Abstract
Background
Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is recommended prior to primary prevention implantable cardioverter-defibrillator (ICD) placement. Adherence to this recommendation and associated outcomes are unknown.
Objective
We examined use of GDMT (1 or more prescriptions filled for both a renin-angiotensin inhibitor (RAI) and a heart-failure approved beta blocker [HFBB]) within 90 days prior to primary prevention ICD placement in patients with HFrEF.
Methods
We merged data from the National Cardiovascular Data Registry (NCDR) ICD Registry with a 40% random sample of Medicare administrative data and examined prescription fills for recipients of primary prevention ICD in 2007-2011, analyzing GDMT overall and for each U.S. hospital referral region (HRR). We identified characteristics associated with GDMT, and the association with 1-year mortality.
Results
Among 19,733 patients with HFrEF and primary prevention ICD, 61.1% filled any GDMT prior to implant. Across HRRs, GDMT was applied in 51%-71%. Strongest predictors of any GDMT included absence of chronic renal disease or non-sustained ventricular tachycardia (VT), low-income prescription benefits subsidy, and less recent left ventricular ejection fraction (LVEF) evaluation. Patients receiving GDMT versus those without had lower 1-year mortality after ICD implant ((11.1% vs. 16.2%), even after adjustment for comorbidities, LVEF and functional heart failure class.
Conclusions
Rates of GDMT for HFrEF prior to primary prevention ICD Implantation were low, and failure to achieve GDMT is associated with significantly decreased 1-year survival.
Keywords: heart failure, defibrillator, health services research
Introduction
The benefit of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is well established, but no study has examined GDMT use in the critical period prior to implantable cardioverter-defibrillator (ICD) placement for primary prevention of ventricular arrhythmias (1,2). Professional society guidelines recommend treating patients with GDMT for HFrEF prior to ICD implant based on its beneficial effect on HFrEF in general (3-5). Furthermore, primary prevention ICD trials have expected patients to receive appropriate medical therapy before ICD placement. Adherence to GDMT prior to implant has the potential to improve survival and may improve left ventricular ejection fraction (LVEF) enough that an ICD is no longer indicated (6,7).
To better understand GDMT use prior to ICD receipt in the U.S., we linked data from the National Cardiovascular Data Registry (NCDR) ICD Registry with Medicare administrative data and examined prescription fill patterns in the months prior to ICD implant among this older population. We hypothesized treatment with GDMT would be low, revealing an opportunity to improve pharmacotherapy at a critical time for these patients. We examined predictors of GDMT as well as 1-year mortality among patients who did or did not receive GDMT in the 3 months before ICD receipt.
Methods
Study Population
We identified patients in the NCDR ICD registry from 2007 to 2011 who also appeared in a 40% Medicare random sample denominator file (Master Beneficiary Summary File) and were enrolled in fee-for-service Medicare Parts A (inpatient insurance), B (outpatient insurance) and Part D (prescription insurance) at the time of ICD receipt. We included patients in our study cohort if they met the following criteria based on ICD registry data: diagnosed with heart failure, most recent LVEF 40% or less, ICD indication was primary prevention, and no previous ICD implant. Using the Medicare administrative data we excluded patients: under age 65, living outside the United States, without continuous fee-for-service Parts A, B & D enrollment for 6 months before ICD, with no Part D prescription fill record in the 6 months prior to ICD, and without continuous enrollment in fee-for-service Parts A and B in the 12 months after implant date or until death (Online Table 1).
