Download Economic Evaluation of the HF-ACTION (Heart Failure: A Controlled

Economic Evaluation of the HF-ACTION (Heart Failure:
A Controlled Trial Investigating Outcomes of Exercise
Training) Randomized Controlled Trial
An Exercise Training Study of Patients With Chronic Heart Failure
Shelby D. Reed, PhD; David J. Whellan, MD, MHS; Yanhong Li, MD, MS; Joëlle Y. Friedman, MPA;
Stephen J. Ellis, PhD; Ileana L. Piña, MD; Sharon J. Settles, MS; Linda Davidson-Ray, MA;
Johanna L. Johnson, MS; Lawton S. Cooper, MD, MPH; Christopher M. O’Connor, MD;
Kevin A. Schulman, MD; for the HF-ACTION Investigators*
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Background—Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) assigned
2331 outpatients with medically stable heart failure to exercise training or usual care. We compared medical resource
use and costs incurred by these patients during follow-up.
Methods and Results—Extensive data on medical resource use and hospital bills were collected throughout the trial for
estimates of direct medical costs. Intervention costs were estimated using patient-level trial data, administrative records, and
published unit costs. Mean follow-up was 2.5 years. There were 2297 hospitalizations in the exercise group and 2332 in the
usual care group (P⫽0.92). The mean number of inpatient days was 13.6 (standard deviation [SD], 27.0) in the exercise group
and 15.0 (SD, 31.4) in the usual care group (P⫽0.23). Other measures of resource use were similar between groups, except
for trends indicating that fewer patients in the exercise group underwent high-cost inpatient procedures. Total direct medical
costs per participant were an estimated $50 857 (SD, $81 488) in the exercise group and $56 177 (SD, $92 749) in the usual
care group (95% confidence interval for the difference, $⫺12 755 to $1547; P⫽0.10). The direct cost of exercise training was
an estimated $1006 (SD, $337). Patient time costs were an estimated $5018 (SD, $4600).
Conclusions—The cost of exercise training was relatively low for the health care system, but patients incurred significant
time costs. In this economic evaluation, there was little systematic benefit in terms of overall medical resource use with
this intervention.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.
(Circ Cardiovasc Qual Outcomes. 2010;3:374-381.)
Key Words: costs and cost analysis 䡲 exercise therapy 䡲 heart failure 䡲 cost-benefit analysis
M
Heart Failure: A Controlled Trial Investigating Outcomes
of Exercise Training (HF-ACTION) was a multicenter study
of exercise training plus usual care versus usual care alone in
medically stable outpatients with heart failure and reduced
ejection fraction. The trial randomly assigned 1159 patients to
36 supervised sessions of exercise training followed by homebased exercise, in addition to usual care, and 1172 patients to
usual care alone. In the first 3 months, the exercise training
group had statistically significant but modest improvements in
walk distance, exercise time, peak oxygen consumption, and
self-reported health status.4 During a mean follow-up of 2.5
ore than 4 million Medicare beneficiaries have a
diagnosis of heart failure.1 After hospitalization for
heart failure, approximately 1 in 4 patients are readmitted
within 30 days and two thirds are readmitted within 1 year.1
Postdischarge mortality rate is 10% at 30 days, 22% at 1 year,
and 42% at 5 years.2 In 2009, total direct costs of heart failure
in the United States will be an estimated $33.7 billion, of
which approximately 60% will be attributable to inpatient
care.3 Lower-cost interventions that improve outcomes and
quality of life among patients with heart failure could help to
mitigate the upward trend in health care expenditures.
Received September 4, 2009; accepted May 11, 2010.
The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart,
Lung, and Blood Institute, the National Institute on Aging, or the National Institutes of Health.
From the Duke Clinical Research Institute (S.D.R., D.J.W., Y.L., J.Y.F., S.J.E., S.J.S., L.D.-R., C.M.O., K.A.S.) and Department of Medicine (S.D.R.,
D.J.W., J.L.J., C.M.O., K.A.S.), Duke University School of Medicine, Durham, NC; the Department of Medicine, Jefferson Medical College, Thomas
Jefferson University, Philadelphia, Pa (D.J.W.); the Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio
(I.L.P.); and the Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, Md (L.S.C.).
*The HF-ACTION Investigators are listed in the Data Supplement.
The online-only Data Supplement is available at http://circoutcomes.ahajournals.org/cgi/content/full/CIRCOUTCOMES.109.907287/DC1.
Correspondence to Shelby D. Reed, PhD, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715. E-mail [email protected]
© 2010 American Heart Association, Inc.
Circ Cardiovasc Qual Outcomes is available at http://circoutcomes.ahajournals.org
374
DOI: 10.1161/CIRCOUTCOMES.109.907287
Reed et al
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years, 65% of patients in the exercise training group and 68% in
the usual care group died or were hospitalized for any reason.5
After adjustment for highly prognostic baseline characteristics,
exercise training was associated with modest significant reductions in all-cause mortality or all-cause hospitalization and
cardiovascular mortality or heart failure hospitalization. Exercise
training had nonsignificant effects on cardiovascular mortality or
cardiovascular hospitalization.
Although the clinical benefits of exercise training in HFACTION were modest, the hazard ratios represented the timing
of first events and did not fully reflect the experiences of patients
over time. Furthermore, the exercise regimen required a cost
commitment by health care payers and a time commitment by
patients. Because health care resources and patients’ time are
limited, a wise investment is one in which the value of benefits
realized with an intervention is commensurate with or exceeds
the time and resources required. A secondary objective of
HF-ACTION was to test the hypothesis that exercise training
would be economically attractive (ie, cost-saving or a reasonable
value). Therefore, we estimated the costs of exercise training and
the cumulative medical resource use and costs incurred by
patients enrolled in HF-ACTION from the societal perspective.
We also calculated the cost-effectiveness of exercise training
observed during the trial.
WHAT IS KNOWN
●
Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) is the
largest multicenter randomized trial of exercise training in patients with New York Heart Association
class II to IV heart failure.
●
The trial demonstrated that exercise training, consisting of a program of 36 supervised sessions followed
by home training, conferred improvements in selfreported health status and modest clinical benefits,
based on statistically adjusted, time-to-first-event
analyses, compared with standard care.
WHAT THE STUDY ADDS
●
●
●
Patients with symptomatic heart failure randomly
assigned to exercise training had similar rates of
hospitalizations, emergency department visits, and
urgent care visits compared with patients randomly
assigned to usual care.
Exercise training incurred an additional cost of
approximately $1000 per patient, inclusive of costs
for home exercise equipment.
Patient time costs were also substantial, including
approximately $1000 per patient for time spent on
supervised exercise training and $4000 per patient
for time spent on home exercise.
Methods
The design of HF-ACTION has been described previously.6 Eligible
patients had left ventricular ejection fraction (LVEF) of ⱕ35% and
New York Heart Association class II to IV symptoms. Patients were
Economic Evaluation of HF-ACTION
375
randomly assigned to either exercise training plus usual care or usual
care alone, and both groups received approximately 30 minutes of
education from a nurse and printed materials to promote selfmanagement of heart failure, including a recommendation of 30
minutes of moderate-intensity activity on most days of the week.7
Exercise Training
Patients in the exercise training group were prescribed a regimen of 36
supervised exercise training sessions with a goal of 3 sessions per week
over 12 weeks. After the first 18 sessions, patients were to begin
transition to home-based exercise with a goal of 5 sessions per week.
Home exercise equipment (ie, heart rate monitor and either stationary
bicycle or treadmill) was provided to patients in the exercise training
group. During supervised training, the duration of time spent exercising
was recorded, exclusive of warm-up and cool-down.
