Laura G. Qualls

Associations Between Aldosterone Antagonist Therapy and Risks of Mortality and Readmission Among Patients With Heart Failure and Reduced Ejection Fraction

CONTEXT Aldosterone antagonist therapy for heart failure and reduced ejection fraction has been highly efficacious in randomized trials. However, questions remain regarding the effectiveness and safety of the therapy in clinical practice. OBJECTIVE To examine the clinical effectiveness of newly initiated aldosterone antagonist therapy among older patients hospitalized with heart failure and reduced ejection fraction. DESIGN, SETTING, AND PARTICIPANTS Using clinical registry data linked to Medicare claims from 2005 through 2010, we examined outcomes of eligible patients hospitalized with heart failure and reduced ejection fraction. We used Cox proportional hazards models and inverse-weighted estimates of the probability of treatment to adjust for treatment selection bias. MAIN OUTCOME MEASURES All-cause mortality, cardiovascular readmission, and heart failure readmission at 3 years, and hyperkalemia readmission at 30 days and 1 year. RESULTS Among 5887 patients who met the inclusion criteria, the mean age was 77.6 years; of those 1070 (18.2%) started aldosterone antagonist therapy at discharge. Cumulative incidence rates among treated and untreated patients were 49.9% vs 51.2% (P = .62) for mortality; 63.8% vs 63.9% (P = .65) for cardiovascular readmission; and 38.7% vs 44.9% (P < .001) for heart failure readmission at 3 years; and 2.9% vs 1.2% (P < .001) for hyperkalemia readmission within 30 days and 8.9% vs 6.3% (P = .002) within 1 year. After inverse weighting for the probability of treatment, there were no significant differences in mortality (hazard ratio [HR], 1.04; 95% CI, 0.96-1.14; P = .32) and cardiovascular readmission (HR, 1.00; 95% CI, 0.91-1.09; P = .94). Heart failure readmission was lower among treated patients at 3 years (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Readmission associated with hyperkalemia was higher with aldosterone antagonist therapy at 30 days (HR, 2.54; 95% CI, 1.51-4.29; P < .001) and 1 year (HR, 1.50; 95% CI, 1.23-1.84; P < .001). CONCLUSIONS Initiation of aldosterone antagonist therapy at hospital discharge was not independently associated with improved mortality or cardiovascular readmission but was associated with improved heart failure readmission among eligible older patients with heart failure and reduced ejection fraction. There was a significant increase in the risk of readmission with hyperkalemia, predominantly within 30 days after discharge.

QRS Duration, Bundle-Branch Block Morphology, and Outcomes Among Older Patients With Heart Failure Receiving Cardiac Resynchronization Therapy

IMPORTANCE The benefits of cardiac resynchronization therapy (CRT) in clinical trials were greater among patients with left bundle-branch block (LBBB) or longer QRS duration. OBJECTIVE To measure associations between QRS duration and morphology and outcomes among patients receiving a CRT defibrillator (CRT-D) in clinical practice. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of Medicare beneficiaries in the National Cardiovascular Data Registrys ICD Registry between 2006 and 2009 who underwent CRT-D implantation. Patients were stratified according to whether they were admitted for CRT-D implantation or for another reason, then categorized as having either LBBB or no LBBB and QRS duration of either 150 ms or greater or 120 to 149 ms. MAIN OUTCOMES AND MEASURES All-cause mortality; all-cause, cardiovascular, and heart failure readmission; and complications. Patients underwent follow-up for up to 3 years, with follow-up through December 2011. RESULTS Among 24 169 patients admitted for CRT-D implantation, 1-year and 3-year mortality rates were 9.2% and 25.9%, respectively. All-cause readmission rates were 10.2% at 30 days and 43.3% at 1 year. Both the unadjusted rate and adjusted risk of 3-year mortality were lowest among patients with LBBB and QRS duration of 150 ms or greater (20.9%), compared with LBBB and QRS duration of 120 to 149 ms (26.5%; adjusted hazard ratio [HR], 1.30 [99% CI, 1.18-1.42]), no LBBB and QRS duration of 150 ms or greater (30.7%; HR, 1.34 [99% CI, 1.20-1.49]), and no LBBB and QRS duration of 120 to 149 ms (32.3%; HR, 1.52 [99% CI, 1.38-1.67]). The unadjusted rate and adjusted risk of 1-year all-cause readmission were also lowest among patients with LBBB and QRS duration of 150 ms or greater (38.6%), compared with LBBB and QRS duration of 120 to 149 ms (44.8%; adjusted HR, 1.18 [99% CI, 1.10-1.26]), no LBBB and QRS duration of 150 ms or greater (45.7%; HR, 1.16 [99% CI, 1.08-1.26]), and no LBBB and QRS duration of 120 to 149 ms (49.6%; HR, 1.31 [99% CI, 1.23-1.40]). There were no observed associations with complications. CONCLUSIONS AND RELEVANCE Among fee-for-service Medicare beneficiaries undergoing CRT-D implantation in clinical practice, LBBB and QRS duration of 150 ms or greater, compared with LBBB and QRS duration less than 150 ms or no LBBB regardless of QRS duration, was associated with lower risk of all-cause mortality and of all-cause, cardiovascular, and heart failure readmissions.