Outcome
GDMT was defined as 1 or more prescription fill for both a heart failure beta blocker (HFBB), carvedilol, metoprolol, or bisoprolol, and any renin-angiotensin inhibitor (RAI) (angiotensin converting enzyme inhibitor or angiotensin receptor blocker) in the 90 days before ICD implantation (Online Table 2). As a conservative assumption we included both short- and long-acting formulations of beta blockers. The 90-day search time prior to ICD was selected to reflect the minimum recommendation of the Heart Failure Society of America 2006 and 2010 Comprehensive Heart Failure Practice Guideline, which suggests a GDMT trial period of 3 to 6 months before primary prevention ICD (4). Selected medications were identified from the Medicare Part D Prescription Drug Event (PDE) file, which records pharmacy dispensing events. We measured GDMT in 2 ways. First, we identified patients with 1 or more fill of both RAI and HFBB in a 90-day pre-implant period, a measure of the receipt of any GDMT. Second, we assessed receipt of an adequate supply of GDMT defined as a medication possession ratio of at least 80% of days covered by GDMT in a 90-day pre-implant period (i.e. 72 of 90 days). This was achieved by assessing GDMT fills in the 180 day pre-ICD period to permit supply carry over into the 90-day pre-ICD period. We classified each of the 90 pre-implant days as covered or not using the fill date and the days' supply variables. We assumed dispensed medication supply was not used during inpatient stays (e.g. acute care hospitalization or rehabilitation). We used the Medicare denominator file to measure death within one year following ICD implantation.
Covariates
Patient characteristics were identified from ICD registry and Medicare data. The Medicare denominator file was used to identify race and ethnicity, categorized as black, Hispanic or other (8). Low income status was based on receipt of the Medicare Part D low income subsidy dichotomized, a proxy measure of income 150% or less of federal poverty level. The following comorbidities, diagnosed on 1 inpatient or 2 outpatient Medicare claims in the 6 months before ICD implant, were also ascertained: cerebrovascular disease, chronic obstructive lung disease including tobacco use, chronic renal disease, dementia, and diabetes. Number of hospital admissions and admission length in the 6-months prior to ICD receipt were determined from the Medicare Part A claims. Residential ZIP code was used to assign each patient to a Dartmouth Atlas of Health Care Hospital Referral Region (HRR), which represent regional health care markets for tertiary medical care (9). ICD Registry covariates included: ischemic heart disease, non-ischemic dilated cardiomyopathy, past non-sustained ventricular tachycardia, duration of heart failure, New York Heart Association functional class, LVEF and time since last LVEF measurement.
Statistical Models
We used descriptive statistics to assess characteristics of the cohort overall and across sub-groups defined by pre-ICD implant GDMT use. Relative risk coefficients were estimated using a Poisson model in which GDMT receipt was a function of demographics, comorbidities, and heart failure severity. In addition, we used Poisson regression to model the association between receipt of both any or adequate pre-implant GDMT and 1-year mortality adjusted for patient characteristics and heart failure severity. Our final models showed no evidence of over-dispersion. For regional measures of GDMT, we calculated the age, sex and race-adjusted proportion of patients in the 133 regions with 50 or more total primary prevention ICD recipients in our study sample. The Committee for the Protection of Human Subjects at Dartmouth College approved this study.
Results
The random 40% Medicare sample included 172,877 in the ICD registry; of these 78,655 met our inclusion criteria. Exclusions due to requiring continuous Medicare enrollment, age > 65, and restriction to the contiguous United States decreased the cohort from 78,655 to 20,188. Requiring that 1 of any kind of prescription (not just GDMT) had been filled in the prior 6 months further reduced the cohort from 20,173 to 19,773 (Online Table 1). Table 1 shows patient characteristics overall and according to receipt of GDMT. Mean age was 74.9 (Standard Deviation [SD] 6.2) and 35.4% were female. Based on ICD registry data, 74.4% of patients had ischemic heart disease and 62.0% had non-ischemic dilated cardiomyopathy; both conditions were reported for some patients. Symptom severity was moderate with most patients reported to have NYHA class 2 or 3 symptoms. LVEF was 20-30% for 70.6% of patients and below 20% for 12.4% of patients. Heart failure was diagnosed more than 9 months prior to implant for 70.6% of patients and the most recent evaluation of LVEF was within 1 month of implant for 49.0% of patients. Patients were hospitalized on average 1.9 times (SD 1.4) in the 6 months before ICD.
