BACKGROUND/RATIONALE:
Until recently, implantable cardioverter-defibrillators (ICDs) have primarily been implanted in patients who have survived episodes of sudden cardiac death or other life-threatening arrhythmias (secondary prevention). However, recent trials have demonstrated statistically significant, but relatively modest, improvements in survival in both myocardial infarction survivors and patients with heart failure who have reduced ejection fractions (primary prevention). Approximately 1.5 million patients presently meet these criteria, as will an estimated 500,000 additional patients each year. As a result, ICD implantation rates have increased by 40-50% annual for the past 2 years and this is expected continue or accelerate, and ICD implantation costs are expected to grow from $1.5 billion to $10-20 billion over 10 years.
As noted, although clearly evident, the survival benefit in the primary prevention trials has been modest, ranging from 7-10 lives saved over 3-5 years per 100 patients implanted, with some important subgroups showing no benefit. Furthermore, patients enrolled in these clinical trials enrolled populations that differed substantially from the general population who would meet the eligibility criteria, in that they were younger, contained fewer women, and suffered from fewer serious comorbid conditions.
For these reasons, it is critical that further studies delineate the characteristics differentiate patients who receive ICDs who demonstrate the most benefit (e.g, receive ICD "shocks" or antitachycardia pacing) and have meaningful subsequent survival, and those who show limited benefit (no ICD therapy delivered or only brief survival subsequent to therapy.
This proposal will utilize the unique data available from National ICD Surveillance Center (NISC), located at the San Francisco VAMC and the VA electronic medical record to identify predictors of benefit and lack of benefit in the rapidly expanding population of Veterans receiving ICDs. In addition, we will determine the cost-effectiveness of ICDs in the VA system.
OBJECTIVE(S):
We propose to utilize the unique information available through the VA National ICD Surveillance Center (VANISC) to develop methods for predicting the clinical outcomes and estimating the cost-effectiveness associated with ICD therapy in Veteran patients and subgroups among individual Veterans.
The specific aims are:
1. To determine the demographic and clinical characteristics of Veteran ICD recipients, the indications for ICD placement, and the appropriateness of ICD placement compared with guideline recommendations.
2. To determine patient characteristics that predict low and high risk of appropriate ICD discharges.
3. To identify baseline characteristics that stratify patients based upon their likelihood of benefit from ICD implantation, and develop a prediction model incorporating these characteristics.
4. To estimate the cost-effectiveness of ICD implantation in veterans across a broad spectrum of arrhythmia and mortality risk.
METHODS:
We will conduct a prospective cohort study utilizing data from 10,000-15,000 Veterans who will have ICDs implanted and are enrolled in the San Francisco based VA NISC by the end of 2008. This "real world" cohort is not subject to either the restrictive entry criteria or selection biases of randomized clinical trials or the reimbursement restrictions that apply to non-VA patients.
Information concerning patients' demographic and clinical characteristics; indication for ICD placement; ICD type, programming, and activity; clinical outcomes; and resource utilization will be collected from the implanting team, review of electronic medical record, periodic downloading of stored ICD data; and appropriate VA databases.
Multi-predictor regression models will be used to assess secular trends in patient characteristics and indications for ICD placement. Cox and tree-structured survival methods will be used to develop prediction rules with potential policy implications, using generalized cross-validation methods to obtain reliable estimates of the likely prediction error of the derived rules. Cost-effectiveness will be assessed in patients across a range of indications and risk predictors by projecting life expectancy and lifetime cost of care using actual survival and cost information from the period of observation.
FINDINGS/RESULTS:
In preliminary analyses, between January 1, 2003 and December 31, 2005, a total of 1157 patients met our study entry criteria; such subjects underwent implantation of a first ICD within the VA system and were enrolled in the VA National ICD Surveillance Center (VANISC) remote monitoring program within three months of implantation. This did not include veterans whose devices were implanted at non-VA hospitals or at VA hospitals who were not yet participating in VANISC. We found that the overwhelming majority (89%) of devices were implanted for primary prevention of sudden cardiac death, and the level of comorbidity was higher than that seen in randomized trials. Surprisingly, with a median follow-up of 2.5 years, we observed a rate of all-cause mortality of 7.7 per 100 person years. The 14% mortality we observed at two years compares well with the range of 2-year mortality observed in the major randomized trials of primary prevention ICD therapy, MADIT (12%), MADIT-2 (16%), and SCD-HeFT (11%), despite older subjects and greater burden of comorbidity among our cohort of veterans with ICDs.
IMPACT:
The proposed analyses, derived from a population-based cohort of unselected Veterans receiving ICDs with robust long-term clinical and device performance data, will provide unique information about who is receiving these devices, how they are being used, which patients experience ICD discharges and which do not, and what are the attendant costs and adverse effects. The proposed analytic approaches will identify predictors of patients who are very unlikely or very likely to benefit from ICD implantation, and the key determinants of cost-effectiveness. This information should be valuable in informing clinical decision-making and clinical practices, supporting guideline development, and influence policy and planning with regard to ICD utilization.
In recognition of the importance of addressing these and other questions, the Center for Medicare/Medicaid Services (CMS) has now required all patients with ICD implantations reimbursed by CMS to be enrolled in a data registry, which is being managed by the American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR) program. We have carefully coordinated the data collection process and some variable definitions of our own study to allow for symmetrical studies and collaboration between our studies. Both Drs. Heidenreich and Varosy are members of the Science and Publications committee of the ACC-NCDR ICD Registry.
PUBLICATIONS:
Journal Articles
- Massie BM, Fabi MR. Clinical trials in diastolic heart failure. Progress in Cardiovascular Diseases. 2005; 47(6): 389-95.
- Packer M, McMurray J, Massie BM, Caspi A, Charlon V, Cohen-Solal A, Kiowski W, Kostuk W, Krum H, Levine B, Rizzon P, Soler J, Swedberg K, Anderson S, Demets DL. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: results of a pilot study. Journal of Cardiac Failure. 2005; 11(1): 12-20.