Data Collection
Patients in both groups were scheduled for study visits every 3 months
for the first 24 months, then once every 12 months thereafter, with a
maximum follow-up of 4 years. At the 3-month, 12-month, and
24-month visits, patients were to undergo cardiopulmonary exercise
testing and a 6-minute walk test, the latter of which was also to be
performed at the 36-month and final visits. Patients in both groups were
also to receive “monitoring” telephone calls every 2 weeks for the first
9 months, then monthly until 24 months, and quarterly calls thereafter.
Time spent on home exercise by patients in the exercise training group
was to be recorded in adherence logs completed quarterly through 24
months, then at the 36-month and final visits.
The EQ-5D, a 5-item questionnaire used to obtain utility weights
for use in cost-effectiveness analysis, was completed by patients
quarterly through the first year of follow-up, then annually and at the
final visit.8 In addition, detailed information on medical resource use
was collected from patients and verified through available sources.
These resources included 27 types of medication, urgent and nonurgent outpatient visits and procedures, days of home intravenous
therapy, days in skilled nursing facilities and rehabilitation centers,
and inpatient care, including admission and discharge dates, reason
for admission, cardiac procedures, and discharge destination. For
patients enrolled at US sites, hospital billing data were collected for
inpatient admissions and urgent care provided in emergency departments and observation units.
A time survey was developed to obtain estimates of patient travel
time and the time exercise trainers (eg, exercise physiologists,
nurses) spent before and after each session on activities with patients
(eg, scheduling, warm-up) and without patients (eg, cleaning equipment, documentation) from 9 sites. These sites were also asked to
report the number of patients supervised during each training
session. Patients also reported the number of miles they lived from
the exercise facility.
The institutional review board of the Duke University Health
System approved this study. All patients provided written informed
consent.
Cost Estimation of Medical Resources
In accordance with standard methods for economic evaluation in
health care,9 we valued costs from the societal perspective and
reported costs in 2008 US dollars. We discounted costs incurred
beyond the first year of follow-up at 3% per annum. Professional
fees for inpatient services, outpatient visits, and inpatient and
outpatient procedures were based on the 2008 Medicare Physician
Fee Schedule. Medication costs were based on average wholesale
prices and estimated duration of treatment.10 Costs for skilled
nursing and rehabilitative care were based on Medicare reimbursement rates.11,12 Costs for home intravenous therapy were derived
from drug costs11 and government reimbursement rates.11,13
We converted hospital charges to costs by multiplying
department-level cost-to-charge ratios from each hospital’s annual
Medicare cost report and department-specific charges. We applied
the same method to estimate costs of care in emergency departments
376
Circ Cardiovasc Qual Outcomes
Table 1.
July 2010
Counts of Inpatient Tests and Procedures
estimate. For each additional day beyond the median, we applied the
daily cost for a heart failure admission ($1202).
No. (%)
Protocol-Driven Costs
Test or Procedure
Usual Care
(n⫽1172)
Exercise
Training
(n⫽1159)
P
Value*
Cardiac catheterization
171 (14.6)
153 (13.2)
0.33
15 (1.3)
9 (0.8)
0.23
5 (0.4)
6 (0.5)
0.75
PCI with non–drug-coated stent†
10 (0.9)
16 (1.4)
0.22
PCI with drug-coated stent†
26 (2.2)
31 (2.7)
0.48
Heart transplantation
34 (2.9)
22 (1.9)
0.11
8 (0.7)
3 (0.3)
0.14
Coronary artery bypass surgery
PCI without stent†
We also assigned costs to educational resources, tests, procedures,
and study visits required by the protocol. Although both study groups
incurred these costs, we included them in the analysis to better reflect
the total costs required to achieve the levels of adherence and
monitoring observed in HF-ACTION.
Exercise Training
128 (10.9)
85 (7.3)
Combination ICD/pacemaker†
66 (5.6)
66 (5.7)
0.95
From the perspective of the health care system, direct costs for
supervised exercise training include personnel and fixed facility
costs. Direct costs for home-based exercise include equipment costs
and the costs of personnel for “monitoring” calls (assumed to last 15
minutes) to promote adherence. The Appendix shows the unit costs
and assumptions we applied in the cost calculations. The time
exercise trainers spent on each session represents the time before and
after each session plus the time each patient spent exercising.
We conducted sensitivity analyses of the impact of study assumptions on the direct costs of supervised exercise training. First, instead
of the salary of an exercise physiologist, we applied the salary of a
registered nurse. Second, we used a “top-down” cost-estimation
approach in which we assigned the average 2008 reimbursement rate
for cardiac rehabilitation ($36.21) to each exercise session instead of
our cost estimate.14 Finally, we varied the number of patients
simultaneously supervised by one trainer and the fixed cost applied
to each session.
Pacemaker†
12 (1.0)
8 (0.7)
0.38
Patient Time
Biventricular pacemaker or cardiac
resynchronization therapy†
55 (4.7)
57 (4.9)
0.80
Programmed electrophysiology test
45 (3.8)
39 (3.4)
0.54
486 (41.5)
475 (41.0)
0.81
3 (0.3)
7 (0.6)
0.20
Recommendations for economic evaluations in health care also call
for estimation of patients’ time-related costs.9,15 For supervised
exercise sessions, these costs included travel time, time with the
trainer before and after exercise, and time spent exercising; the latter
component varied across sessions and patients. For home exercise,
time was limited to the reported time spent exercising.
293 (25.0)
279 (24.1)
0.60
Transesophageal echocardiogram
43 (3.7)
35 (3.0)
0.38
Cardiac exercise stress test with
imaging
21 (1.8)
22 (1.9)
0.85
Cardiac exercise stress test without
imaging
11 (0.9)
3 (0.3)
0.03
Cardiac pharmacological stress test
with imaging
54 (4.6)
49 (4.2)
0.66
Cardiac pharmacological stress test
without imaging
2 (0.2)
4 (0.3)
0.41
44 (3.8)
42 (3.6)
0.87
9 (0.8)
5 (0.4)
0.29
31 (2.6)
34 (2.9)
0.67
Valve surgery
Intra-aortic balloon pump placement
Left ventricular assist device
placement or removal
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Thoracentesis
6 (0.5)
9 (0.8)
0.42
23 (2.0)
14 (1.2)
0.14
4 (0.3)
5 (0.4)
0.73
Pulmonary artery catheter placement
(eg, Swan-Ganz catheter)
41 (3.5)
41 (3.5)
0.96
Venous catheter placement (eg,
Hickman line)
18 (1.5)
24 (2.1)
0.33
0.003
ICD placement or removal†
ECG
Multigated acquisition scan, rest
Transthoracic echocardiogram
ICD firing
MRI scan, cardiac
Computed tomography scan, cardiac
PCI indicates percutaneous coronary intervention; ICD, implantable
cardioverter-defibrillator; ECG, electrocardiogram; and MRI, magnetic resonance imaging.
*P values were not adjusted for multiple comparisons.
†Procedure characterized by high costs and short length of stay.
and observation units. When bills for these visits were not available,
we applied median cost estimates from available bills.
To impute costs for the 815 (17.6%) hospitalizations for which
complete hospital bills were not available, we multiplied the median
daily costs from available bills for 47 categories representing the
primary reason for admission by the length of stay. To avoid
overestimating costs when patients were hospitalized for procedures
characterized by high costs and short lengths of stay (see Table 1),
we modified this method. When the length of stay for an individual
admission was longer than the median length of stay associated with
the procedure, we estimated costs by assigning the median cost
Cost-Effectiveness Analysis
We estimated the cost-effectiveness of exercise training by calculating the ratio of the difference in mean costs between the exercise
training and usual care groups to the difference in mean qualityadjusted life-years (QALYs).9 To estimate QALYs, we used utility
weights from the United States16 derived from the EQ-5D from
baseline through the final visit to calculate the area under the
quality-adjusted survival curve using the trapezoidal rule. For patients who died, we extrapolated the most recent EQ-5D score to zero
on the death date. In other cases with missing data, we applied the
patient’s most recent utility score.
