Cardiology

Cost of Hospital Admission for Antiarrhythmic Drug Initiation in Atrial Fibrillation Michael H Kim, David Klingman, Jay Lin, Prathamesh Pathak, and David Battleman

he increasing prevalence of atrial fibrillation (AF) and atrial flutter and BACKGROUND: Initiation of some rhythm-control therapies for atrial fibrillation (AF) requires an inpatient hospital stay and telemetry monitoring, adding to the cost the associated costs of treatment represent burden of AF. However, specific cost data for inpatient initiation of AF therapies are a substantial burden to the US healthcare lacking. 1-3 system. The presence of AF is associatOBJECTIVE: To examine costs associated with initiating sotalol or dofetilide in the ed with a significant increase in the risk of inpatient setting in the US. adverse cardiovascular events and is an inMETHODS: This retrospective cohort study used data from billing/discharge dependent predictor of stroke and congesrecords in the Premier Perspective Database for adults with a primary diagnosis tive heart failure.4-8 Moreover, patients’ of AF, hospitalized between January 2002 and September 2007. Patients had to quality of life is greatly reduced as a rehave received 4 or more sotalol doses or 5 or more dofetilide doses starting within 2 days of admission (with ≥1 dose within 3 days of discharge). Patients sult of symptoms such as dizziness, pal9 admitted solely for AF drug initiation were identified by excluding patients who pitations, and reduced exercise capacity. were admitted on an emergency basis, received care in the emergency In total, the costs of management of AF department, or underwent major surgical procedures. The primary outcome was were estimated at approximately $6.65 direct medical costs for in-hospital services during the stay. billion in direct costs across hospitals, RESULTS: Among 7290 patients included in the analysis (4847 sotalol, 2443 payers, and patients in 2006.1 dofetilide), mean total inpatient costs per patient were $3278 in the sotalol group The use of antiarrhythmic drugs has and $3610 in the dofetilide group. The greatest costs were for room/board ($1874 sotalol, $1985 dofetilide) and cardiology/electrocardiograms ($394 been shown to be effective for the treatsotalol, $443 dofetilide). Pharmacy costs were $230 and $201 per patient in the ment of AF and atrial flutter and leads to sotalol and dofetilide groups, respectively. 9-12 an increase in patients’ quality of life. CONCLUSIONS: The admission of patients for in-hospital initiation of AF rhythmHowever, due to a risk of proarrhythmia control therapy represents a high cost burden in the US. with some rhythm-control therapies, parKEY WORDS: atrial fibrillation, dofetilide, drug initiation, sotalol. ticularly within the first 2–3 days of Ann Pharmacother 2009;43:840-8. starting treatment, initiating antiarrhythPublished Online, 5 May 2009, www.theannals.com, DOI 10.1345/aph.1L698 mic drugs often requires an inpatient hospital stay with telemetry or other electrocardiogram (ECG) monitoring for try to monitor the QT interval and assess for ventricular arrhythmic events. In particular, treatment guidelines recproarrhythmia.11,13-16 In the case of dofetilide, physicians ommend in-hospital initiation of the class III antiarrhythprescribing this drug must also have undertaken specialist mic sotalol, especially for patients with comorbid heart training in treatment initiation and dosing and received cerdisease, while the initiation of the class III agent dofetilide tification.13,14 These requirements are likely to add signifiis required by the Food and Drug Administration to be cantly to the cost burden of managing patients with AF. conducted on an inpatient basis for all AF patients, with a While the cost-effectiveness of initiating antiarrhythmic recommended minimum hospital stay of 3 days on telemedrugs for the treatment of supraventricular tachycardias inhospital has been demonstrated previously in clinical Author information provided at the end of the text. trials,17 to our knowledge, no studies have assessed the

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real-world cost burden of inpatient initiation of rhythmcontrol therapies for AF as the sole reason for admission in the US. To inform clinical planning and decision-making in relation to AF management, it is important to understand the overall costs of current treatment strategies and the potential benefits of therapies that do not require inpatient initiation. We therefore undertook a comprehensive analysis to examine healthcare utilization and the costs associated with initiating sotalol or dofetilide in the inpatient setting. Methods STUDY DESIGN

This retrospective cohort study used data from inpatient billing/discharge records in the Premier Perspective Database between January 1, 2002, and September 30, 2007. This database contains detailed clinical and financial data from 200 not-for-profit hospitals and healthcare systems, including large systems operating multiple hospitals, academic medical centers associated with universities, and community-owned hospitals. Annually, more than 5 million hospital discharges are processed and recorded in the Premier database. Data from this database have been used previously for a broad range of health outcomes and health economics studies.18-21 Information from this database is also used for postmarketing drug surveillance supporting the Office of Surveillance and Epidemiology and the Office of New Drugs, Pediatric and Maternal Health of the US Food and Drug Administration. The database complied with all aspects of the Health Information Portability and Accountability Act of 1996, and all patient data were deidentified. PATIENTS