Treatment Patterns for Neovascular Age-Related Macular Degeneration: Analysis of 284 380 Medicare Beneficiaries

PURPOSE To examine trends in the treatment of newly diagnosed neovascular age-related macular degeneration (AMD). DESIGN Retrospective cohort study. METHODS Among 284 380 Medicare beneficiaries with a new diagnosis between 2006 and 2008, we used the cumulative incidence function to estimate procedure rates and the mean frequency function to estimate the cumulative mean number of intravitreous injections. We used Cox log-binomial regression to estimate predictors of the use of vascular endothelial growth factor (VEGF) antagonists within 1 year after diagnosis. Discontinuation of anti-VEGF therapy was defined by absence of treatment for 12 months. Discontinuation rates were calculated using the Kaplan-Meier method. RESULTS The proportion of patients receiving anti-VEGF therapy increased from 60.3% to 72.7%, photodynamic therapy decreased from 12.8% to 5.3%, and thermal laser treatment decreased from 5.5% to 3.2%. Black patients (hazard ratio, 0.77; 95% confidence interval, 0.75-0.79) and patients of other/unknown race (0.83; 0.81-0.84) were less likely than white patients to receive anti-VEGF therapy. Patients with dementia were less likely to receive anti-VEGF therapy (0.88; 0.88-0.89). Among patients who received anti-VEGF therapy, the mean number of injections within 1 year of the first injection was 4.3 per treated eye. Anti-VEGF therapy was discontinued in 53.6% of eyes within 1 year, and in 61.7% of eyes within 18 months. CONCLUSIONS Treatment of new neovascular AMD changed significantly between 2006 and 2008, most notably in the increasing use of anti-VEGF therapies. However, few patients treated with anti-VEGF medications received monthly injections, and discontinuation rates were high.

Outcomes of medicare beneficiaries with heart failure and atrial fibrillation.

OBJECTIVES This study sought to examine the long-term outcomes of patients hospitalized with heart failure and atrial fibrillation. BACKGROUND Atrial fibrillation is common among patients hospitalized with heart failure. Associations of pre-existing and new-onset atrial fibrillation with long-term outcomes are unclear. METHODS We analyzed 27,829 heart failure admissions between 2006 and 2008 at 281 hospitals in the American Heart Associations Get With The Guidelines-Heart Failure program linked with Medicare claims. Patients were classified as having pre-existing, new-onset, or no atrial fibrillation. Cox proportional hazards models were used to identify factors that were independently associated with all-cause mortality, all-cause readmission, and readmission for heart failure, stroke, and other cardiovascular disease at 1 and 3 years. RESULTS After multivariable adjustment, pre-existing atrial fibrillation was associated with greater 3-year risks of all-cause mortality (hazard ratio [HR]: 1.14 [99% confidence interval (CI): 1.08 to 1.20]), all-cause readmission (HR: 1.09 [99% CI: 1.05 to 1.14]), heart failure readmission (HR: 1.15 [99% CI: 1.08 to 1.21]), and stroke readmission (HR: 1.20 [99% CI: 1.01 to 1.41]), compared with no atrial fibrillation. There was also a greater hazard of mortality at 1 year among patients with new-onset atrial fibrillation (HR: 1.12 [99% CI: 1.01 to 1.24]). Compared with no atrial fibrillation, new-onset atrial fibrillation was not associated with a greater risk of the readmission outcomes. Stroke readmission rates at 1 year were just as high for patients with preserved ejection fraction as for patients with reduced ejection fraction. CONCLUSIONS Both pre-existing and new-onset atrial fibrillation were associated with greater long-term mortality among older patients with heart failure. Pre-existing atrial fibrillation was associated with greater risk of readmission.