Statistical Analysis
We used ␹2 tests to compare proportions. Using generalized estimating equations, we compared counts of medical resource use by
applying log links and negative binomial distributions and we
compared costs by applying log links and gamma distributions. In
adjusted comparisons of total costs, we included the 5 prognostic
variables included in the adjusted analyses of the clinical end points5
(ie, duration of cardiopulmonary exercise testing, LVEF, Beck
Depression Inventory II score, history of atrial fibrillation or flutter,
and heart failure etiology) plus the number of hospitalizations during
the 6-month period before random assignment. We used nonparametric bootstrapping to calculate bias-adjusted 95% confidence
intervals (CIs) for differences in costs and QALYs and their joint
distributions.17 We used SAS version 9.1 (SAS Institute Inc, Cary,
NC) for all statistical analyses.
Results
From April 2003 through February 2007, 2331 patients were
enrolled at 82 sites in the United States (n⫽2068), Canada
(n⫽188), and France (n⫽75). Median age at baseline was 59
Reed et al
Table 2.
Total Number of Hospitalizations
3000
Economic Evaluation of HF-ACTION
Medical Resource Use
All-cause: Exercise Training Group
HF-related: Exercise Training Group
All-cause: Usual Care Group
HF-related: Usual Care Group
2500
Mean (SD)
2000
1500
1000
Resource
Usual Care
(n⫽1172)
Exercise
Training
(n⫽1159)
P
Value*
Urgent care visit
1.92 (3.30)
1.83 (2.60)
0.31
Emergency department or
observation unit
1.54 (2.83)
1.46 (2.24)
0.37
Heart failure clinic or office
0.26 (1.11)
0.23 (0.90)
0.37
Stand-alone urgent care facility
500
Outpatient cardiac or orthopedic
procedure
0
0
1
2
377
3
4
Years to Hospitalizations
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Figure 1. Cumulative counts of all-cause and heart failure
hospitalizations.
years, 28% were women, and 40% were racial/ethnic minorities. Median follow-up was 2.5 years in both groups.
Resource Use
A total of 4629 hospitalizations occurred during the
follow-up period: 2297 in the exercise training group and
2332 in the usual care group (P⫽0.92). Figure 1 shows the
cumulative number of all-cause and heart failure hospitalizations. The mean number of inpatient days was 13.6 (standard
deviation [SD], 27.0) in the exercise training group and 15.0
(SD, 31.4) in the usual care group (P⫽0.23).
Table 1 shows the proportions of patients who underwent
inpatient cardiac procedures. Significantly fewer patients in
the exercise training group received an implantable cardioverterdefibrillator (ICD), pacemaker, combination ICD/pacemaker,
biventricular pacemaker, or cardiac resynchronization therapy
(P⫽0.03). However, among patients who received an ICD,
pacemaker or biventricular pacemaker before or during the
study, the proportions were similar (P⫽0.73). Fewer patients
in the exercise group underwent heart transplantation or
placement of a left ventricular assist device (LVAD).
Table 2 shows the mean number of urgent and nonurgent
care visits during follow-up. Urgent care visits were similar
between groups. Patients in the exercise training group had
significantly more nonurgent care visits to specialists other
than cardiologists or orthopedic surgeons and to primary care
physicians, compared with patients in the usual care group.
Other medical resource use was similar between the groups
on average but varied considerably across patients.
Direct Medical Costs
Table 3 shows that mean direct medical costs, excluding the
cost of exercise training, were $5320 lower in the exercise
group compared with the usual care group (95% CI for the
difference, $⫺12 755 to $1547; P⫽0.10). This difference was
attributable to lower mean costs for inpatient care. Although
relatively few patients underwent high-cost inpatient procedures,
median inpatient costs were $2720 lower in the exercise training
group than in the usual care group (95% CI for the difference,
$⫺5551 to $2).
Nonurgent outpatient visit
0.12 (0.44)
0.14 (0.58)
0.15
4.17 (4.15)
4.48 (4.17)
0.02
29.45 (33.62)
31.69 (31.62)
0.01
Cardiologist
7.26 (7.69)
7.46 (7.66)
0.48
Orthopedic surgeon
0.44 (1.48)
0.50 (1.49)
0.40
Other specialist
4.91 (7.59)
5.70 (8.42)
0.01
Primary care physician
6.54 (8.21)
7.26 (7.96)
0.01
Physician extender
1.83 (4.44)
2.23 (6.23)
0.01
Occupational or physical
therapy
1.81 (7.58)
2.02 (7.87)
0.39
Mental health provider
0.88 (6.11)
0.79 (8.04)
0.73
Nurse
3.63 (12.26)
3.82 (11.01)
0.67
Other
2.13 (8.19)
1.91 (6.30)
0.36
Home intravenous therapy, d
4.10 (29.51)
4.94 (27.65)
0.51
Skilled nursing facility, d
1.99 (19.08)
1.64 (12.77)
0.53
Rehabilitation center, d
1.48 (15.15)
0.85 (6.56)
0.15
*P values are from generalized estimating equations regression with
binomial distributions. Estimates represent the mean No. of visits or days per
patient during the follow-up period. P values were not adjusted for multiple
comparisons.
Exercise Training Costs
In 1104 responses to the 9-site time survey, the mean number
of patients supervised during each training session was 1.7
(SD, 1.0). Trainers reported spending a total of 35 minutes on
nonexercise activities for each session, representing the sum
of 4 median estimates of time before and after each session
with and without patients.
On average, patients completed 32.7 (SD, 12.7) supervised
exercise sessions representing 17.1 (SD, 7.9) hours of exercise. When including time before and after each session,
exercise trainers spent an average of 36.0 (SD, 14.8) hours
per patient (assuming a 1:1 patient-to-trainer ratio) and
patients spent an average of 52.8 (SD, 21.2) hours including
travel time. In the base-case analysis with a patient-to-trainer
ratio of 1.7 and the salary of an exercise physiologist, the
direct total cost of supervised exercise training was an
estimated $632 per patient ($588 for personnel and $44 for
facility costs). Mean patient time costs for supervised exercise training were an estimated $1045 per patient.
Figure 2 shows the results of the sensitivity analyses. Costs
decreased as the patient-to-trainer ratio increased, but the relationship was not linear because facility costs remained constant.
At a ratio of 1.7, the estimated cost with a nurse’s salary ($1009)
was closer to the cost derived from the top-down method of
$1183 (SD, $457) per patient. When hourly fixed facility costs
378
Circ Cardiovasc Qual Outcomes
Table 3.