The database was screened to identify adults (aged ≥18 y) hospitalized with a primary diagnosis of AF (ICD -9CM diagnosis code 427.31) or atrial flutter (ICD -9-CM diagnosis code 427.32) during the study period. To be included in the study population, patients had to have received 4 or more sotalol doses (80–240 mg) or 5 or more dofetilide doses (125–500 µg), starting within 2 days of hospital admission and with at least 1 dose administered 3 days or fewer prior to discharge. Although the product labels for both sotalol and dofetilide recommend 3 or more days of inpatient monitoring with dosing every 12 hours (6 doses in total),14,15 in some practices, sotalol is initiated in the outpatient setting. In addition, practice variability in inpatient initiation ranges from 4 to 6 doses, which we wanted to capture in the analysis. Only the first eligible stay for each patient was selected. Patients admitted solely for AF drug initiation were identified by excluding those who were admitted on an emerwww.theannals.com

gency basis, received care in the emergency department, or underwent major surgical procedures during the stay (Figure 1). OUTCOME MEASURES

The primary outcome measure was direct medical costs for in-hospital services during the stay, including AF-related procedures, room and board, professional fees for services performed by hospital staff (excluding attending physicians’ fees, which are charged separately and are therefore not captured in the Premier database), and pharmacy costs. All cost figures were inflation-adjusted to 2007 prices using the Medical Care component of the US Consumer Price Index for All Urban Consumers.22 STATISTICAL ANALYSES

All analyses were conducted using SAS version 9 (SAS Institute Inc., Cary, NC). The mean, standard deviation, and median costs for each type of in-hospital service, as well as total costs, were summarized and reported for the total study population and by therapy group (sotalol or dofetilide). Given the descriptive nature of the study, no formal tests of the statistical significance of differences between the 2 therapy groups were performed. Severity of illness was estimated using the All Patient Refined-Diagnosis Related Groups severity level.23,24 Results PATIENT CHARACTERISTICS

Overall, 260,084 patients in the database had a primary diagnosis of AF or atrial flutter, and 28,951 had received either 4 or more doses of sotalol or 5 or more doses of dofetilide during their inpatient stay (beginning by the second day of the stay). Of these, 7290 patients met the study inclusion criteria for hospitalization for the initiation of sotalol (n = 4847) or dofetilide (n = 2443) (Figure 1). Patient characteristics were similar in both treatment groups (Table 1). Overall, the mean age was 66 years and 59% of patients were male. The most common comorbidities were hypertension (53%), hyperlipidemia (30%), and coronary atherosclerosis (18%) (Table 1). HEALTHCARE SERVICES UTILIZATION

The majority (93%) of patients were admitted to the hospital for 4 days or less, with a median stay of 2 days in the sotalol group and 3 days in the dofetilide group (mean length of stay 3 days in both groups). For most (89%) patients, the attending physician was a cardiologist (Table 2). The majority (85%) of patients had 2 or more ECGs performed during their hospital stay, with a median of 3 in the

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sotalol group and 4 in the dofetilide group. This is broadly in-line with requirements for monitoring the QT-interval response to dofetilide and, ideally, also to sotalol.11,14,15 Both drugs can prolong the QT interval, predisposing patients to a higher risk of ventricular proarrhythmia. This is the principal reason for in-hospital initiation of both agents. Overall, 34% of patients underwent electrical cardioversion (Table 3), which is often performed after administration of an antiarrhythmic drug if AF persists. In these patients, electrical cardioversion is used to restore normal sinus rhythm and the antiarrhythmic drug is used to maintain sinus rhythm. Approximately 12% of patients underwent transesophageal ECG (Table 3), which is performed to exclude left atrial clot and reduce the risk of stroke with con-

version of AF to sinus rhythm in patients without adequate anticoagulation. Adequate anticoagulation would be required whether an antiarrhythmic drug is used for chemical cardioversion or for electrical cardioversion. Accordingly, most (85%) patients received anticoagulant therapy with warfarin during their hospital stay and 35% received aspirin. To monitor anticoagulation, most (91%) patients had a prothrombin time test and 42% had a partial thromboplastin time test (Table 3). HEALTHCARE SERVICES COSTS

The mean total AF-related inpatient costs per patient were $3389 overall: $3278 in the sotalol group and $3610 in the dofetilide group (Table 4). The greatest costs in both

Figure 1. Patient disposition. AF = atrial fibrillation.

