- Email: [email protected]
Use of Antiarrhythmic Medications in Medicare Part D Patients With an Implantable Cardioverter-Defibrillator and Ventricular Tachycardia
Use of Antiarrhythmic Medications in Medicare Part D Patients With an Implantable Cardioverter-Defibrillator and Ventricular Tachycardia Sean D. Pokorney, MD, MBAa,b,*, Xiaojuan Mi, PhDb, Bradley G. Hammill, DrPHb, Nancy M. Allen LaPointe, PharmD, MHSc, Lesley H. Curtis, PhDb, and Sana M. Al-Khatib, MD, MHSa,b Ventricular tachycardia (VT) is common in cardiomyopathy patients with an implantable cardioverter-defibrillator. This analysis evaluated antiarrhythmic medication use and change in use over time in patients with VT and structural heart disease. Query of Medicare claims identified patients with an implantable cardioverter-defibrillator and VT. Patients with atrial fibrillation or supraventricular tachycardia were excluded. Two cohorts were created of patients enrolled in Medicare Part D for the 12 months before 2007 and 2012. Patients were identified through a search for antiarrhythmic medication fills with a supply covering January 1 of the cohort year. Adjusted logistic regression modeling evaluated the association between patient characteristics and antiarrhythmic medication use. The 2007 (n [ 2,334) and 2012 (n [ 3,892) Medicare Part D cohorts had similar demographics: median age 76 years, 64%-67% male, and 87%-89% white. Of the 2007 cohort, 1,380 (59%) patients were on a beta blocker, and 484 (20.7%) were on an antiarrhythmic medication (70% amiodarone and 20% sotalol). Between 2007 and 2012, there was a statistically significant higher use of any antiarrhythmic medication (p [ 0.014), beta blockers (p <0.0001), mexiletine (p [ 0.005), and ranolazine (p <0.0001), while amiodarone use remained unchanged (p [ 0.53). After multivariable adjustment, male gender and renal disease were associated with higher antiarrhythmic medication use. In conclusion, although antiarrhythmic medication and beta blocker use in patients with VT increased over time, <1 in 4 patients were on an antiarrhythmic medication and only 65% of the patients were on a beta blocker. Ó 2017 Elsevier Inc. All rights reserved. (Am J Cardiol 2017;119:1401e1406) Randomized trials established the survival benefit of primary prevention implantable cardioverter-defibrillators (ICDs), among patients with low ejection fraction.1e4 The rate of appropriate ICD shocks for ventricular arrhythmias varied by study but was approximately 5% per year for patients with an ejection fraction 35% and class II or III heart failure.2 Although ICDs can prolong life by treating ventricular arrhythmias, appropriate ICD shocks have been associated with four-fold to six-fold higher risk of death relative to no appropriate therapy.5,6 Although this increased risk of death might be that ventricular arrhythmias were a marker of more advanced disease that itself increased the risk of death, direct damage to the heart by ICD shocks
could not be ruled out. Beyond the association with higher mortality, ICD shocks were associated with decreased functional status and quality of life.7 Some antiarrhythmic medications reduced ICD shocks, although these medications had high rates of discontinuation.8 Catheter ablation of ventricular tachycardia (VT) decreased ICD shocks and may have been associated with lower mortality.9e11 Outside clinical trials, there have been few reports with longitudinal follow-up on the prevalence of antiarrhythmic use for VT.1,12,13 This analysis evaluated the use of antiarrhythmic medications for VT in Medicare Part D patients with an ICD and cardiomyopathy. Methods
a Electrophysiology Section, Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina; b Duke Clinical Research Institute, Durham, North Carolina; and cPremier, Inc., Charlotte, North Carolina. Manuscript received October 10, 2016; revised manuscript received and accepted January 9, 2017. Funding: This work was supported by an independent investigatorinitiated research grant from Gilead Sciences (Foster City, California) to the Duke Clinical Research Institute. Role of the Funder/Sponsor: The funder was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. See page 1406 for disclosure information. *Corresponding author: Tel: (919) 668-8780; fax: (919) 681-7917. E-mail address: [email protected] (S.D. Pokorney).
0002-9149/17/$ - see front matter Ó 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2017.01.030
Data for this analysis were derived from a 5% sample of fee-for-service Medicare beneficiaries, including inpatient, outpatient, and carrier standard analytic files, Part D prescription drug data, and the denominator files. The inpatient files contained institutional claims for facility costs and include physician and hospital identifiers, admission and discharge dates, and diagnosis and procedure codes. The outpatient files contained claims from outpatient facility providers. The carrier files contained noninstitutional provider claims for services and included International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes, physician specialty, and place of service; Current Procedural Terminology codes; and dates of service. More than half of Medicare beneficiaries enrolled www.ajconline.org
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in Medicare Part D, a voluntary prescription drug benefit. The prescription drug files contained the generic names of prescription medications, number of days supplied, and information on Part D program enrollment and benefits. Denominator files included patient demographic characteristics, birth and death dates, and information about program eligibility and enrollment. We constructed 2 annual cohorts of prevalent VT patients with an ICD in place and cardiomyopathy: (1) those with prevalent VT as of January 1, 2007 and (2) those with prevalent VT as of January 1, 2012. From Medicare inpatient, outpatient, and carrier claims, we identified VT using ICD-9CM diagnosis code 427.69 or 427.1x, and ICD in situ using ICD-9-CM diagnosis code V45.02, during the previous calendar year (e.g., in 2006 for 2007 cohort). We limited the study population to patients 66 years or older, who had continuous Medicare fee-for-service enrollment (both Medicare Parts A and B) for previous 12 months and Medicare Part D enrollment on the index date (January 1 of the cohort year). We excluded patients who had a diagnosis of supraventricular tachycardia (427.0) or atrial fibrillation (427.31, 427.32), which might have been the reason for antiarrhythmic medication therapy. We also excluded patients with a diagnosis of hypertrophic cardiomyopathy (425.1x), long QT syndrome (426.82), or other specified congenital anomalies of the heart (746.89, which is the code used for short QT syndrome, arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, or catecholaminergic polymorphic VT). To describe the antiarrhythmic