July 2010
Estimated Medical Costs, Intervention Costs, and Patient Time Costs
Usual Care
(n⫽1172)
Cost Component
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Baseline costs, $
Patient education
Cardiopulmonary exercise test
6-Minute walk test
Echocardiogram
Study visit
Protocol costs after baseline, mean (SD), $
Study visits
Cardiopulmonary exercise tests at 3, 12, and 24 mo
6-Minute walk tests at 3, 12, 24, and 36 mo
Monitoring telephone calls*
Total nonintervention protocol costs, including baseline
Medical resources
Concomitant medications
Nonurgent outpatient visits
Outpatient cardiac and orthopedic procedures
Urgent/emergent care visits
Intravenous infusion
Skilled nursing facility
Rehabilitation
Hospitalizations
Inpatient hospital costs
Physician rounding fees
Physician procedure fees
Total, mean
Total, median (interquartile range)
Total direct medical costs
Mean (SD)
Median (interquartile range)
Exercise intervention costs, $
Direct medical costs
Supervised exercise training*
Home exercise training†
Total‡
Patient time
Supervised exercise training
Home exercise training
Total§
Direct nonmedical costs
Travel and parking
Total exercise intervention costs
Total costs, excluding patient time and direct nonmedical costs, $
Mean (SD)
Median (interquartile range)
Total costs, including patient time and direct nonmedical costs, $
Mean (SD)
Median (interquartile range)
Exercise Training
(n⫽1159)
25 (0)
105 (0)
59 (0)
212 (0)
91 (0)
26 (0)
105 (0)
59 (0)
212 (0)
91 (0)
625 (244)
229 (96)
201 (69)
225 (59)
1769 (449)
647 (221)
242 (83)
208 (63)
227 (54)
1817 (401)
8869 (5730)
2196 (2650)
1761 (4769)
1622 (4046)
422 (3007)
565 (5673)
514 (5302)
8847 (5627)
2349 (2382)
1729 (4400)
1400 (2996)
508 (2830)
501 (3928)
299 (2290)
36 308 (83 935)
1491 (2901)
659 (1310)
38 459 (87 432)
10 528 (0–41 706)
31 511 (73 892)
1367 (2570)
529 (1120)
33 407 (76 854)
7807 (0–37 137)
56 177 (92 749)
28 245 (13 067–60 942)
50 857 (81 488)
25 904 (13 574–56 725)
0
0
0
632 (259)
374 (120)
1006 (337)
0
0
0
1045 (418)
3974 (4395)
5018 (4600)
0
0
457 (176)
6482 (4884)
56 177 (92 749)
28 245 (13 067–60 942)
51 863 (81 469)
26 933 (14 470–57 875)
56 177 (92 749)
28 245 (13 067–60 942)
57 338 (81 343)
34 228 (19 840–64 493)
Values are expressed as mean (SD) unless otherwise indicated.
*Based on the salary of an exercise physiologist ($27.83 per hour).
†Includes cost for bike or treadmill, heart rate monitor, shipping, and set-up.
‡Does not include $227 for telephone calls to promote adherence.
§Does not include patient time for telephone calls to promote adherence.
Reed et al
Economic Evaluation of HF-ACTION
379
Figure 2. Direct costs for supervised
exercise training for various patient-totrainer ratios.
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increased by $1.22 per patient, the mean cost of supervised
exercise increased linearly by approximately $43.
Eighty-six percent (997/1159) of patients in the exercise
training group provided exercise logs indicating some home
exercise. Patients spent a mean of 204.7 (SD, 228.0) hours on
home exercise and a median 125.7 hours. Direct costs to
facilitate home exercise training averaged $601, including
$374 in exercise equipment costs and $227 in personnel costs
to promote adherence. Patient time costs for home exercise
were an estimated $3974 per patient.
Total Costs
Total costs in the exercise training group, including direct
medical costs and intervention costs, were an estimated $51 863,
approximately $4300 lower than in the usual care group (95% CI
for the difference, $⫺11 690 to $2631; P⫽0.19). Adjustment for
baseline differences in prognostic variables and previous hospitalizations narrowed the difference in expected total costs be-
tween groups to $2636 ($52 917 in the exercise training group
and $55 553 in the usual care group; P⫽0.43). With the
inclusion of patient time costs and out-of-pocket costs for travel
and parking, total costs in the exercise training group increased
to $57 338, $1161 higher than the usual care group (95% CI for
the difference, $⫺6205 to $8404; P⫽0.73 without adjustment;
P⫽0.36 with adjustment).
Cost-Effectiveness
Among patients who completed the EQ-5D at baseline, mean
undiscounted QALYs were an estimated 2.02 (SD, 1.00)
among 1150 patients in the exercise training group, compared
with 1.99 (SD, 1.01) among 1158 patients in the usual care
group (95% CI for the difference, ⫺0.06 to 0.11). Figure 3
shows a scatterplot of 1000 bootstrap samples representing
the joint distribution of differences in mean direct medical
costs (including intervention costs, excluding patient time,
parking, and travel costs) and mean QALYs. The figure
Figure 3. Scatterplot of 1000 bootstrap
replications representing incremental
costs (including intervention costs and
excluding patient time, travel, and parking costs) and QALYs.
380
Circ Cardiovasc Qual Outcomes
July 2010
indicates that most estimates were consistent with a decrease
in costs (89.9%) and an increase in QALYs (76.5%) and that
73.2% of the bootstrap replications were either associated
with lower costs and increased QALYs or were associated
with increased QALYs at or below the $50 000 per QALY
threshold (upper right quadrant below the line for $50 000 per
QALY). With a $100 000 per QALY threshold, 74.4% of the
estimates would meet the cost-effectiveness criterion. When
we included patient time, parking, and travel costs, 47.9% of
the estimates were at or below the $50 000 per QALY
threshold and 59.2% of the estimates were at or below the
$100 000 per QALY threshold.
Discussion
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During 2.5 years of follow-up, patients in both study groups
incurred an average of more than $50 000 in direct medical
costs, reflecting the high rates of interaction that patients with
heart failure have with the health care system. More than half
of the costs were attributable to inpatient care, and about one
sixth were attributable to medications. Based on point estimates, mean unadjusted direct medical costs in the exercise
training group were $4300 lower than in the usual care group.
However, with patient time, travel, and parking costs, the cost
difference disappeared and there was no statistically significant difference in costs between the groups.
Unlike the adjusted time-to-event analyses in the clinical
study, which found a modest clinical benefit with exercise
training,5 our examination of the cumulative experience of
patients revealed no significant group differences in rates of
all-cause or heart failure hospitalizations. This finding reflects a different approach to examining clinical outcomes.
Time-to-event analyses account for the benefit of delaying a
first event, whereas cumulative event analyses do not consider the timing of events but account for all events during the
follow-up period. Some trialists recommend routine reporting
of the total number of events and the proportions of patients
with first events and their timing.18 Previous trials of heart
failure therapies have also found more modest effects when
examining all events rather than time-to-event end points.19,20
The estimates of cost and cost-effectiveness were also
influenced by the difference in the number of patients who
underwent high-cost inpatient procedures, particularly heart
transplantations and LVAD and ICD implantations. The
finding that significantly fewer patients in the exercise
training group received an ICD during the study may be
attributable to the larger number of patients in the exercise
training group who had an ICD at baseline (42.3%) compared
with the usual care group (38.2%, P⫽0.05). Also, despite
nonsignificant differences in the proportions of patients who
underwent heart transplantation or LVAD placement, the
high cost of hospitalization for these procedures (approximately $200 000 for heart transplantation and $225 000 for
LVAD placement) accounted for approximately 20% of mean
inpatient costs overall. When we excluded costs for these
hospitalizations, mean inpatient costs were similar between
the groups ($23 060 in the exercise training group and
$23 169 in the usual care group). When we applied these
costs in the cost-effectiveness analysis, the proportion of
bootstrap replications consistent with increased QALYs at or
below the $50 000 per QALY threshold decreased from
approximately 73% in the primary analysis to 57%. Using a
threshold of $100 000 per QALY, the proportion increased to
66%. These findings indicate that the cost-effectiveness of
exercise training is relatively uncertain, given that approximately one third of the bootstrap samples were consistent
with decreased QALYs or costs greater than $100 000 per
QALY. In light of this information, decision makers should
consider whether the lower incidence of high-cost procedures
in the exercise training group would likely reoccur if this trial
were conducted again. Such results could be due to chance,
considering the high number of comparisons performed.