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Cost of Antiarrhythmic Drug Initiation

groups were for room and board ($1874 with sotalol, $1985 dofetilide), which accounted for 56% of total costs across both groups, followed by cardiology/ECGs ($394 with sotalol, $443 with dofetilide), which accounted for 12% of total costs. Pharmacy costs were $230 and $201 per patient in the sotalol and dofetilide groups, respectively (Table 4; 6% of total costs). Discussion This retrospective cohort study demonstrates that inhospital initiation of the antiarrhythmic therapies sotalol and dofetilide represents a large cost burden in the US, costing around $3389 per patient for the hospital stay during which therapy is initiated. As expected, the highest

proportion of overall costs was accounted for by expenses for room and board (56%), followed by cardiology/ECGs (12%). In addition, over a third of all patients underwent electrical cardioversion, adding further to the costs of AF treatment in these patients. The pattern of expenditure was similar for both sotalol and dofetilide. A recent study by Coyne et al.1 estimated the total cost burden of AF in the US to be $6.65 billion in 2006, with almost three-quarters of costs attributed to inpatient expenses. Similar to our study, in which pharmacy costs accounted for only approximately 6% of total costs, Coyne et al. estimated that only 4% of total expenditure was related to drug costs. Other analyses have estimated annual costs of AF at approximately $4700 per patient,25 or around €1500–3000 in European studies (approximately $2024–

Table 1. Patient Characteristics and Comorbidities Characteristic

Total (N = 7290)

Sotalol (n = 4847)

Dofetilide (n = 2443)

Male, n (%)

4288 (58.8)

2725 (56.2)

1563 (64.0)

Age (y), mean ± SD

66.2 ± 11.7

66.8 ± 11.7

65.1 ± 11.6

75

1718 (23.6)

1229 (25.4)

489 (20.0) 2007 (82.2)

Age (y), n (%)

Race/ethnicity, n (%) white

5975 (82.0)

3968 (81.9)

African American

183 (2.5)

134 (2.8)

49 (2.0)

Hispanic

165 (2.3)

126 (2.6)

39 (1.6)

other

967 (13.3)

619 (12.8)

348 (14.2)

Medicare

4161 (57.1)

2852 (58.8)

1309 (53.6)

Medicaid

101 (1.4)

63 (1.3)

38 (1.6)

2774 (38.1)

1742 (35.9)

1032 (42.2)

Source of payment, n (%)

private or commercial

58 (0.8)

52 (1.1)

6 (0.3)

196 (2.7)

138 (2.8)

58 (2.4)

1586 (21.8)

1004 (20.7)

582 (23.8)

872 (12.0)

579 (12.0)

293 (12.0)

South

3910 (53.6)

2752 (56.8)

1158 (47.4)

West

922 (12.7)

512 (10.6)

410 (16.8)

no insurance other/unknown Geographic region, n (%) Midwest Northeast

Comorbidities, n (%) hypertension

3824 (52.5)

2628 (54.2)

1196 (49.0)

hyperlipidemia

2195 (30.1)

1415 (29.2)

780 (31.9)

coronary atherosclerosis

1282 (17.6)

889 (18.3)

393 (16.1)

diabetes mellitus

1084 (14.9)

774 (16.0)

310 (12.7)

832 (11.4)

486 (10.0)

346 (14.2)

heart failure Severity of illness,23,24,a n (%) minor

3545 (48.6)

2398 (49.5)

1147 (47.0)

moderate

3141 (43.1)

2090 (43.1)

1051 (43.0)

594 (8.2)

352 (7.3)

242 (9.9)

10 (0.1)

7 (0.1)

3 (0.1)

major risk of mortality a

All Patient Refined-Diagnosis Related Groups.

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4048 based on exchange rates at time of writing),26 and consistently suggest that AF-related hospitalization costs represent the highest economic burden.1,25-31 In our study, the total costs relating to hospital stays in patients admitted for the initiation of sotalol or dofetilide were approximately $3389 per patient. Compared with

overall per patient costs from previous studies, the costs of in-hospital therapy initiation are likely to represent a substantial contribution to overall healthcare expenditure for AF in the US. Assuming that an estimated 116,538 patients with AF currently receive sotalol or dofetilide (based on a US prevalence of 2.44 million with AF2 and given

Table 2. Hospital and Clinical Characteristics Total (N = 7290)

Sotalol (n = 4847)

2

3069 (42.1)

2496 (51.5)

573 (23.5)

3–4

3722 (51.1)

2009 (41.5)

1713 (70.1)

5–6

371 (5.1)

249 (5.1)

122 (5.0)

≥7

128 (1.8)

93 (1.9)

35 (1.4)

2.9 ± 1.3 (3)

2.8 ± 1.4 (2)

