MD J Paul Mounsey

PHD Jennifer D Schwartz

CiteSeerX

Journal of the American College of Cardiology Vol. 62, No. 25, 2013
 2013 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00
Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2013.08.719EDITORIAL COMMENT
Why Are Clinically Indicated,
But Lower-Risk, Patients Less
Likely to Receive Implantable
Cardioverter-Defibrillator and
Cardiac Resynchronization
Therapy?*
J. Paul Mounsey, MD, PHD,
Jennifer D. Schwartz, MD
Chapel Hill, North Carolina
High-voltage device therapy is one of cardiology’s great
success stories of the past 20 years. Patients known to be at
risk of sudden deathdprincipally those with left ventricular
systolic dysfunctiondcan be identified in advance of their
arrhythmic events and prophylactic implantable cardioverter-
defibrillator (ICD) therapy initiated. When the patient has
disordered intraventricular conduction, addition of cardiac
resynchronization therapy (CRT) has a further beneficial,
albeit smaller, effect on mortality in addition to the desirable
reduction in heart failure symptoms and heart failure hospi-
talizations that CRT brings. Although the results of major
prospective randomized trials of transvenous ICD and CRT
therapy have all been consistent, implantation of high-voltage
devices in indicated patients is declining.See page 2406Prophylactic high-voltage device implantation began in
1996 with the publication of the first primary prevention trial,
MADIT (Multicenter Automatic Defibrillator Implantation
Trial) (1), and volume grew up to about 2005 (2). The early
CRT trials (COMPANION [Comparison of Medical
Therapy, Pacing, and Defibrillation in Heart Failure] [3]
and MIRACLE [Multicenter InSync Randomized Clinical
Evaluation] [4]) and the subsequent introduction of the idea*Editorials published in the Journal of the American College of Cardiology reflect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Clinical Electrophysiology, Division of Cardiology, Department of
Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Dr. Mounsey has a consultant relationship with Medtronic and has received speaking
honoraria from Medtronic, Boston Scientific, and St. Jude Inc. Dr. Schwartz has
reported that she has no relationships relevant to the contents of this paper to disclose.that CRT could be administered prophylactically (MADIT
CRT [5] and REVERSE [Resynchronization Reverses
Remodeling in Systolic Left Ventricular Dysfunction] [6])
bolstered the growth of high-voltage device implantation.
Since then, however, implantation rates have been declining
such that current rates are down by about one-quarter
compared with their peak period ( Jeffries Group Inc.,
unpublished data, 2013) (CitiGroup Investments, unpub-
lished data, March 23, 2011).
Why are high-voltage device implantation rates so low?
There are many possible reasons. It may be that the number
of appropriate patients is in fact smaller than anticipated
despite a larger pool of patients meeting indications. Recent
technological problems may influence physicians to shy away
from referring indicated patients. In addition, convincing
referring physicians of the clear mortality benefit seems to be
an ongoing challenge.
This last point is addressed in the current article by
Finegold et al. (7) in this issue of the Journal. The authors
reviewed mortality benefit from CRT in 7 major trials
comparing biventricular pacing versus no biventricular
pacing. They used the measurement of life span gained,
which has the advantage of providing a clinical context in
which to relate clinical trial results to individual patients.
Over 24 months of follow-up (the typical length of
a prospective randomized trial), they observed that life span
gained grew at a greater rate over time. The observed life
span gain at 24 months was >4 times greater than that at 12
months. Although it is widely accepted that CRT positively
affects mortality, the authors eloquently demonstrate the
durability of the benefit.
Due to the overwhelming cost, clinical trials are designed
to last as long as necessary to prove or disprove benefit. In the
case of CRT trials, this is approximately 2 years. However,
the life of a CRT device is about 5 years, and many patients
live long enough to receive >1 device. The authors (7)
extrapolated the hazard ratios over the life of a device (i.e.,
5 years), thus enabling them to estimate the life span gained.
Although clearly relying on assumptions, this is a practical
way of looking at longer-term results without prolonging
expensive clinical trials. When the authors reviewed the
life span gained for the compiled trial data at 1, 2, 3, and
5 years after device implantation, it grew over time, and the
number-needed-to-treat (NNT) decreased. In fact, in
COMPANION (3), the NNT was 101.8 at 1 year and
dramatically dropped to 7.4 at 3 years. In CARE-HF
(CArdiac REsynchronization Heart Failure), the NNT was
75.8 and 6.0 at 1 and 3 years, respectively; in RAFT
(Resynchronization-defibrillator Ambulatory Heat failure),
the NNT dropped from 91.3 at 1 year to 4.8 at 5 years.
Even more interesting were the findings of Finegold et al.
(7) when extrapolated to 15 and 20 years. At 5 and 10 years,
there was greater benefit (more life span gained) in the
higher-risk patients. However, lower-risk patients live lon-
ger (they have less nonsudden cardiac and noncardiac
mortality), and at 15 and 20 years, they gained more benefit
JACC Vol. 62, No. 25, 2013 Mounsey and Schwartz
December 24, 2013:2414–5 Low Rates of High-Voltage Device Implants
2415in life span than high-risk patients from device implantation.
These findings have a direct impact on clinical practice. It is
easy for us as clinicians to evaluate our New York Heart
Association functional class III and IV patients and feel
a need to do everything we can to prolong their lives as fast
as possible. We may not see the same urgency in treating our
patients who are better compensated, especially with device