medication use among Medicare beneficiaries with VT and an ICD, we further required that patients be enrolled in a Medicare Part D plan for at least 3 months before January 1 of the cohort year. We searched for prescriptions of antiarrhythmic medications in the Part D event file using generic drug names. Patients were considered to be using a medication if they had a supply that covered January 1 of the cohort year, as determined by the date of the fill and the days supplied. Medications of interest were quinidine, procainamide, disopyramide, mexiletine, flecainide, propafenone, bucindolol, acebutolol, labetalol, nadolol, nebivolol, propranolol, metoprolol, carvedilol, atenolol, bisoprolol, amiodarone, sotalol, dofetilide, and ranolazine. Baseline characteristics and comorbidities (coronary artery disease, hypertension, diabetes mellitus, heart failure, renal disease, anemia, chronic obstructive pulmonary disease, cancer, previous percutaneous coronary intervention, and previous stroke; Appendix A) were ascertained from the Medicare denominator files and from the Medicare inpatient, outpatient, and carrier claims files in the 12 months preceding the index date. Baseline characteristics of the Medicare Part D and nonPart D populations were compared to assess generalizability. Data were presented as frequencies (percentages) for categorical variables and medians (interquartile range) for continuous variables. We calculated unadjusted rates of medication utilization by study cohorts. For the 2012 cohort, we compared the medication use rates by ischemic versus nonischemic VT. Differences between groups were tested by chi-square test for categorical variables and KruskaleWallis test for continuous variables. We estimated the unadjusted and adjusted association between baseline characteristics and antiarrhythmic
medication use with logistic regression models. We reported odds ratios and 95% confidence intervals. All models used a 2-tailed a ¼ 0.05 to establish statistical significance. Finally, we evaluated the change in antiarrhythmic medication use at the patient level over a 1-year period by comparing medication use as of January 1, 2012 to December 1, 2012. Version 9.4 of SAS was used for all analyses (SAS Institute, Inc., Cary, North Carolina). The Duke University institutional review board approved the study with waiver of consent. Results Within the 5% Medicare sample, the prevalence of VT among Part D patients with an ICD increased from 0.90 per 1,000 patients in 2007 to 1.35 per 1,000 patients in 2012. Among patients with VT and an ICD, patients with Medicare Part D coverage were clinically similar to those without Part D (Table 1). The exceptions were that patients with Part D were less likely to be male and more likely to be black (Table 1). Overall, catheter ablation for VT was uncommon. For years 2007 and 2012, patients with Part D, VT, and an ICD tended to be white, men with a history of coronary artery disease, hypertension, and heart failure (Table 1). Antiarrhythmic medications, including class I agents, class III agents, and ranolazine, were taken by 21% (n ¼ 484) of patients with Part D, VT, and an ICD. The number of patients taking an antiarrhythmic medication increased slightly to 23% (n ¼ 912) between 2007 and 2012 (p ¼ 0.014; Figure 1). Amiodarone was the most commonly used antiarrhythmic medication, accounting for 60% of antiarrhythmic medication use for 2007 and 70% for 2012. Class Ia and class Ic antiarrhythmic medications, which are contraindicated in this patient population, were used rarely (0.6% of the 2007 cohort and 0.5% of the 2012 cohort). The use of beta blockers increased from 59% (n ¼ 1,380) of patients from the 2007 cohort to 65% (2,538) of patients from the 2012 cohort (p <0.0001), and the use of mexiletine and ranolazine increased from 2007 (1% and 4%, respectively) to 2012 (2% and 5%, respectively; p ¼ 0.005 and p <0.0001, respectively). Within the 2012 cohort, the rates of antiarrhythmic medication and beta-blocker use were similar for patients with ischemic and nonischemic etiologies (Figure 2). The one exception was ranolazine, which was used more commonly in patients with ischemic VT relative to nonischemic VT (1.9% vs 0.3% respectively, p ¼ 0.006). Among the 6,226 patients with Medicare Part D in 2007 or 2012, VT, and an ICD, there were 1,396 (22%) patients treated with an antiarrhythmic medication. Patients treated with an antiarrhythmic medication were more likely to be male and less likely to be black (Table 2). Patients on antiarrhythmic medications tended to have more heart failure, renal disease, and chronic obstructive pulmonary disease, while having less anemia, as compared with patients not on antiarrhythmic medications. After multivariable adjustment male sex and renal disease were associated with higher odds of antiarrhythmic medication use (Table 3). Lower odds of antiarrhythmic medication use were associated with black race, anemia, and previous stroke (Table 3).
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Table 1 Baseline characteristics of patients with ventricular tachycardia and an implantable cardioverter-defibrillator by Part D enrollment status Variable
2007 Cohort Without Part D Enrollment (n¼3,538)
Age (median, Q1, Q3) Men White Black Non-white, non-black Coronary artery disease* Hypertension* Diabetes mellitus* Heart failure* Renal disease* Anemia* Chronic obstructive pulmonary disease* Cancer* Prior percutaneous coronary intervention* Prior coronary bypass* Prior stroke* Ventricular tachycardia ablation*
76.0 2,815 3,308 165 65 3,264 3,006 1,493 3,080 947 468 1,419 685 82 11 619 10
(72.0-81.0) (79.6%) (93.5%) (4.7%) (1.8%) (92.3%) (85.0%) (42.2%) (87.1%) (26.8%) (13.2%) (40.1%) (19.4%) (2.3%) (0.3%) (17.5%) (0.3%)
2012 Cohort
With Part D Enrollment (n¼2,334) 76.0 1,499 2,065 176 93 2,158 2,070 1,042 2,059 636 359 1,020 390 50 10 396 10
(71.0-81.0) (64.2%) (88.5%) (7.5%) (4.0%) (92.5%) (88.7%) (44.6%) (88.2%) (27.2%) (15.4%) (43.7%) (16.7%) (2.1%) (0.3%) (17.0%) (0.3%)
P-value
0.005 <0.001 <0.001
0.77 <0.001 0.06 0.19 0.68 0.020 0.006 0.010 0.66 0.83 0.60 0.047
Without Part D Enrollment (n¼3,742) 78.0 2,939 3,428 248 66 3,372 3,404 1,733 3,268 1,285 492 1,603 770 35 10 638 10
(72.0-83.0) (78.5%) (91.6%) (6.6%) (1.8%) (90.1%) (91.0%) (46.3%) (87.3%) (34.3%) (13.1%) (42.8%) (20.6%) (0.9%) (0.3%) (17.0%) (0.3%)
With Part D Enrollment (n¼3,892) 76.0 2,615 3,384 363 145 3,502 3,602 1,935 3,489 1,429 502 1,862 681 43 10 720 10
(71.0-82.0) (67.2%) (86.9%) (9.3%) (3.7%) (90.0%) (92.5%) (49.7%) (89.6%) (36.7%) (12.9%) (47.8%) (17.5%) (1.1%) (0.3%) (18.5%) (0.3%)
P-value
<0.001 <0.001 <0.001
0.85 0.012 0.003 0.002 0.030 0.75 <0.001 0.001 0.46 0.005 0.10 0.61
CMS requires that the specific data for any variable with 10 patients be suppressed and labeled as 10. CMS ¼ Centers for Medicare and Medicaid Services. * Defined by ICD-9 codes within the claims data.