Table 1. Demographic and Clinical Characteristics of Patients Categorized by Guideline Directed Medical Therapy Prior to Implant.
| Total | No GDMT Prescriptions Filled | Any GDMT Prescription Filled | At least 80% days covered by GDMT | |
|---|---|---|---|---|
| N (% total) | 19,773 | 7,700 (38.9%) | 12,073 (61.1%) | 5,590 (28.3%) |
|
| ||||
| Mean age in years (SD) | 74.9 (6.2) | 75.5 (6.3) | 74.5 (6.2) | 74.6 (6.1) |
| Black race (%) | 1,941 (9.8) | 689 (9.0) | 1,252 (10.4) | 503 (9.0) |
| Hispanic ethnicity (%) | 1,359 (6.9) | 477 (6.2) | 882 (7.3) | 347 (6.2) |
| Female (%) | 6,989 (35.4) | 2,477 (32.2) | 4,512 (37.4) | 2,139 (38.3) |
| Medicare prescription low income subsidy (%) | 6,696 (33.9) | 2,376 (30.9) | 4,320 (35.8) | 1,949 (34.9) |
| Mean hospital admissions in 6 months prior to implant (SD) | 1.94 (1.38) | 1.88 (1.36) | 1.98 (1.4) | 1.70 (1.1) |
| Year of Implant (%) | ||||
| 2007 | 2,382 (12.1) | 991 (12.9) | 1,391 (11.5) | 611 (10.9) |
| 2008 | 4,601 (23.3) | 1,787 (23.2) | 2,814 (23.3) | 1,321(23.6) |
| 2009 | 4,634 (23.4) | 1,760 (22.9) | 2,874 (23.8) | 1,271 (22.7) |
| 2010 | 4,281 (21.7) | 1,674 (21.7) | 2,607 (21.6) | 1,211 (21.7) |
| 2011 | 3,875 (19.6) | 1,488 (19.3) | 2,387 (19.8) | 1,176 (21.0) |
| Comorbidities from Medicare Claims(%) | ||||
| Cerebrovascular disease | 4,690 (23.7) | 1,910 (25.8) | 2,780 (23.0) | 1,153 (20.6) |
| Chronic pulmonary disease | 9,016 (45.6) | 3,647 (47.4) | 5,369 (44.5) | 2,293 (41.0) |
| Chronic renal disease | 6,193 (31.3) | 2,713 (35.2) | 3,480 (28.8) | 1,413 (25.3) |
| Dementia | 508 (2.6) | 228 (3.0) | 280 (2.3) | 98 (1.8) |
| Diabetes | 10,010 (50.6) | 3,894 (50.6) | 6,116 (50.7) | 2,755 (49.3) |
| Clinical Data from ICD Registry (%) | ||||
| Ischemic heart disease | 14,689 (74.4) | 5,897 (76.7) | 8,792 (73.0) | 4,039 (72.4) |
| Non-ischemic dilated cardiomyopathy | 12,238 (62.0) | 4,336 (56.4) | 7,902 (65.6) | 3,744 (67.1) |
| Prior non-sustained ventricular tachycardia | 4,553 (23.1) | 2,093 (27.2) | 2,460 (20.4) | 1,017 (18.2) |
| New York Heart Association Class (%) | ||||
| Class 1 | 537 (2.72) | 188 (2.5) | 349 (2.9) | 180 (3.2) |
| Class 2 | 5,796 (29.4) | 2,131 (27.8) | 3,665 (30.4) | 1,835 (32.9) |
| Class 3 | 12,519 (63.5) | 4,963 (64.7) | 7,556 (62.8) | 3,375 (60.6) |
| Class 4 | 857 (4.4) | 388 (5.1) | 469 (3.9) | 183 (3.3) |
| Duration of Diagnosed Heart Failure Prior to Implant (%) | ||||
| < 3 months | 2,684 (13.6) | 1,229 (16.0) | 1,455 (12.1) | 547 (9.8) |
| 3 months - 9 months | 3,104 (15.8) | 1,111 (14.5) | 1,993 (16.6) | 937 (16.8) |
| > 9 months | 13,917 (70.6) | 5,341 (69.5) | 8,576 (71.3) | 4,083 (73.3) |
| Left Ventricular Systolic Function | ||||
| Mean LVEF (SD) | 25.58 (6.6) | 25.69 (6.7) | 25.52 (6.5) | 25.93 (6.3) |
| EF < 20% | 2,432 (12.4) | 967 (12.7) | 1,465 (12.3) | 577 (10.4) |
| EF 20-25% | 8,345 (42.6) | 3,153 (41.4) | 5,192 (43.4) | 2,383 (43.0) |
| EF 26-30% | 5,476 (28.0) | 2,125 (27.9) | 3,351 (28.0) | 1,621 (29.3) |