On the one hand, most measures of resource use were
remarkably similar between the groups, indicating that it is
unlikely that systematic benefits of exercise training influenced
resource use for most patients. On the other hand, it is possible
that exercise training attenuated the disease process in patients
with more severe heart failure such that fewer end-stage procedures were necessary. A post hoc analysis revealed that among
patients with baseline cardiopulmonary exercise duration of less
than 10 minutes, patients in the exercise training group were less
likely than patients in the usual care group to undergo heart
transplantation or LVAD placement (2.6% versus 5.0%;
P⫽0.03) and incurred significantly lower direct medical costs
($58 846 versus $70 228; P⫽0.03). Furthermore, despite the
lack of a difference in hospital admissions, median inpatient
costs were $2300 lower in the exercise training group. On
average, hospital stays were 0.7 days shorter in the exercise
training group (7.55 versus 6.86; P⫽0.15).
Many of the tests and procedures required by the study
protocol would not necessarily be required for patients to
undertake an exercise training program. Although there may
be a relationship between protocol fidelity in the trial and the
modest clinical and quality-of-life benefits observed,4,5 clinicians may wish to consider ways to reduce costs associated
with exercise training. For example, trainers could supervise
more patients per exercise session. In our base-case analysis,
we assumed that 1 trainer would oversee a mean of 1.7
patients per session. Although this may have been the case at
the 9 sites that participated in the time survey, the representativeness of this estimate is unclear. If exercise training for
patients with heart failure is integrated into existing cardiovascular rehabilitation programs, a 4:1 patient-to-trainer ratio
may be appropriate, assuming there is no impact on patient
outcomes or adherence. With this ratio, estimated costs for
exercise training would be $293 and $454 per patient when
applying salaries for exercise physiologists and nurses, respectively. Determining the optimal patient-to-trainer ratio to
increase efficiency while maintaining adequate monitoring
and adherence will be a critical factor in evaluations of
exercise training from a payer’s perspective.
HF-ACTION is relatively unique in considering the translation of trial results to clinical practice (ie, efficacy to
effectiveness). Adherence in the trial was suboptimal, with
approximately 30% or more of patients training at or above
the target number of minutes per week,5 despite a number of
support structures in place and patients self-identifying for
participation. Without such support systems, adherence levels
probably would be lower, as would expenses for exercise
Reed et al
training by payers. Another factor that may have influenced
comparisons between treatment groups was a potential crossover effect resulting from patients exercising in the usual care
group. Based on self-reported information collected quarterly
during the first 2 years, between 22% and 28% of patients in
the usual care group consistently reported some level of
physical activity. Thus, it is clear that identifying or allowing
for self-selection of individuals most likely to adhere to
exercise training may be a key determination in its ultimate
value, as exploratory evidence from the study indicates that
adherence may be related to clinical outcomes.
4.
5.
Limitations
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Although we believe the resource use and hospital billing data
collected in this study are among the most comprehensive of any
trial-based economic evaluation in heart failure, resource use
data were only collected annually beyond the 24-month visit.
Participants in HF-ACTION may also not be representative of
the heart failure population as a whole. They were generally
younger, had systolic dysfunction, and self-selected for participation. Finally, the multiple hypothesis tests of resource use and
costs may have increased the probability of false-positive findings. Appropriate interpretation of the data requires consideration of the totality of the evidence presented.
6.
7.
Conclusion
Relative to the overall cost of heart failure to the health care
system, costs associated with exercise training are small.
However, in this economic evaluation, we found little systematic benefit in terms of overall medical resource use with
this intervention.
8.
Acknowledgments
We thank Betsy O’Neal and Ann Burnette, Duke University, for
acquisition of hospital billing data, and Damon Seils, Duke University, for assistance with manuscript preparation. They did not receive
compensation for their assistance apart from their employment at the
institution where the study was conducted.
Sources of Funding
HF-ACTION was funded by grants 5U01HL063747, 5U01HL066461,
5U01HL068973, 5U01HL066501, 5U01HL066482, 5U01HL064250,
5U01HL066494, 5U01HL064257, 5U01HL066497, 5U01HL068980,
5U01HL064265, 5U01HL066491, and 5U01HL064264 from the National Heart, Lung, and Blood Institute and grants R37AG018915 and
P60AG010484 from the National Institute on Aging.
Disclosures
None of the authors reported financial disclosures relevant to the
subject matter of the manuscript. Drs Reed and Schulman have
made available online detailed listings of financial disclosures
(http://www.dcri.duke.edu/research/coi.jsp).
References
1. Curtis LH, Whellan DJ, Hammill BG, Hernandez AF, Anstrom KJ, Shea
AM, Schulman KA. Incidence and prevalence of heart failure in elderly
persons, 1994 –2003. Arch Intern Med. 2008;168:418 – 424.
2. Loehr LR, Rosamond WD, Chang PP, Folsom AR, Chambless LE. Heart
failure incidence and survival (from the Atherosclerosis Risk in Communities study). Am J Cardiol. 2008;101:1016 –1022.
3. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB,
Flegal K, Ford E, Furie K, Go A, Greenlund K, Haase N, Hailpern S, Ho
M, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A,
McDermott M, Meigs J, Mozaffarian D, Nichol G, O’Donnell C, Roger
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
Economic Evaluation of HF-ACTION
381
V, Rosamond W, Sacco R, Sorlie P, Stafford R, Steinberger J, Thom T,
Wasserthiel-Smoller S, Wong N, Wylie-Rosett J, Hong Y; American
Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics: 2009 update: a report from the
American Heart Association Statistics Committee and Stroke Statistics
Subcommittee. Circulation. 2009;119:e21– e181.
Flynn KE, Piña IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ,
Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Miller NH, Schulman
KA, Spertus JA, O’Connor CM, Weinfurt KP. Effects of exercise training
on health status in patients with chronic heart failure: HF-ACTION
randomized controlled trial. JAMA. 2009;301:1451–1459.
O’Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ,
Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Miller
NH, Fleg JL, Schulman KA, McKelvie RS, Zannad F, Piña IL;
HF-ACTION Investigators. Efficacy and safety of exercise training in
patients with chronic heart failure: HF-ACTION randomized controlled
trial. JAMA. 2009;301:1439 –1450.
Whellan DJ, O’Connor CM, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ,
Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS,
Houston-Miller N, Fleg JL, Schulman KA, Piña IL; HF-ACTION Trial
Investigators. Heart failure and a controlled trial investigating outcomes
of exercise training (HF-ACTION): design and rationale. Am Heart J.
2007;153:201–211.
Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats
TG, Jessup M, Konstam MA, Mancini DM, Michl K, Oates JA, Rahko
PS, Silver MA, Stevenson LW, Yancy CW, Antman EM, Smith SC Jr,
Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF,
Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American
College of Cardiology; American Heart Association Task Force on
Practice Guidelines; American College of Chest Physicians; International
Society for Heart and Lung Transplantation; Heart Rhythm Society.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of
Chronic Heart Failure in the Adult: a report of the American College of
Cardiology/American Heart Association Task Force on Practice
Guidelines (Writing Committee to Update the 2001 Guidelines for the
Evaluation and Management of Heart Failure): developed in collaboration
with the American College of Chest Physicians and the International
Society for Heart and Lung Transplantation: endorsed by the Heart
Rhythm Society. Circulation. 2005;112:e154 – e235.
Szende A, Oppe M, Devlin N, eds. EQ-5D Value Sets: Inventory, Comparative Review and User Guide. Vol 2. Dordrecht, The Netherlands:
Springer; 2007.
Gold MR, Siegel JE, Russell LB, Weinstein MC, eds. Cost-Effectiveness
in Health and Medicine. New York, NY: Oxford University Press; 1996.
Red Book. Montvale, NJ: Thomson Healthcare; 2006.
Medicare program; home health prospective payment system refinement
and rate update for calendar year 2008; proposed rule. Fed Reg. 2007;
72:23356 –25481.
Medicare program; prospective payment system and consolidated billing
for skilled nursing facilities. Fed Reg. 2007;72:25526 –25600.