Figure 1. Unadjusted medication rates for Medicare Part D patients with VT and ICD. *p <0.005, #p ¼ 0.01. CMS requires that the specific data for any variable with 10 patients be suppressed and labeled as 10. CMS ¼ Centers for Medicare and Medicaid Services.
Over the course of the 2012 calendar year, the majority of Medicare Part D patients were maintained on the same antiarrhythmic medication at the same dose (55%, n ¼ 506), while an additional 14% (n ¼ 132) of patients stayed on the same antiarrhythmic medication with changes to the dose (7% decrease and 3% increase) or with the addition of another antiarrhythmic medication (4%). Over that same 1-year timeframe, 30% of patients discontinued their antiarrhythmic medication (Figure 3).
Discussion Patients with cardiovascular disease are living longer, therefore downstream sequelae, such as implantation of ICDs and VT, have increased. This study found that <1 in 4 patients with structural heart disease and VT were taking an antiarrhythmic medication, and only 65% of patients with VT were taking a beta blocker. Among patients taking an antiarrhythmic medication, approximately 2/3 of the patients
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Figure 2. Unadjusted medication rates for Medicare Part D patients with ischemic and nonischemic VT in 2012 cohort. *p <0.01. CMS requires that the specific data for any variable with 10 patients be suppressed and labeled as 10. CMS ¼ Centers for Medicare and Medicaid Services.
Table 2 Patient characteristics stratified by antiarrhythmic drug use Variable
Antiarrhythmic Drug No (n¼4,830)
Age, median (Q1, Q3) Men Black Coronary artery disease * Hypertension * Diabetes mellitus * Heart failure * Renal disease * Anemia * Chronic obstructive pulmonary disease * Cancer * Prior percutaneous coronary intervention * Prior coronary bypass * Prior Stroke * Prior ventricular tachycardia ablation *
76.0 3,135 448 4,384 4,401 2,316 4,281 1,536 747 2,174
p-value
Yes (n¼1,396)
(71.1-81.0) 76.0 (71.0-81.0) (64.9%) 979 (70.1%) (9.3%) 91 (6.5%) (90.8%) 1,276 (91.4%) (91.1%) 1,271 (91.0%) (48.0%) 661 (47.3%) (88.6%) 1,267 (90.8%) (31.8%) 529 (37.9%) (15.5%) 114 (8.2%) (45.0%) 708 (50.7%)
0.047 <0.001 0.006 0.47 0.93 0.69 0.025 <0.001 <0.001 <0.001
848 (17.6%) 76 (1.6%)
223 (16.0%) 17 (1.2%)
0.17 0.33
10 (0.3%) 896 (18.6%) 10 (0.3%)
10 (0.3%) 220 (15.8%) 10 (0.3%)
0.11 0.017 0.002
* Defined by ICD-9 codes within the claims data.
were prescribed amiodarone. Nearly 1 in 3 patients taking an antiarrhythmic medication discontinued the medication over the course of 1 year. The prevalence of VT among Medicare Part D patients with an ICD increased by 50% between 2007 and 2012 (0.90 to 1.35 per 1,000 patients). Some reports note that antiarrhythmic medications for ventricular arrhythmias are prescribed for 40%-70% of ICD patients.14e18 Clinical trial data suggested lower rates of antiarrhythmic medication use.1,12 One recent study analyzed the National Cardiovascular Data Registry - ICD Registry finding that
approximately 15% of newly implanted ICD patients were discharged on antiarrhythmic medications, but this included patients with atrial fibrillation and supraventricular tachycardia.13 The rates of antiarrhythmic medication use were higher among atrial fibrillation patients and were similar to secondary prevention ICD patients, suggesting that a large portion of antiarrhythmic medications were prescribed for supraventricular arrhythmias. The only data on patients without atrial fibrillation were in patients with primary prevention ICDs, who were on an antiarrhythmic medication in <5% of the cases.13 We found a higher rate of antiarrhythmic medication use of over 20%, despite excluding patients with atrial fibrillation or supraventricular tachycardia; however, the ICD Registry analysis was based on medications at the time of ICD implantation, while our study reflected ventricular arrhythmias noted on device interrogations. The ICD Registry evaluation of antiarrhythmic medications noted that over 80% of patients were prescribed a beta blocker at discharge.13 Similarly, an analysis of Medicare Part D prescription data in patients before primary prevention ICD placement identified 81% use of beta blockers in the 3 months before ICD implantation,19 which was meaningfully higher than the 65% seen in our analysis, despite both analyses using Medicare Part D prescription data. All analyses found lower rates of beta-blocker use than the >90% among heart failure patients in Get With the Guidelines.20 These findings raise concern that beta blockers may be underused in patients with VT and structural heart disease, despite beta blockers decreasing sudden death.21 A possible explanation for the low use of beta blockers in our analysis was that these medications may be filled outside Medicare Part D plans, such as through the $4 plan, which would not be captured in our dataset. However, a previous analysis of cardiovascular medications found that only 6% of prescriptions were filled outside Medicare Part D,22 and the rate of beta-blocker use captured by Medicare Part D
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Table 3 Association between patient characteristics and use of class I or class III antiarrhythmic medications or ranolazine (n ¼ 6,226) Unadjusted OR (95% CI) Age group (ref: 66-69) (years) 70-74 75-79 80þ Male (reference: female) Black (reference: white) Coronary artery disease * Hypertension * Diabetes Mellitus * Heart failure * Renal disease * Anemia * Chronic obstructive pulmonary disease * Cancer * Prior percutaneous coronary intervention * Prior stroke *
1.02 1.04 0.88 1.27 0.68 1.08 0.99 0.98 1.26 1.31 0.49 1.26 0.89 0.77 0.82
(0.85, (0.86, (0.74, (1.12, (0.54, (0.88, (0.80, (0.87, (1.03, (1.16, (0.40, (1.12, (0.76, (0.45, (0.70,
1.23) 1.24) 1.05) 1.44) 0.86) 1.34) 1.22) 1.10) 1.54) 1.48) 0.60) 1.42) 1.05) 1.31) 0.97)
Adjusted p-value 0.79 0.70 0.15 <0.001 0.001 0.47 0.93 0.69 0.025 <0.001 <0.001 <0.001 0.17 0.34 0.017
OR (95% CI) 1.05 1.07 0.91 1.22 0.71 1.00 0.98 0.96 1.18 1.39 0.48 1.23 0.89 0.83 0.79
(0.87, (0.89, (0.76, (1.06, (0.56, (0.80, (0.79, (0.85, (0.96, (1.21, (0.39, (1.08, (0.75, (0.48, (0.67,
1.26) 1.29) 1.09) 1.39) 0.90) 1.25) 1.22) 1.09) 1.45) 1.58) 0.59) 1.39) 1.05) 1.42) 0.93)
p-value 0.64 0.47 0.29 0.004 0.005 0.99 0.84 0.58 0.12 <0.001 <0.001 0.001 0.16 0.49 0.006
All co-variates in the adjusted model are listed in the table. * Defined by ICD-9 codes within the claims data.