| EF 31-35% | 2,872 (14.7) | 1,161 (15.3) | 1,711 (14.3) | 863 (15.6) |
| EF 36-40% | 449 (2.3) | 207 (2.7) | 242 (2.0) | 98 (1.8) |
| Timing of Most Recent LVEF Measurement Prior to Implant (%) | ||||
| < 1 month | 9,552 (49.0) | 4,186 (55.2) | 5,366 (45.0) | 2,331 (42.2) |
| 1 month - <3months | 5,409 (28.0) | 1,805 (23.8) | 3,604 (30.2) | 1,655 (30.0) |
| 3 months - <6 months | 2,236 (11.5) | 728 (9.6) | 1,508 (12.7) | 774 (14.0) |
| > 6 months | 2,318 (11.9) | 871 (11.5) | 1,447 (12.1) | 760 (13.8) |
Guideline-directed medical therapy (GDMT) was defined as filling prescription for carvedilol, metoprolol, or bisoprolol and an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in the 90-day pre-implant period. Low income subsidy is a dichotomous indicator of poverty equal to < 150% of the federal poverty level and based on the Medicare Part D low income subsidy qualification variable, dichotomized. LVEF = left ventricular ejection fraction
Overall 12,073 (61.1%) patients received any GDMT in the 90 days prior to ICD receipt while 5,590 (28.3%) received an adequate supply (80% coverage of the 90 days prior to implant) of both a HFBB and a RAI (Table 2). The proportion of patients receiving GDMT was consistent from year to year. Age, sex, race/ethnicity, poverty, and comorbidities were similar among those receiving and not receiving GDMT. At least 1 HFBB or RAI prescription was filled by three-quarters of patients but slightly less than half were dispensed a supply sufficient to cover at least 80% of those 90 days. A sensitivity analysis examining the use of any beta blocker (HF approved or not) showed only slightly higher rates compared with HFBB. The mean number of days covered for HFBB and RAI were 69 and 70, respectively, consistent with a bimodal distribution in which patients had either a high or low number of days covered. Mean days covered by subgroup is shown in Online Table 4.
Table 2. Prescription Fill Rates for Guideline Directed Medical Therapy During 90 Days Prior to ICD Implant.
| Medication Type | Any GDMT Prescription Filled | At least 80% days covered by GDMT |
|---|---|---|
| ACEi or ARB | 74.3% | 46.3% |
| Heart failure beta blocker | 77.1% | 47.0% |
| Any beta blocker | 80.7% | 52.8% |
| ACEi or ARB plus heart failure beta blocker | 61.1% | 28.3% |
| ACEi or ARB plus any beta blocker | 63.7% | 32.0% |
ICD = Implanted Cardioverter-Defibrillator, GDMT = Guideline-directed medical therapy
The strongest predictors of filling any GDMT prescription included absence of chronic renal disease, absence of past non-sustained VT, receipt of a low-income prescription benefits subsidy, and the most recent left ventricular ejection fraction (LVEF) evaluation more than 1 month prior to implant. Table 3 presents Poisson regression results for factors associated with GDMT receipt. LVEF, NYHA functional class, race, diabetes, dementia, and timing of symptom onset were not significantly associated with receipt of GDMT.