3.1 ± 1.0 (3)

urban

6725 (92.2)

4368 (90.1)

2357 (96.5)

rural

565 (7.8)

479 (9.9)

86 (3.5)

teaching

3828 (52.5)

2339 (48.3)

1489 (61.0)

nonteaching

3462 (47.5)

2508 (51.7)

954 (39.1)

1–500 beds

4226 (58.0)

3150 (65.0)

1076 (44.0)

>500 beds

3064 (42.0)

1697 (35.0)

1367 (56.0) 2327 (95.3)

Characteristic

Dofetilide (n = 2443)

Length of stay, days, n (%)

mean ± SD (median) Hospital type, n (%)

Attending physician specialty, n (%) cardiology

6452 (88.5)

4125 (85.1)

internal medicine

509 (7.0)

437 (9.0)

72 (3.0)

other

329 (4.5)

285 (5.9)

44 (1.8)

Table 3. Atrial Fibrillation–Related Procedures Total (N = 7290)

Sotalol (n = 4847)

Dofetilide (n = 2443)

2462 (33.8)

1775 (36.6)

687 (28.1)

849 (11.7)

595 (12.3)

254 (10.4)

1537 (21.1)

1133 (23.4)

404 (16.5)

0

398 (5.5)

313 (6.5)

85 (3.5)

1

705 (9.7)

645 (13.3)

60 (2.5)

2–3

3534 (48.5)

2649 (54.7)

885 (36.2)

≥4

2653 (36.4)

1240 (25.6)

1413 (57.8)

mean ± SD (median)

3.0 ± 1.4 (3)

2.7 ± 1.3 (3)

3.6 ± 1.3 (4)

Procedure Electrical cardioversion, n (%) Transesophageal echocardiogram, n (%) Other type echocardiogram, n (%) Electrocardiograms, n (%)

Prothrombin time tests, n (%) 0

694 (9.5)

431 (8.9)

263 (10.8)

1

1495 (20.5)

1021 (21.1)

474 (19.4)

2–3

3091 (42.4)

2206 (45.5)

885 (36.2)

≥4

2010 (27.6)

1189 (24.5)

821 (33.6)

mean ± SD (median)

2.6 ± 1.6 (3)

2.5 ± 1.6 (3)

2.6 ± 1.7 (3)

0

4254 (58.4)

2719 (56.1)

1535 (62.8)

1

2226 (30.5)

1553 (32.0)

673 (27.6)

2–3

514 (7.1)

344 (7.1)

170 (7.0)

≥4

296 (4.1)

231 (4.8)

65 (2.7)

0.7 ± 1.2 (0)

0.7 ± 1.2 (0)

0.6 ± 1.0 (0)

Partial thromboplastin time tests, n (%)

mean ± SD (median)

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Table 4. Mean Atrial Fibrillation–Related Hospital Services Costs per Patient Servicea Room and board pts. using service, n (%) cost ($), mean ± SD percentage of total costs Cardiology/electrocardiogram pts. using service, n (%) cost ($), mean ± SD percentage of total costs Pharmacyb pts. using service, n (%) cost ($), mean ± SD percentage of total costs Laboratory pts. using service, n (%) cost ($), mean ± SD percentage of total costs Supplyc pts. using service, n (%) cost ($), mean ± SD percentage of total costs Radiology pts. using service, n (%) cost ($), mean ± SD percentage of total costs Operating room pts. using service, n (%) cost ($), mean ± SD percentage of total costs Respiratory pts. using service, n (%) cost ($), mean ± SD percentage of total costs Professional feesd pts. using service, n (%) cost ($), mean ± SD percentage of total costs Therapye pts. using service, n (%) cost ($), mean ± SD percentage of total costs Otherf pts. using service, n (%) cost ($), mean ± SD percentage of total costs Unknown pts. using service, n (%) cost ($), mean ± SD percentage of total costs Total costs ($), mean ± SD a

Total (N = 7290)

Sotalol (n = 4847)

Dofetilide (n = 2443)