Figure 3. Changes in antiarrhythmic medications among patients alive from January 1, 2012 to December 31, 2012.
was still higher in the previously published analysis of primary prevention ICD patients.19 Among patients treated with an antiarrhythmic medication, amiodarone was used in approximately 2/3 of patients in our analysis. Randomized trials of amiodarone and sotalol have demonstrated a modest decrease in appropriate ICD shocks, although no consistent association with lower mortality.8,23e26 Ranolazine at the time of non-ST-elevation myocardial infarction reduced VT within 7 days of randomization (5% vs 8%, p <0.001).27 There have been no randomized trial data on mexiletine in VT, but our analysis found that mexiletine and ranolazine use increased from 2007 to 2012. Even among patients treated with an antiarrhythmic medication, there are high discontinuation rates because of adverse medication effects and inefficacy. In this study, 30% of patients on an antiarrhythmic medication discontinued that medication within 1 year. Unfortunately, the reason for discontinuation in our analysis is not known. These data are consistent with discontinuation rates from amiodarone trials
ranging from 27% over a median of 3.8 years to 39% over 1.8 years.24e26 In the optimal pharmacological therapy in cardioverter defibrillator patients (OPTIC) trial, the discontinuation rates of amiodarone and sotalol were high even during the first year: 18% and 24%, respectively.8 Although this analysis represents a large, national cohort of patients from Medicare Part D claims data, several limitations need to be acknowledged. One of the major advantages of claims data is that it reflects an unselected patient population, but inaccurate coding or undercoding could affect the results. In this analysis, it was unknown whether the antiarrhythmic medication was specifically prescribed for VT, but patients with atrial fibrillation or supraventricular tachycardia were excluded. Even within this more narrowly defined patient population, the ICD-9 code for VT does not differentiate nonsustained VT from sustained VT. The indication for ICD implantation (primary vs secondary prevention) was not available. Therefore, the appropriateness of antiarrhythmic drug use was not known. The data presented in the present study were for medication fills, and they may not be representative of provider prescribing patterns. The findings in this older population may not be generalizable to a younger patient population. Although our analysis showed that the clinical characteristics are similar for patients with VT and an ICD enrolled in and not enrolled in Medicare Part D, we were not able to verify the antiarrhythmic medication use of non-Medicare Part D patients. Finally, no outcomes data were presented, as these analyses would be confounded in this Medicare claims-based dataset. Although antiarrhythmic medication and beta-blocker use in patients with VT increased over time, <1 in 4 patients were on an antiarrhythmic medication and only 65% of patients were on a beta blocker. Among those patients on an antiarrhythmic medication, nearly 1 in 3 patients had discontinued the medication at 1 year.
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Disclosures Dr. Pokorney received grants or research support from AstraZeneca, London, United Kingdom, Gilead Sciences, Foster City, California, and Boston Scientific, Marlborough, Massachusetts, and received honoraria for consulting from Medtronic, Dublin, Republic of Ireland and Boston Scientific. All other authors have no conflicts of interest to disclose.
12.
13.