Table 3. Poisson Regression Results: Patient characteristics significantly associated with filling one or more prescription for GDMT in the 90 days prior to implant.
| Parameter | RR | 95% CI | p-value |
|---|---|---|---|
| Age | 0.99 | (0.99, 0.99) | < 0.001 |
| Female | 1.06 | (1.02, 1.10) | 0.003 |
| Low Income Subsidy | 1.07 | (1.03, 1.12) | 0.001 |
| COPD/Tobacco | 0.95 | (0.91, 0.98) | 0.004 |
| Chronic Renal Disease | 0.89 | (0.85, 0.93) | < 0.001 |
| No. Hospital Admissions | 1.03 | (1.02, 1.04) | < 0.001 |
| Duration of CHF <3 months | 0.91 | (0.85, 0.96) | 0.001 |
| Non-Ischemic Dilated Cardiomyopathy | 1.07 | (1.01, 1.14) | 0.03 |
| Non-sustained Ventricular Tachycardia | 0.90 | (0.86, 0.94) | < 0.001 |
| Most Recent LVEF >1 month - <3months | 1.16 | (1.11, 1.21) | < 0.001 |
| Most Recent LVEF > 3 months - <6 months | 1.16 | (1.09, 1.23) | < 0.001 |
| Most Recent LVEF >6 months | 1.09 | (1.02, 1.15) | 0.01 |
GDMT = guideline directed medical therapy, defined as filling one or more prescription for carvedilol, metoprolol, or bisoprolol and an ACEI or ARB in the 90-day pre-implant period. COPD = chronic obstructive pulmonary disease. CHF = congestive heart failure. Model covariates also included black race, Hispanic ethnicity, cerebrovascular disease, dementia, diabetes, timing of heart failure symptom onset 3-6 months, ischemic heart disease, NYHA class, left ventricular ejection fraction (LVEF) at most recent assessment. Timing of most recent LVEF is compared with assessment < 1 month prior to implant. Duration of CHF < 3 months is compared with duration > 9 months.
Death within 1 year of implantation occurred less frequently for patients receiving any pre-implant GDMT compared to those receiving none (11.1% vs. 16.2%, respectively). In models adjusting for individual characteristics, comorbidities and heart failure severity, patients who filled any GDMT remained significantly less likely to die within 1 year (adjusted RR 0.80 (95% CI 0.73, 0.87)) (Online Table 5). Death within 1 year after implantation was also less common for patients with adequate GDMT (9.4% vs. 14.6%, adjusted RR 0.80 (95% CI 0.72, 0.89).
We examined geographic variation in the proportion of patients not achieving GDMT across 135 U.S. health referral regions (HRR) with more than 50 ICDs implanted within our study sample. The proportion of patients who filled any GDMT ranged from 44% to 76% (51% to 71% for 5th to 95th percentile). The proportion of patients with an adequate supply was much lower, ranging from 16% to 49% (5th to 95th percentile: 19% to 38%) (Figure 1).
Figure 1. Use of Guideline-Directed Medical Therapy for Heart Failure Prior to ICD Implant for 133 Hospital Referral Regions.
This shows the proportion of patients with HFrEF receiving GDMT prior to implant of a primary prevention ICD for 133 Hospital Referral Regions (HRR) in the United States. Included were HRR in which > 50 ICD were implanted during study sample years 2007-2011. HFrEF = Heart failure with reduced ejection fraction; ICD = Implantable cardioverter-defibrillator
Discussion
Among Medicare beneficiaries with at least moderate HFrEF, we found 61% of patients filled 1 or more prescription for GDMT in the 90 days prior to receiving a primary prevention ICD but only half that many received a supply adequate to cover 80% of those days. In this cohort of older Americans fully insured by Medicare, we also observed broad regional variation in the proportion of patients receiving adequate GDMT prior to ICD receipt, ranging from as low as 16% to 49% across HRRs. These disparities in the use of heart failure pharmacotherapy suggest opportunities to improve the selection and care of patients receiving primary prevention ICD (10).
Our findings reveal the ICD recipients with the shortest duration of heart failure and most recently evaluated LVEF were least likely to receive an adequate trial of medical therapy. This association between use of GDMT and both the timing of heart failure diagnosis and the timing of the measurement of LVEF was independent of comorbidities and heart failure severity, suggesting nonclinical factors may play a role in preventing adequate trials of heart failure pharmacotherapy. For example, receipt of a low-income prescription benefit subsidy available to Medicare beneficiaries with income less than 150% of the Federal poverty level significantly increased the likelihood of filling prescriptions for GDMT.