Transitional adherence and persistence in the use of aldosterone antagonist therapy in patients with heart failure

BACKGROUND Aldosterone antagonist therapy is recommended for selected patients with heart failure and reduced ejection fraction. Adherence to therapy in the transition from hospital to home is not well understood. METHODS We identified patients with heart failure and reduced ejection fraction who were ≥65 years old, eligible for aldosterone antagonist therapy, and discharged home from hospitals in the Get With the Guidelines-Heart Failure registry between January 1, 2005, and December 31, 2008. We used Medicare prescription drug event data to measure adherence. Main outcome measures were prescription at discharge, outpatient prescription claim within 90 days, discontinuation, and adherence as measured with the medication possession ratio. We used the cumulative incidence function to estimate rates of initiation and discontinuation. RESULTS Among 2,086 eligible patients, 561 (26.9%) were prescribed an aldosterone antagonist at discharge. Within 90 days, 78.6% of eligible patients with a discharge prescription filled a prescription for the therapy, compared with 13.0% of eligible patients without a discharge prescription (P < .001). The median medication possession ratio was 0.63 over 1 year of follow-up. Among 634 patients who filled a prescription within 90 days of discharge, 7.9% discontinued therapy within 1 year. CONCLUSION Most eligible patients were not prescribed aldosterone antagonist therapy at discharge from a heart failure hospitalization. Eligible patients without a discharge prescription seldom initiated therapy as outpatients. Most patients who were prescribed an aldosterone antagonist at discharge filled the prescription within 90 days and remained on therapy.

In-Hospital Worsening Heart Failure and Associations With Mortality, Readmission, and Healthcare Utilization

Background A subset of patients hospitalized with acute heart failure experiences worsening clinical status and requires escalation of therapy. Worsening heart failure is an end point in many clinical trials, but little is known about its prevalence in clinical practice and its associated outcomes. Methods and Results We analyzed inpatient data from the Acute Decompensated Heart Failure National Registry linked to Medicare claims to examine the prevalence and outcomes of patients with worsening heart failure, defined as the need for escalation of therapy at least 12 hours after hospital presentation. We compared patients with worsening heart failure to patients with an uncomplicated hospital course and patients with a complicated presentation. Of 63 727 patients hospitalized with acute heart failure, 11% developed worsening heart failure. These patients had the highest observed rates of mortality, all‐cause readmission, and Medicare payments at 30 days and 1 year after hospitalization (P < 0.001 for all comparisons). The adjusted hazards of 30‐day mortality were 2.56 (99% CI, 2.34 to 2.80) compared with an uncomplicated course and 1.29 (99% CI, 1.17 to 1.42) compared with a complicated presentation. The adjusted cost ratios for postdischarge Medicare payments at 30 days were 1.35 (99% CI, 1.24 to 1.46) compared with an uncomplicated course and 1.11 (99% CI, 1.02 to 1.22) compared with a complicated presentation. Conclusions In‐hospital worsening heart failure was common and was associated with higher rates of mortality, all‐cause readmission, and postdischarge Medicare payments. Prevention and treatment of in‐hospital worsening heart failure represents an important goal for patients hospitalized with acute heart failure.

Anti-VEGF treatment patterns for neovascular age-related macular degeneration among medicare beneficiaries.

PURPOSE To examine the use of anti-vascular endothelial growth factor (VEGF) therapy in clinical practice among patients with neovascular age-related macular degeneration (AMD). DESIGN Retrospective cohort study. METHODS Among 459 237 Medicare beneficiaries, we identified anti-VEGF treatment using claims for intravitreal injections of anti-VEGF medications with a supporting diagnosis of neovascular AMD. We used the cumulative incidence function to calculate the frequency of anti-VEGF treatments and treatment visits for neovascular AMD per treated eye in the first and second year after the initial anti-VEGF injection. We calculated the mean number of treatments and treatment visits per eye using the mean frequency function. Rates of discontinuation were estimated using Kaplan-Meier methods. RESULTS The mean number of injections was 4.3 in the first year, with 58% of patients receiving 1-4 injections, 20% receiving 5-6 injections, and 22% receiving 7 or more injections. Among patients who received 7 or more injections during the first year, 31% received a comparable number during the second year, and 12% received no injections. Of patients who received 1-4 injections during the first year, 70% received no injections and 24% received 1-4 injections during the second year. Rates of anti-VEGF discontinuation were 57% within 12 months and 71% within 24 months. CONCLUSIONS The frequency of anti-VEGF injections for neovascular AMD was lower than that recommended by large-scale clinical trials, and rates of discontinuation were high. National practice patterns in anti-VEGF therapy for patients with neovascular AMD do not reflect optimal treatment strategies suggested by recent clinical trial evidence.