7288 (100.0) 1911 ± 1473 56.4

4845 (100.0) 1874 ± 1422 57.2

2443 (100.0) 1985 ± 1568 55.0

7101 (100.0) 411 ± 1961 12.1

4707 (100.0) 394 ± 2359 12.0

2394 (100.0) 443 ± 658 12.3

7290 (100.0) 220 ± 425 6.5

4847 (100.0) 230 ± 492 7.0

2443 (100.0) 201 ± 244 5.6

7226 (99.1) 183 ± 195 5.4

4795 (98.9) 192 ± 212 5.9

2431 (99.5) 166 ± 153 4.6

5319 (73.0) 153 ± 1592 4.5

3479 (71.8) 144 ± 1324 4.4

1840 (75.3) 171 ± 2022 4.7

2410 (33.1) 76 ± 235 2.2

1894 (39.1) 90 ± 248 2.7

516 (21.1) 47 ± 203 1.3

1711 (23.5) 67 ± 276 2.0

1253 (25.9) 73 ± 280 2.2

458 (18.7) 54 ± 269 1.5

1355 (18.6) 21 ± 211 0.6

977 (20.2) 22 ± 251 0.7

378 (15.5) 19 ± 84 0.5

1483 (20.3) 12 ± 53 0.4

1036 (21.4) 12 ± 58 0.4

447 (18.3) 12 ± 42 0.3

165 (2.3) 5 ± 55 0.1

130 (2.7) 7 ± 64 0.2

35 (1.4) 2 ± 27 0.1

4767 (65.4) 330 ± 842 9.7

3062 (63.2) 239 ± 591 7.3

1705 (69.8) 511 ± 1172 14.2

3 (0) 0±6 0 3389 ± 3376

3 (0.1) 0±8 0 3278 ± 3505

0 (0) 0 0 3610 ± 3094

Categories are departmental line-item charges as recorded in the Premier Perspective database. Mean costs were calculated across the total population. b Includes all pharmaceutical treatments. c Includes general medical supplies (eg, cannulas, shunts, suture needles). d Includes professional fees for services performed by hospital staff, such as surgical procedures and diagnostic tests (excludes attending physicians’ fees, which are charged separately and are therefore not captured in the Premier Perspective database). e Includes physical medicine and physical, occupational, and speech therapy. f Includes durable medical equipment, nursing labor, ambulance, and facility fees for diagnostic and therapeutic services not classified elsewhere.

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that sotalol/dofetilide are prescribed in approximately 5% of AF patients [unpublished data]), we estimate that the per patient costs in this study translate to a total cost burden in the US of at least $395 million. This is a conservative estimate, as many patients are likely to need to reinitiate therapy over the course of their treatment due to drug titration or as a result of missing doses, and thus incur additional costs. The proportion of patients who discontinue sotalol (measured by a gap in therapy of ≥60 days) has been demonstrated to be approximately 40% over 1 year,32,33 suggesting that a relatively high proportion of patients would need to be admitted to reinitiate therapy following a gap in treatment. Where clinically indicated, alternative antiarrhythmics that are typically initiated in the outpatient setting, such as amiodarone, could reduce the overall cost of treatment by negating the costs associated with in-hospital initiation. However, even for antiarrhythmics initiated in the outpatient setting, close monitoring of patients is recommended, and this is likely to be associated with additional healthcare costs.34 An alternative to drug therapy is radiofrequency catheter ablation to restore sinus rhythm. Although the procedure is costly (around $8607), a recent study has suggested that this would be cost-neutral after 2 years when compared with drug treatment.35 However, AF catheter ablation is associated with potential complications and is usually recommended for use only in patients with highly symptomatic AF who have failed to respond to at least one antiarrhythmic drug.11 A potential limitation of this study is that it was not possible to guarantee that the patients included in our analysis were solely admitted for antiarrhythmic therapy initiation, particularly as information on patients’ prior history was not available. However, the inclusion/exclusion criteria applied were designed specifically to select patients admitted primarily for drug initiation as far as was possible. Furthermore, the average length of hospital stay of 3 days was broadly consistent with recommendations for antiarrhythmic drug initiation, and the frequency of ECGs was as might be expected for telemetry monitoring, confirming that therapy initiation was likely to be the primary reason for admission in the majority of cases. In addition, we are not able to draw firm conclusions on whether costs incurred during a patient’s hospi-