Why might a physician not prescribe a trial of GDMT prior to ICD implant? A history of non-sustained VT and chronic renal disease were associated with a lower likelihood of filling GDMT prescriptions in our study. The use of electrophysiology testing, severe symptoms during non-sustained VT, persistent hypotension, or chronic kidney disease may lead a physician to forgo treatment with GDMT for the recommended 3 to 6 months prior to ICD implant. However these clinical scenarios are unlikely to explain the wide regional variation in GDMT use observed in our study. For example, prescriptions for adequate GDMT were filled by only 24-29% of ICD recipients in Los Angeles, Houston, and Atlanta, the 3 busiest HRRs in our study sample.
The identification of high-risk subpopulations such as those not receiving pre-implant GDMT is clinically important given the potential survival benefit of heart failure pharmacotherapy for patients with HFrEF in general and the potential to improve selection of patients for primary prevention ICD therapy (10). Current recommendations for selecting ICD candidates rely on the clinical characteristics most likely to improve with adequate GDMT prior to implant, including NYHA functional class and LVEF. In the future, physicians should consider documenting medication prescription fills as evidence of a trial of appropriate GDMT in addition to clinical criteria.
SCD-HeFT (the Sudden Cardiac Death in Heart Failure Trial), the largest randomized clinical trial of primary prevention ICD therapy, enrolled patients receiving GDMT for at least 4 weeks. A recent study found no difference in GDMT prescription rates at discharge following ICD implant, and no difference in survival overall, between patients enrolled in SCD-HeFT and propensity-score matched patients enrolled in the NCDR ICD registry (11,12). While substantial differences exist between our patient populations and those in randomized clinical trials of primary prevention ICD (notably our inclusion of patients with chronic renal disease) the death rate among patients without any pre-implant GDMT at 1 year in our study was twice as high as both the ICD and comparator arms of the SCD-HeFT trial (16.2% in our study vs. 8.8% and 7.7% in SCD-HeFT respectively).
Prior studies have examined gaps in the delivery of GDMT. Miller et al. found that 25.7% of medication-eligible patients failed to receive prescriptions for optimal medical therapy at the time of discharge following ICD implant (13). This low rate of prescribing is particularly concerning because the registry variables explicitly included contraindications to GDMT following implant, something we cannot replicate with the claims data used in our study. Only 1 other study has examined the role of medication use before ICD implantation. Hauptman et al. used prescription claims data and found, in a large managed care organization between the years 2003-2006, the median number of days covered by any HFBB during the 90 days prior to ICD implant was 46. This compares with a median of 81 days and mean of 69 days in our study for HFBB (14). Notably, the cohort for their study was younger (mean age 60) and healthier with lower rates of diabetes and lung disease, and was not nationally representative. The increase in the prescribing of HFBB from the mid-2000s to the more recent cohort in our study is consistent with national trends and reflects successful diffusion of this important therapy. For example, a cohort of patients receiving primary prevention ICDs at 14 academic hospitals between 2006-2009 had discharge prescription rates as high as 91% for HFBB (15).
Adherence to medical therapy is often difficult for implanting physicians to ascertain in routine clinical practice. Increased access to electronic health records linked to pharmacy databases may provide opportunities for physicians to better identify patients not filling prescriptions for GDMT. Information about outpatient medication prescription use and careful medication reconciliation by a patient's managing cardiologist should be a vital component of clinical evaluation of HFrEF patients prior to referral for primary prevention ICD therapy.
Limitations
Our study was a retrospective data analysis and therefore subject to the limitation common to this research. The association between GDMT prior to ICD implantation and 1 year survival should not be assumed causal. Indeed, patients who do not fill prescriptions are known to be different from those that do fill prescriptions; these differences are not always well-accounted for by traditional risk adjustment (16). The survival benefit associated with GDMT receipt before ICD implant may represent the effect of other characteristics correlated with filling prescriptions. Confounding due to these factors could lead to an overestimation of the magnitude of benefit from GDMT. However, given our use of detailed clinical characteristics including NYHA class and LVEF, it is unlikely that this survival benefit is biased by differences in heart failure severity.