Follow-up of patients with new cardiovascular implantable electronic devices: are experts' recommendations implemented in routine clinical practice?

Background— A 2008 expert consensus statement outlined the minimum frequency of follow-up of patients with cardiovascular implantable electronic devices (CIEDs). Methods and Results— We studied 38 055 Medicare beneficiaries who received a new CIED between January 1, 2005, and June 30, 2009. The main outcome measure was variation of follow-up by patient factors and year of device implantation. We determined the number of patients who were eligible for and attended an in-person CIED follow-up visit within 2 to 12 weeks, 0 to 16 weeks, and 1 year after implantation. Among eligible patients, 42.4% had an initial in-person visit within 2 to 12 weeks. This visit was significantly more common among white patients than black patients and patients of other races (43.0% versus 36.8% versus 40.5%; P <0.001). Follow-up within 2 to 12 weeks improved from 40.3% in 2005 to 55.1% in 2009 ( P <0.001 for trend). The rate of follow-up within 0 to 16 weeks was 65.1% and improved considerably from 2005 to 2009 (62.3%–79.6%; P <0.001 for trend). Within 1 year, 78.0% of the overall population had at least 1 in-person CIED follow-up visit. Conclusions— Although most Medicare beneficiaries who received a new CIED between 2005 and 2009 did not have an initial in-person CIED follow-up visit within 2 to 12 weeks after device implantation, the rate of initial follow-up improved appreciably over time. This CIED follow-up visit was significantly more common in white patients than in patients of other races.Background—A 2008 expert consensus statement outlined the minimum frequency of follow-up of patients with cardiovascular implantable electronic devices (CIEDs). Methods and Results—We studied 38 055 Medicare beneficiaries who received a new CIED between January 1, 2005, and June 30, 2009. The main outcome measure was variation of follow-up by patient factors and year of device implantation. We determined the number of patients who were eligible for and attended an in-person CIED follow-up visit within 2 to 12 weeks, 0 to 16 weeks, and 1 year after implantation. Among eligible patients, 42.4% had an initial in-person visit within 2 to 12 weeks. This visit was significantly more common among white patients than black patients and patients of other races (43.0% versus 36.8% versus 40.5%; P<0.001). Follow-up within 2 to 12 weeks improved from 40.3% in 2005 to 55.1% in 2009 (P<0.001 for trend). The rate of follow-up within 0 to 16 weeks was 65.1% and improved considerably from 2005 to 2009 (62.3%–79.6%; P<0.001 for trend). Within 1 year, 78.0% of the overall population had at least 1 in-person CIED follow-up visit. Conclusions—Although most Medicare beneficiaries who received a new CIED between 2005 and 2009 did not have an initial in-person CIED follow-up visit within 2 to 12 weeks after device implantation, the rate of initial follow-up improved appreciably over time. This CIED follow-up visit was significantly more common in white patients than in patients of other races.

Early intravenous heart failure therapy and outcomes among older patients hospitalized for acute decompensated heart failure: Findings from the Acute Decompensated Heart Failure Registry Emergency Module (ADHERE-EM)

BACKGROUND Timing of initial treatment for acute decompensated heart failure (ADHF) varies across hospitals and its impact on outcomes remains poorly defined. We examined the association between time to first intravenous (IV) heart failure (HF) therapy and patient outcomes. METHODS Using the ADHERE-EM linked to Medicare claims data, we identified patients ≥65 years old who were hospitalized for ADHF and received IV HF therapy during index admission. Cox proportional hazard model was used to assess the association of time to treatment with a composite of 30-day all-cause mortality or re-admission. Generalized linear mixed models were used to examine the association of time to treatment with in-hospital all-cause mortality, index hospitalization length of stay, and total days alive and out-of-hospital at 30 days. RESULTS Of 6,971 patients, the median time to first IV HF therapy was 2.3-hours (interquartile range 1.1, 4.4). The cumulative incidence of 30-day all-cause mortality or readmission was 27.4%. After adjusting for covariates, time to treatment was not associated with increased risk of composite 30-day all-cause mortality or re-admission (HR 1.00; 95% CI 1.00-1.00; P = .221). However, every hour delay in treatment was associated with a modest increased risk of in-hospital mortality (adjusted OR 1.01; 95% CI 1.00-1.02; P = .001) and an approximately 1.4-hour increase in index admission length of stay (P < .001). CONCLUSION Among older patients presenting with ADHF, delay in initiating IV HF therapy was associated with modestly higher risk for in-hospital mortality and longer length of stay, but was not associated with 30-day outcomes.

