Author + information
- Received February 17, 2015
- Revision received April 1, 2015
- Accepted April 23, 2015
- Published online August 1, 2015.
- Peter A. Noseworthy, MD∗,†∗ (, )
- Holly K. Van Houten, BS†,
- Lindsey R. Sangaralingham, MPH†,
- Abhishek J. Deshmukh, MBBS∗,
- Suraj Kapa, MD∗,
- Siva K. Mulpuru, MD∗,
- Christopher J. McLeod, MBBS∗,
- Samuel J. Asirvatham, MD∗,
- Paul A. Friedman, MD∗,
- Nilay D. Shah, PhD†,‡ and
- Douglas L. Packer, MD∗
- ∗Heart Rhythm Section, Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- †Robert D. and Patricia E. Kern Center for Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota
- ‡Optum Labs, Cambridge, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Peter A. Noseworthy, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55902.
Objectives This study sought to evaluate the impact on antiarrhythmic drug (AAD) initiation on the risk of readmission after catheter ablation for atrial fibrillation (AF) among patients not already treated with an AAD.
Background Hospital readmission, a commonly tracked indicator of quality and efficiency of care delivery, occurs in about 15% patients within 90 days of undergoing catheter ablation for AF.
Methods Using a large national administrative claims database, we identified all atrial fibrillation patients (≥18 years of age) who underwent catheter ablation between January 2005 and December 2013 (n = 7,442). We identified the subset of patients who had not been on an AAD in the 90 days before ablation (n = 2,542) and, among those, the patients in whom an AAD was initiated at discharge following the ablation (n = 519).
Results The readmission rate was significantly lower among patients who were initiated on an AAD compared with those who were not (11.6% vs. 16.2%, p = 0.009). The association persisted after adjustment for age, sex, Charlson index, and CHADS2 score (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.56 to 0.97; p = 0.03). In unadjusted time to event analysis, amiodarone (HR: 0.55, 95% CI: 0.32 to 0.94; p = 0.039) was associated with the greatest reduction in readmission whereas dronedarone, Class II agents, and Class IC agents had no statistically significant effect on readmission. AADs were discontinued in 44.5% of patients at 3 months.
Conclusions Initiation of an AAD at discharge of catheter ablation is associated with a significant reduction in readmission within 90 days. Routine initiation of an AAD after catheter ablation may reduce healthcare utilization in the periablation period; however, the high rate of medication discontinuation may suggest that side effects or inefficacy may limit long-term AAD use post-ablation.
Early recurrence of arrhythmia is common immediately after atrial fibrillation (AF) ablation, and, although it is not always a harbinger of a failed ablation (1,2), data are mixed (3). Clinical trials of AF ablation commonly ignore the first 12 weeks after ablation, the so-called “blanking period” (4). Nevertheless, early AF recurrence and readmission is an important contributor to the morbidity and cost of the procedure—resulting in potentially unnecessary cardioversions, medication changes, and increasing the burden on patients and providers. Reducing readmission after ablation is an important goal of efficient and cost-effective AF management. Empiric antiarrhythmic drug (AAD) initiation during the blanking period may reduce early arrhythmia recurrence and readmission.
The prospective 5A (Antiarrhythmics after Ablation of Atrial Fibrillation) study randomized 110 patients with paroxysmal AF to either atrioventricular (AV) nodal blocking agents or AADs for 6 weeks after ablation. Patients on AADs were less likely to have AF recurrence requiring hospitalization (5). However, data are mixed and other studies have not demonstrated a benefit of empiric AAD use (6). Furthermore, the potential toxicities, incomplete efficacy, and costs of the AADs dissuade many providers from their empiric use. There is significant practice variation with respect to AAD use after ablation, which affords the opportunity to perform observational studies of the effect of this variation in practice on ablation outcomes.
We sought to use a large administrative database to assess the effect of AAD use post-ablation on the likelihood of readmission. Although retrospective and non-randomized, the strength of this approach is to provide a “real-world” assessment of outcomes after catheter ablation in clinical practice, outside the confines of a controlled clinical trial and with larger sample sizes than easily feasible in an interventional clinical trial.