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tal stay would have been avoided if antiarrhythmic therapy had been initiated in the outpatient setting. However, more than two-thirds of all costs were accounted for by room and board (~56%) and cardiology/ECGs (~12%), which were likely to have been related specifically to the hospital stay for drug initiation. Nonetheless, we can only speculate on the precise reasons for healthcare resource utilization in these patients. Additional limitations of this study include its retrospective, nonrandomized design and the fact that the database does not capture a patient’s activity outside of the Premier group of hospitals. Costs charged outside of the hospital billing system, including attending physicians’ fees, are also not recorded in the database; thus, the overall costs of inpatient initiation of therapy are likely to be higher than estimated in this analysis. Furthermore, practice patterns in not-for-profit hospitals and healthcare systems included in the database may not be representative of those in all US hospitals, and their patients may not be representative of all US hospital patients. Compared with previous studies among patients with AF or atrial flutter,2,3,36 patients included in our analysis had a lower incidence of heart failure and a relatively low overall severity of illness; however, this was as expected given the selection criteria applied, which excluded patients undergoing major surgical procedures or who were admitted on an emergency basis. While the cost-effectiveness of in-hospital initiation of antiarrhythmic drugs compared with outpatient treatment has been demonstrated in a meta-analysis of 57 clinical trials,17 we believe that our study is the first to examine the overall costs of admitting patients for the initiation of therapies such as sotalol and dofetilide in the real-world clinical practice setting. These data provide valuable information to help healthcare providers to determine the most appropriate strategies for AF management. Future studies would also be worthwhile to investigate the real-world incidence and costs associated with adverse drug events associated with antiarrhythmic therapy initiation to fully evaluate the costeffectiveness of available treatment strategies. In addition, our results highlight the need for novel AF therapies that can be safely and effectively initiated in the outpatient setting. Such therapies would have the potential to both dramatically improve patients’ quality of life and reduce the overall cost of managing this condition. Hospital admission of patients for initiation of AF rhythm-control therapies represents a high cost burden in the US, which should be considered when determining the most appropriate treatment strategies for AF patients. Michael H Kim MD, Associate Professor, Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, IL David Klingman PhD, Senior Director, Health Economics and Outcomes Research, IMS Health, Inc., Falls Church, VA Jay Lin PhD MBA, Director, CV Health Outcomes, sanofi-aventis, Bridgewater, NJ

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Prathamesh Pathak BPharm MS, Consultant, Health Economics and Outcomes Research, IMS Health, Inc.

David S Battleman MD MSc MBA, Principal, Health Economics and Outcomes Research, IMS Health, Inc.

Reprints: Dr. Kim, Feinberg School of Medicine, Northwestern University, 251 E. Huron St., Feinberg Pavilion, Suite 8-542, Chicago, IL 60611, fax 312/926-0607, [email protected] Dr. Kim is a research consultant to sanofi-aventis. Drs. Klingman, Pathak, and Battleman are employees of IMS Health, which has a research consulting agreement with sanofi-aventis. Financial and editorial support for this article have been provided by sanofi-aventis US, Inc. Editorial support was provided by Elizabeth Harvey PhD.

References 1. Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M, Zimetbaum P. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health 2006;9:348-56. DOI 10.1111/j.1524-4733.2006.00124.x 2. Go AS, Hylek EM, Phillips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-5. 3. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114: 119-25. Epub 3 Jul 2006. DOI 10.1161/CIRCULATIONAHA.105.595140 4. Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: populationbased estimates. Am J Cardiol 1998;82:2N-9. 5. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994;154:1449-57. 6. Estes NA 3rd, Halperin JL, Calkins H, et al. ACC/AHA/Physician Consortium 2008 Clinical Performance Measures for Adults with Nonvalvular Atrial Fibrillation or Atrial Flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation) Developed in Collaboration with the Heart Rhythm Society. J Am Coll Cardiol 2008;51:865-84. DOI 10.1016/j.jacc.2008.01.006 7. Fang MC, Go AS, Chang Y, Borowsky L, Pomernacki NK, Singer DE. Comparison of risk stratification schemes to predict thromboembolism in people with nonvalvular atrial fibrillation. J Am Coll Cardiol 2008; 51:810-5. DOI 10.1016/j.jacc.2007.09.065 8. Krahn AD, Manfreda J, Tate RB, Mathewson FA, Cuddy TE. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. Am J Med 1995;98:476-84. DOI 10.1016/S0002-9343(99)80348-9 9. Thrall G, Lane D, Carroll D, Lip GY. Quality of life in patients with atrial fibrillation: a systematic review. Am J Med 2006;119:448 e1- 448e19. DOI 10.1016/j.amjmed.2005.10.057 10. Norgaard BL, Wachtell K, Christensen PD, et al. Efficacy and safety of intravenously administered dofetilide in acute termination of atrial fibrillation and flutter: a multicenter, randomized, double-blind, placebo-controlled trial. Danish Dofetilide in Atrial Fibrillation and Flutter Study Group. Am Heart J 1999;137:1062-9. 11. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006;114:e257-354. DOI 10.1161/CIRCULATIONAHA.106.177292