therapy. However, the authors have demonstrated that over
time, these patients actually receive more benefit from CRT.
This concept of durability of benefit is not unique to
CRT, and we believe it is evident in the non-CRT ICD
trials as well. In MADIT II, the benefit of ICD therapy was
not seen until 18 months (8). The 8-year follow-up data
showed that the absolute risk reduction was 13% and that
the NNT was 8 compared with 17 at 2 years (9). These
findings suggest that clinical benefit extends at least
throughout the life span of the device. During the trial phase
of MADIT II, two-thirds of the patients did not receive
appropriate ICD therapy. However, this relatively large
group of low-risk patients derived benefit over the longer-
term follow-up.
In a substudy of SCD-HeFT (Sudden Cardiac Death in
Heart Failure Trial), Levy et al. (10) divided the subjects
into risk quintiles. Implantation of an ICD reduced the
relative risk of sudden cardiac death by 88% in the lowest-
risk group versus a 24% reduction in the highest-risk
group. The mortality reduction was 54% in the lowest-risk
group compared with no mortality benefit in the highest-
risk group. They then looked at life span gained and found
that the lowest-risk group gained approximately 6 years but
required multiple ICDs (about 3 over their predicted life
span). This is markedly longer than the 0.2 life-year gained
for the highest-risk patients.
There is further evidence regarding the nonuniformity of
benefit of ICD therapy in the MADIT II data. Goldenberg
et al. (11) looked at their own clinical risk score to determine
who benefits the most from primary prevention ICD therapy.
They chose several clinical risk factors, including New York
Heart Association functional class >II, age >70 years, blood
urea nitrogen level >26 mg/dl, QRS duration >0.12 s, and
atrial fibrillation. They also identified a group of very-high-
risk patients with a blood urea nitrogen level >50 mg/dl
and/or serum creatinine level >2.5 mg/dl. Patients with at
least 1 risk factor had a 49% reduction in mortality, whereas
patients with no risk factors or who were deemed very high
risk had no benefit (hazard ratio: 0.96 and 1.00, respectively).
In conclusion, it seems intuitively obvious that the sickest
patients will derive the most life span benefit from prophy-
lactic high-voltage device implantation. But defibrillators,
unlike other therapies commonly used in patients with heartfailure, have a benefit that continues long after the device is
implanted. It is only by assessing this over a period of many
years and several devices that the full impact of therapy
will become apparent. The current article (9) and more
contemporary analyses of prophylactic ICD trials in different
groups of patients indicate that it is the lower-risk patients
who derive the most life span gain from these therapies. The
implication of this finding is that guideline-appropriate
patients should receive implants at an earlier stage in their
course than is currently common. The mortality benefit will
take time to become apparent, but it is real and is of impor-
tance to individual patients.
Reprint requests and correspondence: Dr. J. Paul Mounsey,
Division of Cardiology, University of North Carolina, 160 Dental
Circle, CB #7075, Chapel Hill, North Carolina 27599. E-mail:
paul_mounsey@med.unc.edu.REFERENCES
1. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of
a defibrillator in patients with myocardial infarction and reduced
ejection fraction. N Engl J Med 2002;346:877–83.
2. Camm JA, Nisam S. European utilization of the implantable defi-
brillator: has 10 years changed the ‘enigma’? Europace 2010;12:1063–9.
3. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization
therapy with or without an implantable defibrillator in advanced
chronic heart failure. N Engl J Med 2004;350:2140–50.
4. AbrahamWT, Fisher WG, Smith AL, et al. Cardiac resynchronization
in chronic heart failure. N Engl J Med 2002;346:1845–53.
5. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization
therapy for the prevention of heart-failure events. N Engl J Med 2009;
361:1329–38.
6. Linde C, Abraham WT, Gold MR, et al. Randomized trial of cardiac
resynchronization in mildly symptomatic heart failure patients and in
asymptomatic patients with left ventricular dysfunction and previous
heart failure symptoms. J Am Coll Cardiol 2008;52:1834–43.
7. Finegold JA, Raphael C, Levy WC, Winnett Z, Francis DP. Quan-
tification of survival gain from cardiac resynchronization therapy:
nonlinear growth with time, and greater gain in low-risk patients, make
raw trial data an underestimate of real-world behavior. J Am Coll
Cardiol 2013;62:2406–13.
8. Wilbur DJ, Zareba W, Hall WJ, et al. Time dependence of mortality
risk and defibrillator benefit after myocardial infarction. Circulation
2004;109:1082–4.
9. Goldenberg I, Gillespie J, Moss AJ, et al. Long-term benefit of primary
prevention with an implantable cardioverter-defibrillator. Circulation
2010;122:1265–71.
10. Levy WC, Lee KL, Hellkamp AS, Poole JE, et al. Maximizing survival
benefit with primary prevention implantable cardioverter-defibrillator
therapy in a heart failure population. Circulation 2009;120:835–42.
11. Goldenberg I, Vyas AK, Hall WJ, et al., for the MADIT-II Investi-
gators. Risk stratification for primary implantation of a cardioverter-
defibrillator in patients with ischemic left ventricular dysfunction.
J Am Coll Cardiol 2008;51:288–96.Key Words: cardiac resynchronization therapy - follow-up studies -
survival.


Why Are Clinically Indicated, But Lower-Risk, Patients Less Likely to Receive Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Therapy?*

http://citeseerx.ist.psu.edu/viewdoc/download;jsessionid=5E91CE24D1CA64D593B0FACCF8508DC3?doi=10.1.1.1039.3906&rep=rep1&type=pdf

Why Are Clinically Indicated, But Lower-Risk, Patients Less Likely to Receive Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Therapy?*

Abstract

Similar works

Full text

Available Versions

CiteSeerX