We conducted a retrospective analysis of administrative claims data from the large database, Optum Labs Data Warehouse, which includes privately insured and a number of Medicare Advantage enrollees throughout the United States (7). This database includes individuals enrolled in private health plans as well as Medicare Advantage plans. The database contains data on over 100 million enrollees, from geographically diverse regions across the United States, with greatest representation in the South and Midwest U.S. census regions. The plan provides fully insured coverage for inpatient, outpatient, and pharmacy services. Medical claims include International Classification of Diseases-Ninth Revision-Clinical Modification (ICD-9-CM) diagnosis codes; ICD-9 procedure codes; Current Procedural Terminology, Version 4 procedure codes; Healthcare Common Procedure Coding System (HCPCS) procedure codes; site of service codes, and provider specialty codes (8). All study data is statistically deidentified according to the Health Insurance Portability and Accountability Act of 1996 (HIPAA) 164.514 Privacy Rule (9). All data are accessed using techniques compliant with HIPAA and, because this study involved analysis of pre-existing, deidentified data, it is exempt from Institutional Review Board approval.
We identified all AF patients (≥18 years of age) who had not been treated with an antiarrhythmic agent in the 90 days before undergoing catheter ablation between 2005 and 2013. Use of an AAD was defined as a prescription filled for any of the following medications: amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol, procainamide, disopyramide, or quinidine. We required patients to have continuous medical enrollment for at least 12 months before and 90 days after the index procedure. Patients were identified using ICD-9-CM and HCPCS—we searched physician and facility claims with a primary diagnosis of AF (ICD-9 427.31) during which a catheter ablation procedure (ICD-9 code 37.34 and/or HCPCS code 93651, 93656, 93657) was performed. We excluded patients with secondary diagnosis codes for Wolff-Parkinson-White syndrome (ICD-9 426.7), nonparoxysmal atrioventricular nodal tachycardia (ICD-9 426.89), paroxysmal supraventricular tachycardia (ICD-9 427.0), paroxysmal ventricular tachycardia (ICD-9 427.1), and ventricular premature beats (ICD-9 427.60, 427.61, 427.69). We also excluded patients with diagnostic or procedural codes indicating implantation of a pacemaker or implantable cardioverter-defibrillator before and during the index procedure to avoid inclusion of patients undergoing AV nodal ablation and pacemaker implantation for AF. Similar methodology has been used in existing literature to identify patients undergoing AF ablation from large administrative databases (10–13). Initiation of an AAD at discharge was defined as a prescription filled for any of the following medications on the day of or the day following discharge of the catheter ablation: amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol, procainamide, disopyramide, or quinidine.
We examined the demographic characteristics and prevalence of key comorbid conditions for patients who underwent catheter ablation. Demographic variables collected included the following: year of birth, sex, and race. Patients were grouped into 3 categories: 18 to 49 years of age, 50 to 64 years of age, and ≥65 years of age. For clinical characteristics, comorbid conditions were identified by ICD-9-CM codes in the primary or secondary diagnosis on any claim during the 12-month baseline period. The Charlson/Deyo comorbidity index (7) was used to assess the patient’s overall baseline comorbidity burden, using ICD-9-CM codes to identify the 17 conditions during the baseline period. CHADS2 score was calculated for each patient with a possible total score of 0 to 6 points and grouped into 3 categories: 0–1, 2, or 3+. The components of the CHADS2 score were also defined using diagnoses coded within the 12-month baseline period before the index procedure.
The main outcome measure was all-cause and AF- or atrial flutter-related time to readmission after the index procedure. We defined readmission as the first subsequent inpatient admission excluding transfers or admissions for inpatient rehabilitation. AF- and atrial flutter-related readmission was defined by a primary diagnosis of ICD-9 427.31 or 427.32. We required patients to be continuously enrolled from index date until 90 days post-discharge. In addition, we identified all emergency department admissions (that did not result in hospital admission) within 90 days post-discharge.