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Cost of Antiarrhythmic Drug Initiation 12. Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352:1861-72. DOI 10.1056/NEJMoa041705 13. Tran A, Vichiendilokkul A, Racine E, Milad A. Practical approach to the use and monitoring of dofetilide therapy. Am J Health Syst Pharm 2001; 58:2050-9. 14. Product information. Tikosyn (dofetilide). New York: Pfizer Inc., revised November 1999. 15. Product information. Betapace (sotalol hydrochloride). Montville, NJ: Bayer HealthCare Pharmaceuticals Inc., revised April 2007. 16. Makaryus AN, Hametz CD, Cohen TJ, Jadonath RL. Should the initiation of antiarrhythmic therapy for atrial fibrillation occur in the hospital or out of the hospital? A review of the literature. J Invasive Cardiol 2004; 16:31-4. 17. Simons GR, Eisenstein EL, Shaw LJ, Mark DB, Pritchett EL. Cost effectiveness of inpatient initiation of antiarrhythmic therapy for supraventricular tachycardias. Am J Cardiol 1997;80:1551-7. 18. Ouriel K, Kaul AF, Leonard MC. Clinical and economic outcomes in thrombolytic treatment of peripheral arterial occlusive disease and deep venous thrombosis. J Vasc Surg 2004;40:971-7. DOI 10.1016/j.jvs.2004.08.023 19. Blanchette CM, Wang PF, Joshi AV, Kruse P, Asmussen M, Saunders W. Resource utilization and costs of blood management services associated with knee and hip surgeries in US hospitals. Adv Ther 2006;23:54-67. 20. Delaney CP, Chang E, Senagore AJ, Broder M. Clinical outcomes and resource utilization associated with laparoscopic and open colectomy using a large national database. Ann Surg 2008;247:819-24. DOI 10.1097/SLA.0b013e31816d950e 21. Vekeman F, McKenzie RS, Lefebvre P, et al. Dose and cost comparison of erythropoietic agents in the inpatient hospital setting. Am J Health Syst Pharm 2007;64:1943-9. DOI 10.2146/ajhp060585 22. US Department of Labor. Consumer Price Index. http://data.bls.gov/cgi-bin/ surveymost?cu (accessed 2008 Nov 16). 23. 3M Health Information Systems. All Patient Refined Diagnosis Related Groups (APR-DRGs): methodology overview. Wallingford, CT: 3M Health Information Systems, 1998. 24. HSS, Inc. Definitions manual for All-Payer Severity-adjusted DRG (APS-DRGs) Assignment. Germantown, MD: HSS, Inc., 2003. 25. Reynolds MR, Essebag V, Zimetbaum P, Cohen DJ. Healthcare resource utilization and costs associated with recurrent episodes of atrial fibrillation: the FRACTAL registry. J Cardiovasc Electrophysiol 2007;18:62833. Epub 19 Apr 2007. DOI 10.1111/j.1540-8167.2007.00819.x 26. Ringborg A, Nieuwlaat R, Lindgren P, et al. Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation. Europace 2008;10:403-11. Epub 7 Mar 2008. DOI 10.1093/europace/eun048 27. Wu EQ, Birnbaum HG, Mareva M, et al. Economic burden and co-morbidities of atrial fibrillation in a privately insured population. Curr Med Res Opin 2005;21:1693-9. DOI 10.1185/030079905X65475 28. Kozak LJ, Lees KA, DeFrances CJ. National Hospital Discharge Survey: 2003 annual summary with detailed diagnosis and procedure data. Vital Health Stat 13 2006;(160):1-206. 29. Le Heuzey JY, Paziaud O, Piot O, et al. Cost of care distribution in atrial fibrillation patients: the COCAF study. Am Heart J 2004;147:121-6. 30. McBride D, Mattenklotz AM, Willich SN, Brüggenjürgen B. The costs of care in atrial fibrillation and the effect of treatment modalities in Germany. Value Health 2008;12:293-301. Epub 24 Jul 2008. DOI 10.1111/j.1524-4733.2008.00416.x 31. Wolf PA, Mitchell JB, Baker CS, Kannel WB, D’Agostino RB. Impact of atrial fibrillation on mortality, stroke, and medical costs. Arch Intern Med 1998;158:229-34. 32. Ishak JK, Proskorovsky I, Guo S et al. Persistence with amiodarone or sotalol and its impact on recurrence of atrial fibrillation. Presented at: International Society for Pharmacoeconomics and Outcomes Research 11th Annual European Congress, Athens, Greece, November 8–11, 2008. 33. Zimetbaum P, Ho KK, Olshansky B, et al. Variation in the utilization of antiarrhythmic drugs in patients with new-onset atrial fibrillation. Am J Cardiol 2003;91:81-3.

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34. Bickford CL, Spencer AP. Adherence to the NASPE guideline for amiodarone monitoring at a medical university. J Manag Care Pharm 2006; 12:254-9. 35. Khaykin Y, Wang X, Natale A, et al. Cost comparison of ablation versus antiarrhythmic drugs as first-line therapy for atrial fibrillation: an economic evaluation of the RAAFT pilot study. J Cardiovasc Electrophysiol 2009;20:7-12. 36. Granada J, Uribe W, Chyou PH, et al. Incidence and predictors of atrial flutter in the general population. J Am Coll Cardiol 2000;36:2242-6.