Supplementary Data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j. amjcard.2017.01.030. 1. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877e883. 2. Bardy GH, Lee KL, Mark DB, Poole JE, Packer DL, Boineau R, Domanski M, Troutman C, Anderson J, Johnson G, McNulty SE, ClappChanning N, Davidson-Ray LD, Fraulo ES, Fishbein DP, Luceri RM, Ip JH. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225e237. 3. Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999;341:1882e1890. 4. Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D, Brown MW, Heo M. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996;335:1933e1940. 5. Moss AJ, Greenberg H, Case RB, Zareba W, Hall WJ, Brown MW, Daubert JP, McNitt S, Andrews ML, Elkin AD. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Circulation 2004;110:3760e3765. 6. Poole JE, Johnson GW, Hellkamp AS, Anderson J, Callans DJ, Raitt MH, Reddy RK, Marchlinski FE, Yee R, Guarnieri T, Talajic M, Wilber DJ, Fishbein DP, Packer DL, Mark DB, Lee KL, Bardy GH. Prognostic importance of defibrillator shocks in patients with heart failure. N Engl J Med 2008;359:1009e1017. 7. Schron EB, Exner DV, Yao Q, Jenkins LS, Steinberg JS, Cook JR, Kutalek SP, Friedman PL, Bubien RS, Page RL, Powell J. Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation 2002;105:589e594. 8. Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S, Fain ES, Thorpe K, Champagne J, Talajic M, Coutu B, Gronefeld GC, Hohnloser SH. Comparison of beta-blockers, amiodarone plus betablockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 2006;295:165e171. 9. Calkins H, Epstein A, Packer D, Arria AM, Hummel J, Gilligan DM, Trusso J, Carlson M, Luceri R, Kopelman H, Wilber D, Wharton JM, Stevenson W. Catheter ablation of ventricular tachycardia in patients with structural heart disease using cooled radiofrequency energy: results of a prospective multicenter study. Cooled RF Multi Center Investigators Group. J Am Coll Cardiol 2000;35:1905e1914. 10. Stevenson WG, Wilber DJ, Natale A, Jackman WM, Marchlinski FE, Talbert T, Gonzalez MD, Worley SJ, Daoud EG, Hwang C, Schuger C, Bump TE, Jazayeri M, Tomassoni GF, Kopelman HA, Soejima K, Nakagawa H. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation 2008;118:2773e2782. 11. Dinov B, Arya A, Bertagnolli L, Schirripa V, Schoene K, Sommer P, Bollmann A, Rolf S, Hindricks G. Early referral for ablation of
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scar-related ventricular tachycardia is associated with improved acute and long-term outcomes: results from the Heart Center of Leipzig ventricular tachycardia registry. Circ Arrhythm Electrophysiol 2014;7: 1144e1151. Steinberg JS, Martins J, Sadanandan S, Goldner B, Menchavez E, Domanski M, Russo A, Tullo N, Hallstrom A; AVID Investigators. Antiarrhythmic drug use in the implantable defibrillator arm of the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study. Am Heart J 2001;142:520e529. Dev S, Peterson PN, Wang Y, Curtis JP, Varosy PD, Masoudi FA. Prevalence, correlates, and temporal trends in antiarrhythmic drug use at discharge after implantable cardioverter defibrillator placement (from the National Cardiovascular Data Registry [NCDR]). Am J Cardiol 2014;113:314e320. Winkle RA, Mead RH, Ruder MA, Gaudiani VA, Smith NA, Buch WS, Schmidt P, Shipman T. Long-term outcome with the automatic implantable cardioverter-defibrillator. J Am Coll Cardiol 1989;13:1353e1361. Echt DS, Armstrong K, Schmidt P, Oyer PE, Stinson EB, Winkle RA. Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator. Circulation 1985;71: 289e296. Thomas AC, Moser SA, Smutka ML, Wilson PA. Implantable defibrillation: eight years clinical experience. Pacing Clin Eectrophysiol 1988;11:2053e2058. Kelly PA, Cannom DS, Garan H, Mirabal GS, Harthorne JW, Hurvitz RJ, Vlahakes GJ, Jacobs ML, Ilvento JP, Buckley MJ, Ruskin JN. The automatic implantable cardioverter-defibrillator: efficacy, complications and survival in patients with malignant ventricular arrhythmias. J Am Coll Cardiol 1988;11:1278e1286. Manz M, Jung W, Luderitz B. Interactions between drugs and devices: experimental and clinical studies. Am Heart J 1994;127:978e984. Roth GA, Poole JE, Zaha R, Zhou W, Skinner J, Morden NE. Use of guideline-directed medications for heart failure before cardioverterdefibrillator implantation. J Am Coll Cardiol 2016;67:1062e1069. Krantz MJ, Ambardekar AV, Kaltenbach L, Hernandez AF, Heidenreich PA, Fonarow GC; Get With the Guidelines Steering Committee and Hospitals. Patterns and predictors of evidence-based medication continuation among hospitalized heart failure patients (from Get With the Guidelines-Heart Failure). Am J Cardiol 2011;107:1818e1823. McMurray J, Kober L, Robertson M, Dargie H, Colucci W, LopezSendon J, Remme W, Sharpe DN, Ford I. Antiarrhythmic effect of carvedilol after acute myocardial infarction: results of the Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) trial. J Am Coll Cardiol 2005;45:525e530. Roberto PN, Stuart B. Out-of-plan medication in Medicare Part D. Am J Manag Care 2014;20:743e748. Pacifico A, Hohnloser SH, Williams JH, Tao B, Saksena S, Henry PD, Prystowsky EN. Prevention of implantable-defibrillator shocks by treatment with sotalol. N Engl J Med 1999;340:1855e1862. Julian DG, Camm AJ, Frangin G, Janse MJ, Munoz A, Schwartz PJ, Simon P. Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. Lancet 1997;349:667e674. Cairns JA, Connolly SJ, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Lancet 1997;349:675e682. Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, Massie BM, Colling C, Lazzeri D. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 1995;333:77e82. Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM, Molhoek P, Verheugt FW, Gersh BJ, McCabe CH, Braunwald E. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation 2007;116:1647e1652.
could not be ruled out. Beyond the association with higher mortality, ICD shocks were associated with decreased functional status and quality of life.7 Some antiarrhythmic medications reduced ICD shocks, although these medications had high rates of discontinuation.8 Catheter ablation of ventricular tachycardia (VT) decreased ICD shocks and may have been associated with lower mortality.9e11 Outside clinical trials, there have been few reports with longitudinal follow-up on the prevalence of antiarrhythmic use for VT.1,12,13 This analysis evaluated the use of antiarrhythmic medications for VT in Medicare Part D patients with an ICD and cardiomyopathy. Methods
a Electrophysiology Section, Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina; b Duke Clinical Research Institute, Durham, North Carolina; and cPremier, Inc., Charlotte, North Carolina. Manuscript received October 10, 2016; revised manuscript received and accepted January 9, 2017. Funding: This work was supported by an independent investigatorinitiated research grant from Gilead Sciences (Foster City, California) to the Duke Clinical Research Institute. Role of the Funder/Sponsor: The funder was not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. See page 1406 for disclosure information. *Corresponding author: Tel: (919) 668-8780; fax: (919) 681-7917. E-mail address: [email protected] (S.D. Pokorney).