Data are presented as frequencies and means for all variables. We described baseline characteristics by antiarrhythmic initiation post-ablation. Patients were categorized into 2 groups on the basis of their periprocedural antiarrhythmic use. Univariate between-group comparisons were performed using chi-square tests for categorical and binary variables and Kruskal-Wallis tests for continuous variables. Associations between individual characteristics and time to readmission were estimated with Cox proportional hazards models. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were reported. Further, Cox proportional hazards modeling was used to assess the impact of antiarrhythmic medications on time to readmission, adjusted for those patient characteristics significant in univariate analysis (age, sex, Charlson index, and CHADS2 score). We used SAS software version 9.3 (SAS Institute Inc., Cary, North Carolina) for all analyses.
Between January 2005 and December 2013, 2,542 patients who had not been treated with an AAD in the 90-day run-in period underwent catheter ablation for AF (Table 1). Participants in our cohort were 59.8 ± 11.7 years of age, 70.3% were male, and 74.7% were white. The most common comorbidities were congestive heart failure (27.6%), diabetes including with organ damage (24.2%), and chronic pulmonary disease (20.8%). The mean CHADS2 score was 1.3 ± 1.1. A total of 387 (15.2%) ablation patients were readmitted within 90 days of ablation for any cause and 161 (6.3%) were readmitted with AF or atrial flutter as the primary discharge diagnosis.
In total, 519 patients filled a prescription for an AAD on the day of or the day following discharge after the ablation. The most common AADs used were amiodarone, sotalol, dronedarone, and flecainide (Table 2).
There was a significant reduction (p < 0.01) in the hospital readmission among those treated with an AAD (Figure 1). In the univariate models (Table 3), ≥65 years of age, females, Charlson index of ≥2 CHADS2 score of ≥2 were significantly associated with risk of readmission (p < 0.05). The association between AAD initiation and reduced readmission persisted after adjustment for age, sex, Charlson index, and CHADS2 score (HR: 0.73, 95% CI: 0.56 to 0.97; p = 0.03). AADs were discontinued in 1.9% of patients at 30 days, 25.2% at 60 days, and 44.5% at 90 days post-ablation.
The most common reason for readmission was cardiac dysrhythmia (Table 4). There was a significant reduction in readmission for AF/flutter from 7% with no AAD compared with 3.9% among those treated with an AAD (p = 0.01). In addition, though not significant, those treated with an AAD were less likely to suffer a complication of the procedure (0.58% compared with 1.4%; p = 0.14). Stratifying the cohort by first AAD prescribed, amiodarone (HR: 0.55, 95% CI: 0.32 to 0.94; p = 0.03) had a statistically significant effect on time to readmission, whereas the effect of Class IC agents, Class III agents, and dronedarone were nonsignificant (Table 5, Figure 2).
There was no significant difference between groups in the number of emergency department visits within 90 days of ablation (Table 6).
The major finding of this study is that, among patients not already on an AAD, initiation of an AAD at discharge following catheter ablation for AF is associated with a significant reduction in readmission. This finding persists after statistical adjustment for key comorbid conditions and patient variables. This “real-world” observation could have implications for optimizing periablation care and minimizing morbidity and healthcare utilization for patients undergoing catheter ablation for AF.
The immediate post-ablation period is particularly high risk for arrhythmia recurrence. Direct tissue injury from ablation can result in pericarditis and/or proarrhythmia involving depolarized, edematous, or inflamed tissue. While these arrhythmias are not typically thought to portent a poor prognosis, they are bothersome, discouraging, and can result in intense healthcare utilization (emergency department visits or hospitalization, cardioversions, medication adjustment, and outpatient visits). Regardless of the potential long-term implications of these early arrhythmias, minimizing them early after ablation could have a favorable impact on patient experience.
It is important to note that adherence to AAD therapy in our study was low. Indeed, nearly half of the patients had stopped taking the medication within the first 90 days post-ablation. With the available data, we cannot determine the reason for discontinuation, but side effects, cost, and patient preference may have played a role. Clearly, the potential benefit of empiric AAD use post-ablation needs to be weighed against the known toxicities and potential for proarrhythmia. Nonetheless, the observation that AAD therapy was associated with fewer readmissions despite the high rate of discontinuation, suggests that, at least in the short term, there may be a net benefit in terms of avoiding hospitalization.