Comparative effectiveness of cardiac resynchronization therapy with an implantable cardioverter-defibrillator versus defibrillator therapy alone: a cohort study.

Context In randomized, controlled trials, cardiac resynchronization therapy with a defibrillator (CRT-D) decreased mortality in patients with reduced left ventricular ejection fraction and prolonged QRS duration compared with implantable cardioverter-defibrillator (ICD) therapy alone. The relative benefits and harms of these devices in more routine practice settings have not been studied. Contribution The investigators compared CRT-D with ICD in more than 7000 patients enrolled in a patient registry and found that CRT-D decreased mortality more than ICD. Device-related infections were more common with CRT-D. Caution Residual confounding could not be eliminated. Implication Real-world performance of CRT-D versus ICD seems similar to that observed in randomized, controlled trials. The Editors Implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) have changed the management of patients with reduced left ventricular ejection faction (LVEF). Guidelines for device-based treatment recommend ICD therapy for many patients with reduced LVEF (1) on the basis of randomized, controlled trials showing mortality benefits of ICD therapy (27). Cardiac resynchronization therapy with an ICD (CRT-D), which involves the placement of an additional coronary sinus lead capable of pacing the left ventricle, is further recommended for selected patients with an LVEF of 0.35 or less, heart failure, and evidence of ventricular dyssynchrony manifested as QRS prolongation on electrocardiography (1). The recommendations are based on evidence of lower risk for worsening heart failure and, in some cases, lower mortality with CRT-D in these selected groups (1). Although randomized clinical trials have identified important incremental benefits of CRT in selected patients, the comparative effectiveness of CRT-D versus ICD therapy has not been characterized in patients cared for in clinical practice. Clinical trials in patients with cardiovascular disease in general (8, 9) and of device therapy in particular (10, 11) have typically enrolled selected patients who differ from those seen in practice. Device trials are also often performed in sites and by clinicians with substantial expertise, which may reduce complication rates (12). This factor is specifically germane to CRT because implanting the additional left ventricular lead is associated with higher rates of complications than ICD therapy alone (13). Differences in the patients selected for therapy and the centers where the procedures are done could influence the outcomes of device therapy in real-world clinical practice. Given the number of ICD and CRT devices implanted in the United States annually (14), understanding the incremental effectiveness and complications of CRT in patients treated in contemporary practice could have important implications for patients, clinicians, and policymakers. Controversies about the optimum use of CRT persist. Although the benefits are clearest and recommendations for its use are strongest in patients with left bundle branch block (LBBB) and a QRS duration greater than 150 ms, the benefits in patients with other intraventricular conduction delays (for example, right bundle branch block) and less prolonged QRS duration are debated (1). Furthermore, the benefits of CRT have generally been greatest in patients with more severe symptoms of heart failure, but recent trials have suggested meaningful benefits in less symptomatic patients (6, 7, 15). Finally, questions about the effectiveness of CRT according to patient sex (6, 16) or in patients with atrial fibrillation (1) have been raised. We performed an observational comparative effectiveness study of CRT-D versus ICD therapy alone in a contemporary cohort of patients with reduced LVEF and electrocardiographic evidence of ventricular dyssynchrony who were receiving device-based therapy. Our objectives were to characterize the associations between CRT-D versus ICD therapy alone and patient outcomes, including death, hospitalizations, and device-related complications, and to investigate these associations in specific subgroups of clinical interest. Methods Data Sources Data were from the National Cardiovascular Data Registrys ICD Registry and the Centers for Medicare & Medicaid Services Medicare claims data. The ICD Registry was established in 2005 through a partnership of the Heart Rhythm Society and the American College of Cardiology Foundation and became the sole repository of ICD implantation data for Medicare beneficiaries on 1 April 2006. The Centers for Medicare & Medicaid Services mandates that hospitals enter data on all Medicare beneficiaries receiving ICD therapy for primary prevention into the registry (14), which contains patient demographic characteristics, detailed medical history, and clinical and procedural information. The registry uses standardized data definitions and data quality