Our study uses pharmacy fill records to assess prescription receipt. We cannot know if low rates of GDMT are due to inadequate prescribing by physicians or barriers to patients' filling prescriptions. We cannot know whether managing physicians were aware of their patients' adherence rates. Similarly, we have no data on contraindications to GDMT for our study population. However medication contraindications are not a likely explanation of the observed geographic variation between HRR.
Finally, we defined GDMT as treatment for 90 days prior to ICD receipt however alternate definitions could be considered and might produce different results. A formal evaluation of clinical benefit rather than an arbitrary amount of time may be the best determinant of an adequate GDMT trial prior to ICD.
Conclusions
Rates of GDMT for HFrEF prior to implantation of primary prevention ICDs are low in this Medicare population and failure to achieve GDMT is associated with significantly decreased survival within the first year following ICD implant. There is significant regional variation in the delivery of GDMT during this critical time prior to ICD implant. An adequate trial of GDMT prior to ICD implantation should be part of routine clinical practice. Better delivery of GDMT may improve clinical outcomes and decrease the need for ICD therapy among those patients whose heart failure responds to medical therapy.
Supplementary Material
Online Table 1. Cohort Selection Criteria
Online Table 2. Medications used to define Guideline Directed Medical Therapy
Online Table 3. Full Patient Characteristics
Online Table 4. Mean Days of Guideline Directed Medical Therapy (GDMT) and Medication Possession Ratio of 80%
Online Table 5. Poisson Regression Results: Risk of Death within One Year of Implantable Cardioverter Defibrillator (ICD) Implant associated with Patient Characteristics and Prescription fill
Central Illustration. Medications before defibrillator implantation: Number of U.S. Hospital Referral Regions.
Perspectives.
Competency In Patient Care
When not contraindicated, patients with heart failure and reduced ejection fraction (HFrEF) should receive guideline directed medical therapy prior to implantation of an automatic defibrillator for primary prevention of ventricular arrhythmic death.
Translational Outlook
Further studies are needed to understand the interaction between pharmaceutical and device therapies particularly for elderly patients with HFrEF.
Acknowledgments
GR and NM had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. GR developed the research plan and wrote the initial manuscript. WZ analyzed data. GR, JP, JS, RZ and NM developed the analytic plan and edited the manuscript.
Funding Sources: This research was supported by NIH 01 AG046830 from the National Institute on Aging, “Technology Diffusion, Health Outcomes, and Healthcare Expenditures”; Jon Skinner (PI)
Abbreviations
- GDMT
Guideline-directed medical therapy
- LVEF
Left ventricular ejection fraction
- HFrEF
Heart failure with reduced ejection fraction
- ICD
Impanted cardioverter defibrillator
- HFBB
Heart failure beta blocker
- NCDR
National Cardiovascular Data Registry
- RAI
Renin-angiotensin inhibitor
- SCD-HeFT
Sudden Cardiac Death in Heart Failure Trial
Footnotes
Disclosures: GAR: Grant funding from Medtronic Philanthropy, Consulting Fees from Fujifilm Sonosite; JEP: Consulting fees from Boston Scientific and Physio Control. Honoraria from Boston Scientific, Medtronic, and St. Jude Medical. Equity options in Cameron Health, Inc.; WZ: None; RZ: None. JS: Shareholder in Dorsata, Inc.; NEM: None
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Online Table 1. Cohort Selection Criteria
Online Table 2. Medications used to define Guideline Directed Medical Therapy
Online Table 3. Full Patient Characteristics
Online Table 4. Mean Days of Guideline Directed Medical Therapy (GDMT) and Medication Possession Ratio of 80%
Online Table 5. Poisson Regression Results: Risk of Death within One Year of Implantable Cardioverter Defibrillator (ICD) Implant associated with Patient Characteristics and Prescription fill