Costo de Admisión Hospitalaria para Iniciar Medicamento Antiarrítmico en Fibrilación Atrial MH Kim, D Klingman, J Lin, P Pathak, y D Battleman Ann Pharmacother 2009;43:840-8. EXTRACTO

El inicio de algunas terapias de control de ritmo cardíaco para fibrilación atrial requiere hospitalización y monitoreo con telemetría, lo que abona al peso del costo de la fibrilación atrial. Sin embargo, se carece de datos específicos sobre costo del inicio de terapias de fibrilación atrial a nivel ambulatorio. OBJETIVO: Examinar los costos asociados con inicio de sotalol o dofetilida en el escenario ambulatorio en los Estados Unidos. MÉTODOS: Este estudio de cohorte retrospectivo usó datos de récords de facturación/alta de la base de datos Premier Perspective para adultos con un diagnóstico primario de fibrilación atrial, hospitalizados entre enero 2002–septiembre 2007. Los pacientes tenían que haber recibido ≥4 dosis de sotalol ó ≥5 dosis de dofetilida comenzando dentro de los 2 días de la admisión (con ≥1 dosis dentro de los 3 días del alta). Los pacientes admitidos solamente para inicio de farmacoterapia para fibrilación atrial fueron identificados mediante exclusión de pacientes que fueron admitidos por emergencia, que recibieron cuidado en el departamento de emergencia, o que sufrieron procedimientos quirúrgicos mayores. El resultado primario fue costos médicos directos por servicios hospitalarios durante la estadía. RESULTADOS: Entre los 7290 pacientes incluidos en el análisis (4847 sotalol, 2443 dofetilida) el costo total promedio de hospitalización por paciente fue $3278 en el grupo de sotalol y $3610 en el grupo de dofetilida. Los costos mayores fueron por habitación ($1874 sotalol, $1985 dofetilida) y cardiología/electrocardiogramas ($394 sotalol, $443 dofetilida). Los costos de farmacia fueron $230 y $201 por paciente en los grupos de sotalol y dofetilida, respectivamente. CONCLUSIONES: La admisión de pacientes para inicio de terapia de control de ritmo cardíaco en fibrilación atrial representa un peso de alto costo en los Estados Unidos. TRASFONDO:

Traducido por Ana E Vélez

Coûts des Admissions Hospitalières lors de l’Initiation d’Antiarythmiques dans la Fibrillation Auriculaire MH Kim, D Klingman, J Lin, P Pathak, et D Battleman Ann Pharmacother 2009;43:840-8. RÉSUMÉ INTRODUCTION: L’initiation d’une thérapie de contrôle du rythme lors de fibrillation auriculaire (FA) requiert un séjour hospitalier et un suivi télémétrique, ajoutant aux coûts de traitement. Cependant, les données monétaires associées à une telle hospitalisation sont inexistantes. OBJECTIF: Examiner les coûts associés à l’initiation du sotalol ou du dofétilide auprès de patients hospitalisés aux États-Unis. MÉTHODOLOGIE: Cette étude rétrospective de cohorte a utilisé des données de facturation/départ de l’hôpital d’une base de données (Premier Perspective) pour des adultes souffrant de FA et hospitalisés entre janvier

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2002 et septembre 2007. Les patients devaient avoir reçu ≥4 doses de sotalol ou ≥5 doses de dofétilide et avoir débuté ces médicaments dans les 2 jours suivant l’admission (avec ≥1 dose en dedans de 3 jours du départ de l’hôpital). Les patients admis exclusivement pour l’initiation d’anti-arythmique furent identifiés en excluant ceux admis sur une base urgente, ceux ayant reçu des soins à l’urgence et ceux ayant subi des procédures chirurgicales majeures. Le résultat primaire recherché était les coûts médicaux directs pour les services hospitaliers reçus. RÉSULTATS: Parmi les 7290 patients inclus dans l’analyse (4847 avec le sotalol et 2443 avec le dofétilide), les coûts moyens d’hospitalisation par patient furent de $3278 dans le groupe sotalol et de $3610 dans le groupe dofétilide. Les coûts les plus importants furent attribués à ceux provenant

du logement ($1874 dans le groupe sotalol et $1985 dans le groupe dofétilide) et ceux provenant du service de cardiologie et des électrocardiographes ($394 dans le groupe sotalol et $443 dans le groupe dofétilide). Les coûts de pharmacie furent de $230 et de $201 par patient dans les groupes sotalol et dofétilide, respectivement. CONCLUSIONS: L’admission des patients à l’hôpital pour l’initiation d’une thérapie de contrôle du rythme dans la FA représente des coûts importants aux États-Unis. Traduit par Marc M Perreault

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