0002-9149/17/$ - see front matter Ó 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2017.01.030
Data for this analysis were derived from a 5% sample of fee-for-service Medicare beneficiaries, including inpatient, outpatient, and carrier standard analytic files, Part D prescription drug data, and the denominator files. The inpatient files contained institutional claims for facility costs and include physician and hospital identifiers, admission and discharge dates, and diagnosis and procedure codes. The outpatient files contained claims from outpatient facility providers. The carrier files contained noninstitutional provider claims for services and included International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes, physician specialty, and place of service; Current Procedural Terminology codes; and dates of service. More than half of Medicare beneficiaries enrolled www.ajconline.org
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in Medicare Part D, a voluntary prescription drug benefit. The prescription drug files contained the generic names of prescription medications, number of days supplied, and information on Part D program enrollment and benefits. Denominator files included patient demographic characteristics, birth and death dates, and information about program eligibility and enrollment. We constructed 2 annual cohorts of prevalent VT patients with an ICD in place and cardiomyopathy: (1) those with prevalent VT as of January 1, 2007 and (2) those with prevalent VT as of January 1, 2012. From Medicare inpatient, outpatient, and carrier claims, we identified VT using ICD-9CM diagnosis code 427.69 or 427.1x, and ICD in situ using ICD-9-CM diagnosis code V45.02, during the previous calendar year (e.g., in 2006 for 2007 cohort). We limited the study population to patients 66 years or older, who had continuous Medicare fee-for-service enrollment (both Medicare Parts A and B) for previous 12 months and Medicare Part D enrollment on the index date (January 1 of the cohort year). We excluded patients who had a diagnosis of supraventricular tachycardia (427.0) or atrial fibrillation (427.31, 427.32), which might have been the reason for antiarrhythmic medication therapy. We also excluded patients with a diagnosis of hypertrophic cardiomyopathy (425.1x), long QT syndrome (426.82), or other specified congenital anomalies of the heart (746.89, which is the code used for short QT syndrome, arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, or catecholaminergic polymorphic VT). To describe the antiarrhythmic medication use among Medicare beneficiaries with VT and an ICD, we further required that patients be enrolled in a Medicare Part D plan for at least 3 months before January 1 of the cohort year. We searched for prescriptions of antiarrhythmic medications in the Part D event file using generic drug names. Patients were considered to be using a medication if they had a supply that covered January 1 of the cohort year, as determined by the date of the fill and the days supplied. Medications of interest were quinidine, procainamide, disopyramide, mexiletine, flecainide, propafenone, bucindolol, acebutolol, labetalol, nadolol, nebivolol, propranolol, metoprolol, carvedilol, atenolol, bisoprolol, amiodarone, sotalol, dofetilide, and ranolazine. Baseline characteristics and comorbidities (coronary artery disease, hypertension, diabetes mellitus, heart failure, renal disease, anemia, chronic obstructive pulmonary disease, cancer, previous percutaneous coronary intervention, and previous stroke; Appendix A) were ascertained from the Medicare denominator files and from the Medicare inpatient, outpatient, and carrier claims files in the 12 months preceding the index date. Baseline characteristics of the Medicare Part D and nonPart D populations were compared to assess generalizability. Data were presented as frequencies (percentages) for categorical variables and medians (interquartile range) for continuous variables. We calculated unadjusted rates of medication utilization by study cohorts. For the 2012 cohort, we compared the medication use rates by ischemic versus nonischemic VT. Differences between groups were tested by chi-square test for categorical variables and KruskaleWallis test for continuous variables. We estimated the unadjusted and adjusted association between baseline characteristics and antiarrhythmic
medication use with logistic regression models. We reported odds ratios and 95% confidence intervals. All models used a 2-tailed a ¼ 0.05 to establish statistical significance. Finally, we evaluated the change in antiarrhythmic medication use at the patient level over a 1-year period by comparing medication use as of January 1, 2012 to December 1, 2012. Version 9.4 of SAS was used for all analyses (SAS Institute, Inc., Cary, North Carolina). The Duke University institutional review board approved the study with waiver of consent. Results Within the 5% Medicare sample, the prevalence of VT among Part D patients with an ICD increased from 0.90 per 1,000 patients in 2007 to 1.35 per 1,000 patients in 2012. Among patients with VT and an ICD, patients with Medicare Part D coverage were clinically similar to those without Part D (Table 1). The exceptions were that patients with Part D were less likely to be male and more likely to be black (Table 1). Overall, catheter ablation for VT was uncommon. For years 2007 and 2012, patients with Part D, VT, and an ICD tended to be white, men with a history of coronary artery disease, hypertension, and heart failure (Table 1). Antiarrhythmic medications, including class I agents, class III agents, and ranolazine, were taken by 21% (n ¼ 484) of patients with Part D, VT, and an ICD. The number of patients taking an antiarrhythmic medication increased slightly to 23% (n ¼ 912) between 2007 and 2012 (p ¼ 0.014; Figure 1). Amiodarone was the most commonly used antiarrhythmic medication, accounting for 60% of antiarrhythmic medication use for 2007 and 70% for 2012. Class Ia and class Ic antiarrhythmic medications, which are contraindicated in this patient population, were used rarely (0.6% of the 2007 cohort and 0.5% of the 2012 cohort). The use of beta blockers increased from 59% (n ¼ 1,380) of patients from the 2007 cohort to 65% (2,538) of patients from the 2012 cohort (p <0.0001), and the use of mexiletine and ranolazine increased from 2007 (1% and 4%, respectively) to 2012 (2% and 5%, respectively; p ¼ 0.005 and p <0.0001, respectively). Within the 2012 cohort, the rates of antiarrhythmic medication and beta-blocker use were similar for patients with ischemic and nonischemic etiologies (Figure 2). The one exception was ranolazine, which was used more commonly in patients with ischemic VT relative to nonischemic VT (1.9% vs 0.3% respectively, p ¼ 0.006). Among the 6,226 patients with Medicare Part D in 2007 or 2012, VT, and an ICD, there were 1,396 (22%) patients treated with an antiarrhythmic medication. Patients treated with an antiarrhythmic medication were more likely to be male and less likely to be black (Table 2). Patients on antiarrhythmic medications tended to have more heart failure, renal disease, and chronic obstructive pulmonary disease, while having less anemia, as compared with patients not on antiarrhythmic medications. After multivariable adjustment male sex and renal disease were associated with higher odds of antiarrhythmic medication use (Table 3). Lower odds of antiarrhythmic medication use were associated with black race, anemia, and previous stroke (Table 3).