Maryland Medicaid Pharmacy Program. On-Line Billing Instructions for
Compounded Home Intravenous Therapy (HIT) Claims. Available at:
http://www.dhmh.state.md.us/mma/mpap/pdf/IVCompoundBilling
InstructionsApr07.pdf. Accessed December 8, 2008.
Centers for Medicare and Medicaid Services. Outpatient PPS Pricer: III ,
Quarter 2008. Available at: http://www.cms.hhs.gov/PCPricer/08_OPPS.asp.
Accessed February 3, 2009.
Russell LB. Completing costs: patients’ time. Med Care. 2009;7:S89–S93.
US Valuation of the EuroQol EQ-5D Health States. December 2005. Agency
for Healthcare Research and Quality, Rockville, MD. Available at: http://
www.ahrq.gov/rice/EQ5Dproj.htm. Accessed December 16, 2009.
Efron B, Tibshirani RJ. Bootstrap methods for standard errors, confidence
intervals, and other measures of statistical accuracy. Stat Sci. 1986;1:54–77.
Poole-Wilson PA, Kirwan BA, Vokó Z, de Brouwer S, Dunselman PH,
van Dalen FJ, Lubsen J; ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) Investigators. Resource utilization implications of treatment were able to be assessed from appropriately reported clinical trial data. J Clin Epidemiol. 2007;60:727–733.
Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators. A
randomized trial of the angiotensin-receptor blocker valsartan in chronic
heart failure. N Engl J Med. 2001;345:1667–1675.
Reed SD, Friedman JY, Velazquez EJ, Gnanasakthy A, Califf RM,
Schulman KA. Multinational economic evaluation of valsartan in patients
with chronic heart failure: results from the Valsartan Heart Failure Trial
(Val-HeFT). Am Heart J. 2004;148:122–128.
Downloaded from http://circoutcomes.ahajournals.org/ by guest on May 12, 2017
Economic Evaluation of the HF-ACTION (Heart Failure: A Controlled Trial Investigating
Outcomes of Exercise Training) Randomized Controlled Trial: An Exercise Training
Study of Patients With Chronic Heart Failure
Shelby D. Reed, David J. Whellan, Yanhong Li, Joëlle Y. Friedman, Stephen J. Ellis, Ileana L.
Piña, Sharon J. Settles, Linda Davidson-Ray, Johanna L. Johnson, Lawton S. Cooper,
Christopher M. O'Connor, Kevin A. Schulman and for the HF-ACTION Investigators
Circ Cardiovasc Qual Outcomes. 2010;3:374-381; originally published online June 15, 2010;
doi: 10.1161/CIRCOUTCOMES.109.907287
Circulation: Cardiovascular Quality and Outcomes is published by the American Heart Association, 7272
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SUPPLEMENTAL MATERIAL
Appendix A. Unit Costs Used to Estimate Costs for the Exercise Training Intervention
Appendix B. HF-ACTION Investigators
Appendix A. Unit Costs Used to Estimate Costs for the Exercise Training Intervention
Resource
Exercise physiologist
Unit Cost
$27.83 per hour


Nurse
$45.72 per hour


Facility cost (fixed direct)
$1.22 per session




Patient
$19.85 per hour

Home exercise equipment
$200 for stationary
bike; $320 for
treadmill; $100
shipping/set-up; $36 for
heart rate monitor


Assumptions
2008 median annual salary for exercise physiologist
($38,008), obtained by averaging across 5 median pay
scales by years of experience
43.5% for fringe benefits allocated over 1960 hours per
year (40 hours per week; 49 weeks per year)
2008 median annual salary for registered nurse ($62,450)
43.5% for fringe benefits allocated over 1960 hours per
year (40 hours per week; 49 weeks per year)
99-foot area valued at $17 per square foot per year
Precor treadmill model 954i at $4725 (5 years of use)
POLAR FS1 Heart Rate Monitor with Non-coded T31
Chest Transmitter at $60 (1 year of use)
Costs allocated over 1960 hours per year (40 hours per
week; 49 weeks per year)
Average US hourly wage ($19.85), not including fringe
benefits, approximating opportunity cost of time for
retirees
Costs based on HF-ACTION administrative records
representing invoices from ICON (Logan, Utah) and Polar
USA, Inc (New York, New York).
Costs may be lower than retail prices for similar models,
but it is assumed that health care payers could negotiate
discounted prices.
Number of miles reported between patients’ homes and
training facilities.
Source
Payscale.com1
US Bureau of Labor Statistics2
US Bureau of Labor Statistics2,3
Loopnet.com4
Duke Center for Living5
Heart Rate Monitors USA6
US Bureau of Labor Statistics2
HF-ACTION administrative records
US Internal Revenue Service7
$0.545 per mile and $2

for parking for each
supervised session
Abbreviation: HF-ACTION, Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training.
1
Payscale.com. Salary Survey Report for Job: Exercise Physiologist. Available at: http://www.payscale.com/research/US/Job=Exercise_Physiologist/Salary.
Accessed December 1, 2008.
2
US Bureau of Labor Statistics. Employer Costs for Employee Compensation, June 2008. Available at:
http://www.bls.gov.news.release/archives/ecec_09102008.pdf. Accessed December 1, 2008.
3
US Bureau of Labor Statistics. Occupational Employment and Wages, May 2008. Available at: http://www.bls.gov/oes/current/oes291111.htm. Accessed
December 1, 2008.
4
Loopnet.com. Available at: http://www.loopnet.com. Accessed December 2, 2008.
5
Duke Center for Living (personal communication, J.L. Johnson)
6
Heart Rate Monitors USA. Available at: http://heartratemonitorsusa.com/monitors-low.html. Accessed December 2, 2008.
7
IRS Publication 436(2008): Travel, Entertainment, Gift, and Car Expenses. Available at: http://www.irs.gov/pub/irs-pdf/p463.pdf. Accessed October 29, 2009.
Travel and parking
Appendix B. HF-ACTION Investigators
Executive Committee: Christopher M. O’Connor, MD, Kerry L. Lee, PhD, Stephen J.
Ellis, PhD, David S. Rendall, BA, PA-C (Duke University, Durham, North Carolina); David J.
Whellan, MD (Thomas Jefferson University, Philadelphia, Pennsylvania); Ileana L. Piña, MD
(Case Western Reserve University, Cleveland, Ohio); Steven J. Keteyian, PhD (Henry Ford
Hospital, Detroit, Michigan); Lawton S. Cooper, MD, MPH, Robin Boineau, MD, Lawrence J.
Fine, MD, DrPH, Jerome L. Fleg, MD, Eric S. Leifer, PhD (National Heart, Lung, and Blood
Institute, Bethesda, Maryland); Virginia Erickson, RN, PhD (University of California, Los
Angeles); Jonathan G. Howlett, MD (Queen Elizabeth II Health Sciences Centre, Halifax, Nova
Scotia, Canada); Nancy Houston Miller, RN, BSN (Stanford University, Stanford, California);
Debra Isaac, MD (Foothills Hospital, Calgary, Alberta, Canada); Robert McKelvie, MD
(Hamilton Health Sciences, Hamilton, Ontario, Canada); Faiez Zannad, MD, PhD (Université
Henri Poincaré, Nancy, France).
Coordinating Center (Duke Clinical Research Institute, Duke University, Durham, North
Carolina): Sharon Boozer, BA, Patty Connolly, Anthony Doll, BA, Stephen J. Ellis, PhD,
Camille Frazier, MD, MHS, Deb Mark, Michelle McClanahan-Crowder, AA, Marcia Meyer,
RN, BSN, Brenda S. Mickley, BS, David S. Rendall, BA, PA-C, Molly Rich, Hoss Rostami,
BSMSE, Sharon Settles, MS, Kathy Spinella, BBA, Jessica Staib, PhD, Omar Thompson, BA.
