing to the competing risk of non-sudden death. Methods We performed a patient level meta-analysis of New York Heart Association class (NYHA) class II/III HF patients (left ventricular ejection fraction ≤35%) from 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT). Bayesian–Weibull survival regression models were employed to assess the impact of NYHA class on the relationship between ICD use and mortality. Results Of the 2763 patients who met study criteria, 68% (n = 1867) were NYHA II and 52% (n = 1435) were randomized to an ICD. In a multivariable model including all study patients, the ICD reduced mortality HR 0.65, 95% posterior credibility interval (PCI) 0.40–0.99. The interaction between NYHA class and the ICD on mortality was significant (posterior probability of no interaction = 0.036). In models including an interaction term for the NYHA class and ICD, the ICD reduced mortality among NYHA class II patients (HR 0.55, PCI 0.35–0.85) and the point estimate suggested reduced mortality in NYHA class III patients (HR 0.76, PCI 0.48–1.24) although this was not statistically significant. Conclusions Primary prevention ICDs reduce mortality in NYHA class II patients and trend towards reducing mortality in the heterogeneous group of NYHA class III patients. Improved risk stratification tools are required to guide patient selection and shared decision making among NYHA class III primary prevention ICD candidates.
Background There is no universally accepted algorithm for identifying atrial fibrillation (AF) patients and stroke risk using electronic data for use in performance measures. Methods Patients with AF ...seen in clinic were identified based on International Classification of Diseases, Ninth Revision (ICD-9) codes. CHADS2 and CHA2 DSs -Vasc scores were derived from a broad, 10-year algorithm using IICD-9 codes dating back 10 years and a restrictive, 1-year algorithm that required a diagnosis within the past year. Accuracy of claims-based AF diagnoses and of each stroke risk classification algorithm were evaluated using chart reviews for 300 patients. These algorithms were applied to assess system-wide anticoagulation rates. Results Between 6/1/2011, and 5/31/2012, we identified 6,397 patients with AF. Chart reviews confirmed AF or atrial flutter in 95.7%. A 1-year algorithm using CHA2 DS2 -Vasc score ≥2 to identify patients at risk for stroke maximized positive predictive value (97.5% negative predictive value 65.1%). The PPV of the 10-year algorithm using CHADS2 was 88.0%; 12% those identified as high-risk had CHADS2 scores <2. Anticoagulation rates were identical using 1-year and 10-year algorithms for patients with CHADS2 scores ≥2 (58.5% on anticoagulation) and CHA2 DS2 -Vasc scores ≥2 (56.0% on anticoagulation). Conclusions Automated methods can be used to identify patients with prevalent AF indicated for anticoagulation but may have misclassification up to 12%, which limits the utility of relying on administrative data alone for quality assessment. Misclassification is minimized by requiring comorbidity diagnoses within the prior year and using a CHA2 DS2-Vasc based algorithm. Despite differences in accuracy between algorithms, system-wide anticoagulation rates assessed were similar regardless of algorithm used.
Sotalol is a commonly prescribed antiarrhythmic drug (AAD) used for maintaining sinus rhythm in patients with atrial fibrillation (AF). Although randomized studies have found that sotalol can ...significantly delay time to AF recurrence, its association with mortality is less clear, particularly among those with coronary artery disease. We examined outcomes of 2,838 patients with coronary artery disease and AF. Using Cox proportional hazards modeling, landmark analysis, and time-dependent covariates for drug therapy, we compared cumulative survival among patients treated with sotalol (n = 226), amiodarone (n = 856), or no AAD (n = 1,756). Median follow-up was 4.2 years (interquartile range IQR 2.0–7.4). The median age was 68 years (IQR 60–75). Compared with those treated with amiodarone or no AAD, patients treated with sotalol were less likely to be black (6% vs 13% vs 13%) and have a previous myocardial infarction (35% vs 51% vs 48%) or a left ventricular ejection fraction <40% (13% vs 26% vs 21%). In follow-up, persistence of sotalol was limited; 97% of patients treated with sotalol were treated for <25% of the follow-up period. In adjusted analysis accounting for time on therapy, sotalol use was associated with an increased risk of all-cause death compared with no drug (hazard ratio 1.53, 95% confidence interval 1.19 to 1.96, p = 0.0009), but a decreased risk of death compared with amiodarone (hazard ratio 0.72, 95% confidence interval 0.55 to 0.91, p = 0.0141). In conclusion, sotalol therapy was more frequently used in patients with fewer co-morbidities, often discontinued early in follow-up, and was associated with increased mortality compared with no AAD but decreased mortality relative to amiodarone.
Little is known in clinical practice about antiarrhythmic drug (AAD) use in patients with atrial fibrillation (AF) (particularly younger ones) who do not have structural heart disease. Using the ...MarketScan database, we identified patients <65 years without known coronary artery disease or heart failure who had an AAD prescription claim (class Ic drug, amiodarone, sotalol, or dronedarone) after their first AF encounter. A multinomial logistic regression model was created to assess factors associated with using each available AAD compared with using class Ic drugs before and after dronedarone was marketed in the United States. Additionally, we used the Kaplan-Meier method to determine the rates of change in AAD use and discontinuation during the year after AAD initiation. Of 8,562 patients with AF, 35% received class Ic drugs, 34% amiodarone, 24% sotalol, and 7% dronedarone. The median patient age was 56 (interquartile range 49 to 61), and 34% were women. Both before and after dronedarone was marketed, there was a statistically significant lower likelihood of class Ic drug use versus other AAD use with increasing age, inpatient index AF encounter, and previous or concomitant anticoagulation therapy. During the 1 year after AAD initiation, the AAD change rate was 14% for class Ic drugs, 8% for amiodarone, 17% for sotalol, and 18% for dronedarone (p <0.001); the AAD discontinuation rate was 40% for class Ic drugs, 52% for amiodarone, 40% for sotalol, and 69% for dronedarone (p <0.001). In conclusion, we found extensive use of amiodarone that may be inconsistent with guideline recommendations and unexpectedly high rates of AAD discontinuation.
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