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Table 1 Baseline characteristics of patients with ventricular tachycardia and an implantable cardioverter-defibrillator by Part D enrollment status Variable
2007 Cohort Without Part D Enrollment (n¼3,538)
Age (median, Q1, Q3) Men White Black Non-white, non-black Coronary artery disease* Hypertension* Diabetes mellitus* Heart failure* Renal disease* Anemia* Chronic obstructive pulmonary disease* Cancer* Prior percutaneous coronary intervention* Prior coronary bypass* Prior stroke* Ventricular tachycardia ablation*
76.0 2,815 3,308 165 65 3,264 3,006 1,493 3,080 947 468 1,419 685 82 11 619 10
(72.0-81.0) (79.6%) (93.5%) (4.7%) (1.8%) (92.3%) (85.0%) (42.2%) (87.1%) (26.8%) (13.2%) (40.1%) (19.4%) (2.3%) (0.3%) (17.5%) (0.3%)
2012 Cohort
With Part D Enrollment (n¼2,334) 76.0 1,499 2,065 176 93 2,158 2,070 1,042 2,059 636 359 1,020 390 50 10 396 10
(71.0-81.0) (64.2%) (88.5%) (7.5%) (4.0%) (92.5%) (88.7%) (44.6%) (88.2%) (27.2%) (15.4%) (43.7%) (16.7%) (2.1%) (0.3%) (17.0%) (0.3%)
P-value
0.005 <0.001 <0.001
0.77 <0.001 0.06 0.19 0.68 0.020 0.006 0.010 0.66 0.83 0.60 0.047
Without Part D Enrollment (n¼3,742) 78.0 2,939 3,428 248 66 3,372 3,404 1,733 3,268 1,285 492 1,603 770 35 10 638 10
(72.0-83.0) (78.5%) (91.6%) (6.6%) (1.8%) (90.1%) (91.0%) (46.3%) (87.3%) (34.3%) (13.1%) (42.8%) (20.6%) (0.9%) (0.3%) (17.0%) (0.3%)
With Part D Enrollment (n¼3,892) 76.0 2,615 3,384 363 145 3,502 3,602 1,935 3,489 1,429 502 1,862 681 43 10 720 10
(71.0-82.0) (67.2%) (86.9%) (9.3%) (3.7%) (90.0%) (92.5%) (49.7%) (89.6%) (36.7%) (12.9%) (47.8%) (17.5%) (1.1%) (0.3%) (18.5%) (0.3%)
P-value
<0.001 <0.001 <0.001
0.85 0.012 0.003 0.002 0.030 0.75 <0.001 0.001 0.46 0.005 0.10 0.61
CMS requires that the specific data for any variable with 10 patients be suppressed and labeled as 10. CMS ¼ Centers for Medicare and Medicaid Services. * Defined by ICD-9 codes within the claims data.
Figure 1. Unadjusted medication rates for Medicare Part D patients with VT and ICD. *p <0.005, #p ¼ 0.01. CMS requires that the specific data for any variable with 10 patients be suppressed and labeled as 10. CMS ¼ Centers for Medicare and Medicaid Services.
Over the course of the 2012 calendar year, the majority of Medicare Part D patients were maintained on the same antiarrhythmic medication at the same dose (55%, n ¼ 506), while an additional 14% (n ¼ 132) of patients stayed on the same antiarrhythmic medication with changes to the dose (7% decrease and 3% increase) or with the addition of another antiarrhythmic medication (4%). Over that same 1-year timeframe, 30% of patients discontinued their antiarrhythmic medication (Figure 3).
Discussion Patients with cardiovascular disease are living longer, therefore downstream sequelae, such as implantation of ICDs and VT, have increased. This study found that <1 in 4 patients with structural heart disease and VT were taking an antiarrhythmic medication, and only 65% of patients with VT were taking a beta blocker. Among patients taking an antiarrhythmic medication, approximately 2/3 of the patients
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Figure 2. Unadjusted medication rates for Medicare Part D patients with ischemic and nonischemic VT in 2012 cohort. *p <0.01. CMS requires that the specific data for any variable with 10 patients be suppressed and labeled as 10. CMS ¼ Centers for Medicare and Medicaid Services.
Table 2 Patient characteristics stratified by antiarrhythmic drug use Variable
Antiarrhythmic Drug No (n¼4,830)
Age, median (Q1, Q3) Men Black Coronary artery disease * Hypertension * Diabetes mellitus * Heart failure * Renal disease * Anemia * Chronic obstructive pulmonary disease * Cancer * Prior percutaneous coronary intervention * Prior coronary bypass * Prior Stroke * Prior ventricular tachycardia ablation *
76.0 3,135 448 4,384 4,401 2,316 4,281 1,536 747 2,174
p-value
Yes (n¼1,396)
(71.1-81.0) 76.0 (71.0-81.0) (64.9%) 979 (70.1%) (9.3%) 91 (6.5%) (90.8%) 1,276 (91.4%) (91.1%) 1,271 (91.0%) (48.0%) 661 (47.3%) (88.6%) 1,267 (90.8%) (31.8%) 529 (37.9%) (15.5%) 114 (8.2%) (45.0%) 708 (50.7%)
0.047 <0.001 0.006 0.47 0.93 0.69 0.025 <0.001 <0.001 <0.001
848 (17.6%) 76 (1.6%)
223 (16.0%) 17 (1.2%)
0.17 0.33
10 (0.3%) 896 (18.6%) 10 (0.3%)
10 (0.3%) 220 (15.8%) 10 (0.3%)
0.11 0.017 0.002
* Defined by ICD-9 codes within the claims data.