monitoring (17). Medicare data include inpatient and outpatient claims and the corresponding denominator files between 2006 and 2011. We linked the registry data to Medicare claims data using a validated method that involves combinations of indirect identifiers (18). The Institutional Review Board of the Duke University Health System (Durham, North Carolina) approved the study. Study Cohort In the linked data set, we identified patients who were 65 years or older; were admitted specifically for first-time device implantation; were discharged home between 1 April 2006 and 31 December 2009; were enrolled in fee-for-service Medicare at discharge; and might be considered for CRT-D on the basis of a history of heart failure, an LVEF of 0.35 or less, and a QRS duration at least 120 ms. We excluded patients who received device therapy for secondary prevention, received epicardial leads, were admitted for reasons other than device implantation, had coronary revascularization during the index admission, had a prior ICD pacemaker, or had myocardial infarction within 40 days before the index discharge. Treatment The treatments of interest were CRT-D and ICD therapy alone as recorded in the registry. The registry does not include data for patients receiving CRT without a defibrillator; thus, this therapy was not considered. Outcomes The outcomes of interest were the occurrence of and time to all-cause mortality; all-cause readmission; and readmission for cardiovascular disease, heart failure, device-related infection, and mechanical complications requiring system revision for up to 3 years after implantation. We ascertained mortality on the basis of death dates in the Medicare denominator files and readmission on the basis of subsequent Medicare inpatient claims (Appendix Table 1). Appendix Table 1. Definitions of Readmission Outcomes Subgroups We prespecified clinically important subgroupsincluding age, sex, race, and type of intraventricular conduction delaycombined with QRS duration, New York Heart Association class, and the presence or absence of atrial fibrillation and renal dysfunction. We also considered subgroups according to the cause of left ventricular systolic dysfunction (ischemic vs. nonischemic). We combined the type of intraventricular conduction delay and QRS duration and classified patients into 1 of 4 categories according to guidelines for device-based therapy: LBBB and QRS duration 150 ms or greater, LBBB and QRS duration 120 to 149 ms, no LBBB and QRS duration 150 ms or greater, and no LBBB and QRS duration 120 to 149 ms (1). For the purposes of subgroup analysis, we categorized renal function into 4 groups on the basis of estimated glomerular filtration rates of 90 mL/min/1.73 m2 or greater, 60 to 89 mL/min/1.73 m2, 30 to 59 mL/min/1.73 m2, and 29 mL/min/1.73 m2 or less or end-stage renal disease (19). Covariates We obtained covariates of interest from the registry, including demographic characteristics, medical history, results of clinical measures, year of implantation, and discharge medications. We considered patients to be receiving optimal medical therapy if they received a -blocker and an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker in the absence of contraindications. Demographic variables were complete, and the other variables were missing at low rates (<1%). To avoid case-wise deletions, we imputed missing continuous variables to the overall median value and missing categorical variables to the most common response, an approach that is considered appropriate for variables with low rates of missing data (20). Statistical Analysis We described the baseline characteristics of the study population by using frequencies with percentages for categorical variables and means with SDs for continuous variables. We tested for differences between treatment groups using the chi-square test for categorical variables and the t test for continuous variables. We calculated the standardized difference expressed in percentage points between 2 treatment groups as the difference in means or proportions divided by a pooled estimate of the SD. Standardized differences less than 10 percentage points suggest balance in the 2 groups with respect to that variable (21). We estimated the cumulative incidence of each outcome at 1 year and 3 years after device implantation for both treatment groups. Estimates of mortality were based on the KaplanMeier estimator, and differences between groups were assessed using log-rank tests. Estimates of readmission were based on the cumulative incidence function, which accounts for the competing risk for mortality. For patients not having an event, we defined a censoring date as the earliest among the end of follow-up at 1 year or 3 years after the index discharge date, the end of claims data availability on 31 December 2011, or the date on which the patient enrolled in a Medicare managed care plan. We used Gray tests to assess differences between treatment groups (22). We used propensity score matching to account for differenc