There is currently only 1 major randomized trial that has examined the use of empiric AADs after ablation. The 5A study demonstrated that paroxysmal AF patients treated with AADs for 6 weeks after ablation were less likely to have AF recurrence than those treated with AV nodal blocking agents (5). This study was relatively small (n = 110) in comparison with our large observational experience but the results are consistent. They demonstrated about a 50% reduction in the rate of recurrent AF in the first weeks after ablation.
However, not all studies demonstrate a benefit of AAD post-ablation. A retrospective, nonrandomized, single-center study of 274 ablation patients demonstrated no difference in the rates of early AF recurrence among those treated with an AAD or an AV nodal blocking agent alone (6). Furthermore, 9 of the 185 patients treated with an AAD discontinued the medication due to side effects, suggesting a possibility for harm with an empiric AAD use strategy. However, unlike our study, most of these patients had been on an antiarrhythmic agent before the ablation (73% had been on flecainide, 47% on amiodarone, and 28% on dronedarone) so this was a study of AAD continuation/discontinuation rather than initiation. Furthermore, the AF recurrence rate in this study was 42% at 2 months, suggesting that this was a population with particularly recalcitrant AF. These data suggest that among patients with AAD-refractory AF, AAD continuation offers little benefit beyond the ablation itself.
It is important to emphasize that our study examined only outcomes in the 90 days after ablation. It is possible that AAD use simply delays arrhythmia recurrence and that it does not, as such, have a favorable long-term impact on outcomes. Indeed, 6-month follow up of the 5A study demonstrated that patients treated with AADs immediately after ablation had similar long-term rates of arrhythmia than those treated with AV nodal blocking agents alone (14). This indicates that early AAD use does not affect the underlying disease course, but simply suppresses nonspecific arrhythmias that do not necessarily indicate success or failure of the ablation in the long term. We do not believe that this indicates futility of post-ablation AAD use, but rather underscores its utility in minimizing avoidable proarrhythmia in the immediate post-ablation period.
The analyses stratified by AAD drug class demonstrate that amiodarone is superior to Class Ic or Class III agents in reducing early readmission. It is important to note that the samples size for these subgroup analyses is comparatively small and analyses may be underpowered. Nonetheless, these findings provide some evidence on the relative impact of various treatment options using natural practice variation.
Like all claims-based observational studies, there is the potential for undercoding or overcoding, which can reduce the accuracy of diagnoses and outcomes. We cannot infer the physician’s intent based solely on the prescribing pattern. For instance, it is impossible to know if a medication started the day of the ablation was empiric (started solely to try to reduce early recurrence) or was initiated due to an early recurrence. This limits our ability to make claims about potential practice changes that could be supported by these data. There are also outcomes that are hard to ascertain by claims analysis such as medication side effects, adverse reactions that may not meet the threshold to require a medical claim. There is also a possibility that AAD initiation would result in increased length of stay since some drugs require inpatient observation during initiation. This effect could offset some of the benefit of reduced rehospitalizations. In addition, we focused on the 90-day readmission rates as the follow-up outcome as this is a meaningful time frame to assess readmissions. However, this does not allow us to generate any inferences on long-term outcomes such as reablation, cardioversion, late readmission, or mortality.
Our study indicates that initiation of an AAD at discharge of catheter ablation is associated with reduced early rehospitalization. In particular, amiodarone appears to be most effective in this regard. Clinicians may consider empiric initiation of an AAD in order to reduce hospitalization in the immediate post-ablation period.
COMPETENCY IN MEDICAL KNOWLEDGE: Hospital readmission is a major driver of healthcare expenditure. Reducing readmission should be a goal of coordinated care for atrial fibrillation.
TRANSLATIONAL OUTLOOK: This study may inform antiarrhythmic medication treatment decisions at the time of hospital discharge to minimize risk of hospital readmission during the “blanking period” after catheter ablation for atrial fibrillation.
Dr. Packer has received research grant support for CABANA from Biosense, St. Jude, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- antiarrhythmic drug
- atrial fibrillation
- confidence interval
- hazard ratio
- International Classification of Diseases-9th Revision-Clinical Modification
- Received February 17, 2015.
- Revision received April 1, 2015.
- Accepted April 23, 2015.
- American College of Cardiology Foundation
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