were prescribed amiodarone. Nearly 1 in 3 patients taking an antiarrhythmic medication discontinued the medication over the course of 1 year. The prevalence of VT among Medicare Part D patients with an ICD increased by 50% between 2007 and 2012 (0.90 to 1.35 per 1,000 patients). Some reports note that antiarrhythmic medications for ventricular arrhythmias are prescribed for 40%-70% of ICD patients.14e18 Clinical trial data suggested lower rates of antiarrhythmic medication use.1,12 One recent study analyzed the National Cardiovascular Data Registry - ICD Registry finding that
approximately 15% of newly implanted ICD patients were discharged on antiarrhythmic medications, but this included patients with atrial fibrillation and supraventricular tachycardia.13 The rates of antiarrhythmic medication use were higher among atrial fibrillation patients and were similar to secondary prevention ICD patients, suggesting that a large portion of antiarrhythmic medications were prescribed for supraventricular arrhythmias. The only data on patients without atrial fibrillation were in patients with primary prevention ICDs, who were on an antiarrhythmic medication in <5% of the cases.13 We found a higher rate of antiarrhythmic medication use of over 20%, despite excluding patients with atrial fibrillation or supraventricular tachycardia; however, the ICD Registry analysis was based on medications at the time of ICD implantation, while our study reflected ventricular arrhythmias noted on device interrogations. The ICD Registry evaluation of antiarrhythmic medications noted that over 80% of patients were prescribed a beta blocker at discharge.13 Similarly, an analysis of Medicare Part D prescription data in patients before primary prevention ICD placement identified 81% use of beta blockers in the 3 months before ICD implantation,19 which was meaningfully higher than the 65% seen in our analysis, despite both analyses using Medicare Part D prescription data. All analyses found lower rates of beta-blocker use than the >90% among heart failure patients in Get With the Guidelines.20 These findings raise concern that beta blockers may be underused in patients with VT and structural heart disease, despite beta blockers decreasing sudden death.21 A possible explanation for the low use of beta blockers in our analysis was that these medications may be filled outside Medicare Part D plans, such as through the $4 plan, which would not be captured in our dataset. However, a previous analysis of cardiovascular medications found that only 6% of prescriptions were filled outside Medicare Part D,22 and the rate of beta-blocker use captured by Medicare Part D
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Table 3 Association between patient characteristics and use of class I or class III antiarrhythmic medications or ranolazine (n ¼ 6,226) Unadjusted OR (95% CI) Age group (ref: 66-69) (years) 70-74 75-79 80þ Male (reference: female) Black (reference: white) Coronary artery disease * Hypertension * Diabetes Mellitus * Heart failure * Renal disease * Anemia * Chronic obstructive pulmonary disease * Cancer * Prior percutaneous coronary intervention * Prior stroke *
1.02 1.04 0.88 1.27 0.68 1.08 0.99 0.98 1.26 1.31 0.49 1.26 0.89 0.77 0.82
(0.85, (0.86, (0.74, (1.12, (0.54, (0.88, (0.80, (0.87, (1.03, (1.16, (0.40, (1.12, (0.76, (0.45, (0.70,
1.23) 1.24) 1.05) 1.44) 0.86) 1.34) 1.22) 1.10) 1.54) 1.48) 0.60) 1.42) 1.05) 1.31) 0.97)
Adjusted p-value 0.79 0.70 0.15 <0.001 0.001 0.47 0.93 0.69 0.025 <0.001 <0.001 <0.001 0.17 0.34 0.017
OR (95% CI) 1.05 1.07 0.91 1.22 0.71 1.00 0.98 0.96 1.18 1.39 0.48 1.23 0.89 0.83 0.79
(0.87, (0.89, (0.76, (1.06, (0.56, (0.80, (0.79, (0.85, (0.96, (1.21, (0.39, (1.08, (0.75, (0.48, (0.67,
1.26) 1.29) 1.09) 1.39) 0.90) 1.25) 1.22) 1.09) 1.45) 1.58) 0.59) 1.39) 1.05) 1.42) 0.93)
p-value 0.64 0.47 0.29 0.004 0.005 0.99 0.84 0.58 0.12 <0.001 <0.001 0.001 0.16 0.49 0.006
All co-variates in the adjusted model are listed in the table. * Defined by ICD-9 codes within the claims data.
Figure 3. Changes in antiarrhythmic medications among patients alive from January 1, 2012 to December 31, 2012.
was still higher in the previously published analysis of primary prevention ICD patients.19 Among patients treated with an antiarrhythmic medication, amiodarone was used in approximately 2/3 of patients in our analysis. Randomized trials of amiodarone and sotalol have demonstrated a modest decrease in appropriate ICD shocks, although no consistent association with lower mortality.8,23e26 Ranolazine at the time of non-ST-elevation myocardial infarction reduced VT within 7 days of randomization (5% vs 8%, p <0.001).27 There have been no randomized trial data on mexiletine in VT, but our analysis found that mexiletine and ranolazine use increased from 2007 to 2012. Even among patients treated with an antiarrhythmic medication, there are high discontinuation rates because of adverse medication effects and inefficacy. In this study, 30% of patients on an antiarrhythmic medication discontinued that medication within 1 year. Unfortunately, the reason for discontinuation in our analysis is not known. These data are consistent with discontinuation rates from amiodarone trials
ranging from 27% over a median of 3.8 years to 39% over 1.8 years.24e26 In the optimal pharmacological therapy in cardioverter defibrillator patients (OPTIC) trial, the discontinuation rates of amiodarone and sotalol were high even during the first year: 18% and 24%, respectively.8 Although this analysis represents a large, national cohort of patients from Medicare Part D claims data, several limitations need to be acknowledged. One of the major advantages of claims data is that it reflects an unselected patient population, but inaccurate coding or undercoding could affect the results. In this analysis, it was unknown whether the antiarrhythmic medication was specifically prescribed for VT, but patients with atrial fibrillation or supraventricular tachycardia were excluded. Even within this more narrowly defined patient population, the ICD-9 code for VT does not differentiate nonsustained VT from sustained VT. The indication for ICD implantation (primary vs secondary prevention) was not available. Therefore, the appropriateness of antiarrhythmic drug use was not known. The data presented in the present study were for medication fills, and they may not be representative of provider prescribing patterns. The findings in this older population may not be generalizable to a younger patient population. Although our analysis showed that the clinical characteristics are similar for patients with VT and an ICD enrolled in and not enrolled in Medicare Part D, we were not able to verify the antiarrhythmic medication use of non-Medicare Part D patients. Finally, no outcomes data were presented, as these analyses would be confounded in this Medicare claims-based dataset. Although antiarrhythmic medication and beta-blocker use in patients with VT increased over time, <1 in 4 patients were on an antiarrhythmic medication and only 65% of patients were on a beta blocker. Among those patients on an antiarrhythmic medication, nearly 1 in 3 patients had discontinued the medication at 1 year.
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Disclosures Dr. Pokorney received grants or research support from AstraZeneca, London, United Kingdom, Gilead Sciences, Foster City, California, and Boston Scientific, Marlborough, Massachusetts, and received honoraria for consulting from Medtronic, Dublin, Republic of Ireland and Boston Scientific. All other authors have no conflicts of interest to disclose.
12.
13.
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