Steering Committee (U01 Grant Sites): William Abraham, MD, Danuta Biniakiewicz,
PhD, Joann Homan, RN (Ohio State University, Columbus); Vera Bittner, MD, MSPH, Meredith
Fitz-Gerald, RN, BSN (University of Alabama, Birmingham); Gregory Ewald, MD, Heidi
Craddock, RN, Jean Flanagan, RN, MSN (Washington University, St Louis, Missouri); Gregg
Fonarow, MD, Virginia Erickson, RN, PhD (University of California, Los Angeles); Wilson
Colucci, MD, Nancy Z. Lim, RN, Elena Tokareva, PhD (Boston Medical Center, Boston,
Massachusetts); Rami Alharethi, MD, Ray Hershberger, MD, Deirdre Nauman (Oregon Health
and Science University, Portland); Steven J. Keteyian, PhD, Matthew Saval, MS (Henry Ford
Hospital, Detroit, Michigan); Dalane W. Kitzman, MD, Brittney L. Fray, MS, Brian Moore, MS
(Wake Forest University, Winston-Salem, North Carolina); Ileana L. Piña, MD, Marianne Vest,
MA, BSN (Case Western Reserve University, Cleveland, Ohio); Andrew Smith, MD, Gail Snell,
RN, BSN, CCRC (Emory University, Atlanta, Georgia); Eugene Wolfel, MD, Mona Cantu, RN,
NP (University of Colorado Hospital, Aurora).
Steering Committee (Non-U01 Grant Sites): Kirkwood Adams, MD, Jana Glotzer, RN,
MSN, ACNP, Valerie Johnson, RN, Kate Schumacher (University of North Carolina Hospitals,
Chapel Hill); Gordon Blackburn, PhD, Carrie Geither, RN, Susan Moore, RN, BSN (Cleveland
Clinic Foundation, Cleveland, Ohio); A. Bleakley Chandler Jr, MD, Shanda Browning Vaughn,
RN, Paula J. Easler, RN, CCRC, Debbie Williams (University Hospital, Augusta, Georgia);
Julius M. Gardin, MD, Kelly Dimick, RN, Sharon K. Sklar, LPN, Sherri Teller, RN, CCRP (St
John Hospital and Medical Center, Detroit, Michigan); Jalal K. Ghali, MD, Karen Hale-Stenson,
RN (Louisiana State University Health Sciences Center, Shreveport); Mihai Gheorghiade, MD,
Theresa Strzelczyk, APN, CNS (Northwestern University Medical Center, Chicago, Illinois);
Maryl R. Johnson, MD, Cassondra Vander Ark, RN, MS, CCRC (University of Wisconsin,
Madison); Lee R. Goldberg, MD, MPH, Andrew Kao, MD, Jennifer Dekerlegand, MPT, PhD
(Hospital of the University of Pennsylvania, Philadelphia); William E. Kraus, MD, Johanna
Johnson, MS, Brian D. Duscha, MS (Duke University Medical Center, Durham, North Carolina);
Mandeep R. Mehra, MD, Hector Ventura, MD, Bobbett Harris, RN (Ochsner Clinic Foundation,
New Orleans, Louisiana); Monica Colvin-Adams, MD, Kathy Duderstadt, BSN, Karen Meyer,
RN, BSN, Melissa Steger, RN, CCRC (University of Minnesota Medical Center, Fairview);
Barry Cabuay, MD, Ron M. Oren, MD, Page Scovel, RN, BSN, CCRC (University of Iowa
Hospitals and Clinic, Iowa City); Andrew Kao, MD, Tracey Stevens, MD, Karen Haffey, RN,
BSN, CCRC, Christy Mandacina, Ann Stewart, RN, BSN (Mid America Heart Institute, Kansas
City, Missouri); Ann M. Swank, PhD, CSCS, John Manire, MS (University of Louisville,
Kentucky); Paul D. Thompson, MD, Ludmila Cosio-Lima, PhD, Marie Lagasse, MS (Hartford
Hospital, Hartford, Connecticut); Tehmina Naz, MD, Lynne Wagoner, MD, Susan K. Roll, RN,
BSN (University of Cincinnati, Cincinnati, Ohio); Frank G. Yanowitz, MD, Johnny Walker,
Adam Mueller (LDS Hospital, Salt Lake City, Utah); Peter McCullough, MD, Cathy Coleman,
RN, BSN, CCRC, Kimberly A. Dorrell, Tamika Washington (William Beaumont Hospital,
Royal Oak, Michigan); Eileen Handberg, PhD, James A. Hill, MD, Jacqueline Bakos, RN, Alice
Boyette, Pamela Smith, Cynthia Williams, RN, BSN, MS (University of Florida, Gainesville);
Dalynn Badenhop, PhD, Susan Schroeder; Kelly Walter (Medical University of Ohio, Toledo);
Peter Kokkinos, PhD, Elisse Collins, Lauren Korsak, MS (VA Medical Center, Washington,
DC); Eric Eichhorn, MD, Allison Leonard, RN, BSN, Tina Worley, RN, BSN (Medical City
Dallas Hospital, Dallas, Texas); Gerald Fletcher, MD, Phil Peasley, RN, Pam Oldano, RN (Mayo
Clinic, Jacksonville, Florida); John Kostis, MD, Nora M. Cosgrove, RN, BS (University of
Medicine and Dentistry of New Jersey, New Brunswick); Udho Thadani, MD, Lisa Rogan, RN,
BSN, Michelle Thresher, RN, BSN, John Turner, RN (University of Oklahoma Health Sciences
Center, Oklahoma City); Denise Barnard, MD, Denise Herman, MD, Annette Contasti, RN,
Marcy Sagerian, RN (University of California, San Diego Medical Center); Elizabeth Ofili, MD,
Anekwe Onwuanyi, MD, Sunday Nkemdiche, MD (Morehouse School of Medicine, Atlanta,
Georgia); Howard Eisen, MD, James Fitzpatrick, MD, Joyce Wald, DO, Jennie Wong, RN,
CCRP (Temple University Hospital, Philadelphia, Pennsylvania); Myrvin Ellestad, MD, Leslie
Kern, RN, PhD (Long Beach Memorial Medical Center, Long Beach, California); Ezra A.
Amsterdam, MD, Mary J. Burns, RN (University of California-Davis Medical Center,
Sacramento); Savitri Fedson, MD, Ravi K. Garg, MD, Peggy Bennett, RN, Linda Bond, RN,
MSN (University of Chicago Hospitals, Chicago, Illinois); Leway Chen, MD, MPH, Janice
Schrack, RN, BSN (Strong Memorial Hospital, Rochester, New York); Douglas Pearce, MD,
Linda Bond, MSN, RN, Greg Palevo, Margarett Serfass, RN (Saint Thomas Hospital, Nashville,
Tennessee); Daniel Forman, MD, Maria M. Lopez, Yemi Talabi-Oates, April Williams (Brigham
and Women's Hospital and Boston VA Medical Center, Boston, Massachusetts); David Truitte,
MD, Cindy Baumann, RN, CCRN (Lynchburg General Hospital, Lynchburg, Virginia); Jenny
Adams, PhD, Anne Lawrence, RN (Baylor Hamilton Heart and Vascular Hospital, Dallas,
Texas); Dennis McNamara, MD, Emily Gruendler, RN, BSN, Virginia Schneider (University of
Pittsburgh Medical Center, Pittsburgh, Pennsylvania); Steven Hutchins, MD, Alyce Hartwick,
RN (Heart Clinic Arkansas, Little Rock); Paul Campbell, MD, Michele Esposito (Northeast
Medical Center, Concord, North Carolina); Carol Buchter, MD, Rebecca A. Letterer, RN, BSN
(University of Washington Medical Center, Seattle); Robert Taylor, MD, Cheri Wells, RN, MSN
(University of New Mexico Health Sciences Center, Albuquerque); Bruce Johnson, PhD, Beth
Kaping, RN, Susan Leathes, RN (Mayo Clinic, Rochester, Minnesota); Joseph O’Bryan, MD,
Lynn Langley, RN (Southwest Florida Heart Group, Fort Myers); Edward T. Hastings, MD,
Cassandra Clancy, RN, CCRC (St Luke's Medical Center, Milwaukee, Wisconsin); Neil Agruss,
MD, Christine Lawless, MD, Robin Fortman, MS, APN/CNP, CCRC (Central DuPage Hospital,
Winfield, Illinois); Timothy R. McConnell, PhD, Deb Wantz, MSN, RN, CCNS, CCRC
(Geisinger Medical Center, Danville, Pennsylvania); Mary N. Walsh, MD, Regina Margiotti,
CMS, CCRC (The Care Group, Indianapolis, Indiana); Stuart Russell, MD, Elizabeth Heck, RN,
BSN (Johns Hopkins Hospital, Baltimore, Maryland); Justine Lachmann, MD, Diane Lippman,
RN, Jeannette McLaughlin, RN (St Francis Hospital, Roslyn, New York); Joel Landzberg, MD,
Susan Mathus, RN, BSN (Hackensack University Medical Center, Hackensack, New Jersey);
David W. Cullinane, MD, Wyatt Voyles, MD, Dione Lenz, RN, Scott Kaczkowski, BS, CCRC
(Medical Center of the Rockies Foundation, Loveland, Colorado); Jack L. David, MD, Eve
Gillespie, MD, PhD, Pat Keane-Richmond, RN, CCRC (Glacier View Cardiology, Kalispell,
Montana); Steven K. Krueger, MD, Lori Heiss, RN, BS (Bryan LGH Heart Institute, Lincoln,
Nebraska); Stephen Gottlieb, MD, Nancy Greenberg, RN, BSN, MS (University of Maryland
School of Medicine, Baltimore); Neil Gordon, MD, Emily Parks, BS, Melanie Willoughby, RN,
BSN, CCRN (St Joseph’s/Candler Hospital, Savannah, Georgia); Marvin W. Kronenberg, MD,
Jennie Glenn, RN, Carol Madison, RN (Vanderbilt University Medical Center, Nashville,
Tennessee); Malcolm Arnold, MD, Julie K. Smith, RN (London Health Sciences Centre,
London, Ontario, Canada); Eduardo Azevedo, MD, Glen Drobot, MD, Estrellita Estrella-Holder,
RN, BN, MSA, CCNC (St Boniface General Hospital, Winnipeg, Manitoba, Canada); Jonathan
Howlett, MD, Darlene Cooley-Warnell, Sheila Yarn, RN (Queen Elizabeth II Health Sciences
Centre, Halifax, Nova Scotia, Canada); Debra Isaac, MD, Jane Grant, RN, Kim Lyzun (Foothills
Hospital, Calgary, Alberta, Canada); Marie-Helene LeBlanc, MD, Rachel Vienneau, RN, BSc
(Hôpital Laval, Sainte-Foy, Quebec, Canada); Robert S. McKelvie, MD, Linda Beare, Jill
Hancock, LRN (Hamilton Health Sciences, Hamilton, Ontario, Canada); Gordon Moe, MD,
Delores Golob, RN, BA (St Michael's Hospital, Toronto, Ontario, Canada); Kenneth Melvin,
MD, Anne Cymet, RN, Judith Renton, RN (Toronto General Hospital, Toronto, Ontario,
Canada); Anil Nigam, MD, Julie LaLonge (Montreal Heart Institute, Montreal, Quebec,
Canada); Karim Djaballah, MD (Hôpital Brabois, Vandoeuvre-lès-Nancy, France); Patrick
Aebehard, MD (Centre Cardiologique du Nord, Saint-Denis, France); Marie Christine Iliou, MD
(Hôpital Broussais, Paris, France); Remi Sabatier, MD, Annette Belin, MD (Centre Hospitalier
Universitaire de Caen, France); Alain Cohen-Solal, MD (Hôpital Beaujon, Clichy, France); Luc
Hittinger, MD (Hôpital Henri Mondor, Créteil, France).
Data and Safety Monitoring Board: Bertram Pitt, MD (chair), (University of Michigan,
Ann Arbor); Philip A. Ades, MD (University of Vermont, South Burlington); Lotfy L. Basta,
MD (San Francisco, California); Victor Froelicher, MD (Stanford University and Palo Alto VA
Medical Center, Palo Alto, California); Mary Elizabeth Hamel, MD (Beth Israel Deaconess
Medical Center, Boston, Massachusetts); Barry M. Massie, MD (San Francisco VA Hospital,
San Francisco, California); Lemuel Moyé, MD, PhD (University of Texas Health Science
Center, Houston); Lynda H. Powell, PhD (Rush University, Chicago, Illinois).
Cardiopulmonary Exercise Core Lab: William E. Kraus, MD (director); Johanna
Johnson, MS, Lucy Piner, MS (Duke University, Durham, North Carolina); Daniel Bensimhon,
MD (codirector) (LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina);
Stuart Russell, MD (Johns Hopkins University, Baltimore, Maryland).
Echo Core Lab: Julius M. Gardin, MD (director); Renee L. Bess, BS, RDCS, RVT,
Gerald I. Cohen, MD (St John Hospital and Medical Center, Detroit, Michigan).
Heart Rate Training Core Lab: Steven J. Keteyian, PhD (director); Jonathan K. Ehrman,
PhD (associate director); Clinton A. Brawner, MS (coordinator) (Henry Ford Hospital, Detroit,
Michigan).
Adherence Core Lab: Nancy Houston Miller, RN, BSN (codirector) (Stanford University,
Stanford, California); James A. Blumenthal, PhD (codirector); Krista Barbour, PhD (Duke
University, Durham, North Carolina); Tanya M. Spruill, PhD (Columbia University, New York,
New York); Bess Marcus, PhD (Brown Medical School and Miriam Hospital, Providence,
Rhode Island); Jim Raczynski, MD (University of Arkansas for Medical Sciences, Little Rock).
Biomarker and DNA Core Lab: Kirkwood Adams, MD (University of North Carolina,
Chapel Hill); Mark Donahue, MD, Mike Felker, MD (Duke University, Durham, North
Carolina).
Economics and Quality of Life Group: Kevin A. Schulman, MD, Kevin P. Weinfurt,
PhD, Kathryn E. Flynn, PhD, Shelby Reed, PhD, Ann Burnette, BS, Linda Davidson-Ray, MA,
Joëlle Y. Friedman, MPA, Yanhong Li, MS, Li Lin, MS, Betsy O’Neal, BA (Duke University,
Durham, North Carolina).
Clinical End Point Committee: Michael Zile, MD (chair), Ralph H. Johnson (VA Medical
Center and Medical University of South Carolina, Charleston); Daniel R. Bensimhon, MD
(LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina); Vera Bittner, MD,
MSPH (University of Alabama, Birmingham); Robin Boineau, MD (National Heart, Lung, and
Blood Institute, Bethesda, Maryland); Mark E. Dunlap, MD (Case Western Reserve University,
Cleveland, Ohio); William E. Kraus, MD, Christopher M. O’Connor, MD (Duke University,
Durham, North Carolina); Gordon Moe, MSC, MD, FRCP(C) (St Michael's Hospital, Toronto,
Ontario, Canada); John Wertheimer, MD (Thomas Jefferson University and Drexel University
Medical Residents at Abington Memorial Hospital, Philadelphia, Pennsylvania); David J.
Whellan, MD (Jefferson Medical College, Philadelphia, Pennsylvania).