Author + information
- aElectrophysiology Section, Division of Cardiovascular Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah
- bDivision of Cardiology, Duke University Medical Center, Durham, North Carolina
- cDuke Clinical Research Institute, Durham, North Carolina
- ↵∗Address for correspondence:
Dr. Benjamin A. Steinberg, Electrophysiology Section, Division of Cardiovascular Medicine, University of Utah Health Sciences Center, 30 North 1900 East, Room 4A100, Salt Lake City, Utah 84132.
The development of implantable cardiac devices for patients with heart failure has significantly improved clinical outcomes. Clinical trials of implantable cardioverter-defibrillators (ICDs) have demonstrated significant reductions in all-cause mortality compared with optimal medical therapy across a variety of cohorts (1). Subsequent cost-effectiveness analyses have demonstrated favorable results for ICD implantation, despite the high initial cost of the devices and procedures (2). Importantly, these data are primarily based on improvements in survival; ICDs have little effect on symptomatic heart failure outcomes.
The development of cardiac resynchronization therapy (CRT) provided a device-based approach to improved heart failure outcomes, beyond treatment of life-threatening arrhythmia. Multiple large randomized clinical trials demonstrated superior outcomes in patients assigned to CRT, with or without defibrillation capability (3). These trials have included improvements in functional status (New York Heart Association [NYHA] functional class), quality of life, and structural remodeling, as well as benefits in survival beyond that of an ICD (4).
However, as such devices have become more complex and sophisticated, costs have increased accordingly. Prior analyses have estimated the payer cost of a single-chamber ICD implant of $15,000 to $25,000 (2); the cost of a CRT defibrillator (CRT-D) implant may be upward of $35,000 or more (5). Furthermore, there remains significant heterogeneity of treatment effect for CRT; up to one-third of patients may be “nonresponders” and derive no measurable, clinical benefit, whereas others may demonstrate dramatic symptomatic and structural improvement (e.g., “super-responders”) (6). Therefore, the cost effectiveness of such an intervention is an area of great interest.
In this issue of JACC: Heart Failure, Gold et al. (7) present the results of a cost-effectiveness simulation analysis based on data from the REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) trial. The primary results of the REVERSE trial demonstrated superiority of CRT (with or without a defibrillator) over optimal medical therapy in patients with mildly symptomatic heart failure (NYHA functional classes I to II), wide QRS interval (≥120 ms), and moderate left ventricular dysfunction (ejection fraction ≤40%) (6). In the present analysis, the authors use the results of long-term extrapolation of clinical outcomes to simulate cost effectiveness of CRT in this population. They conclude that CRT in this population is cost effective based on historic U.S. benchmarks for cost (typically $50,000 per quality-adjusted life year [QALY] gained). They estimate $8,840 per QALY gained for patients receiving CRT versus no CRT overall and an additional $43,678/QALY for the use of CRT-D versus CRT-P (a non-randomized assignment).
The authors present several additional analyses, including a comparison of “early” CRT implementation (at the time of NYHA functional class II status) versus “late” (wherein the NYHA functional class II patient receives an ICD and an upgrade to CRT when they reach NYHA functional class III status). This represents an important comparison, as the earliest trials of CRT identified benefit in these sicker patients, and there has been concern about the utility and cost effectiveness of CRT in less symptomatic patients (7). The authors found that early CRT implantation did not dramatically increase costs and was associated with improved survival at an incremental cost-effectiveness ratio of $3,785 per life year gained.
Although prior analyses of ICD cost effectiveness have suggested cost effectiveness at 8 years of follow-up and beyond, the combined data for CRT cost effectiveness suggest perhaps an earlier inflection point likely due to reductions in heart failure events (e.g., hospitalizations) (5). A similar analysis from the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial—Cardiac Resynchronization Therapy) demonstrated cost-effectiveness of CRT-D compared with ICD at 4 years but limited to patients with pre-existing left bundle branch block (5). The present analysis is consistent with these findings, although the subgroup analyses are likely limited by modest power.
Overall, these data represent important contributions that inform the implementation of CRT in a fiscally responsible yet clinically effective manner. However, there are several additional important considerations. Specifically, the results of any cost-effectiveness analysis can be highly dependent on underlying assumptions of the model. In this case, the authors assumed primarily NYHA functional class II patients, averaging 63 years of age, with 2 yearly device follow-up visits, a battery longevity of 7 to 10 years, a device-related adverse event rate of 10%, and cost and other assumptions based on Medicare data. Furthermore, they relied on extrapolation of clinical outcomes of CRT beyond the primary 1-year results of the REVERSE trial. Analyses such as this are sensitive to the underlying assumptions and applicability across different healthcare systems, or payer schema is uncertain.
Another important caveat involves interpreting these cost-effectiveness data in the setting of contemporary optimal medical therapy. The REVERSE trial population had high background use of angiotensin-converting enzyme-inhibitor/angiotensin receptor blocker and beta-blockers (>95%). However, the percentage of patients receiving target doses of these medications has not been reported nor has the overall use of mineralocorticoid receptor antagonists. Moreover, these patients were not treated with other pharmacologic therapies for heart failure with reduced EF that have become available in recent years and are now recommended by current heart failure guidelines (e.g., ivabradine and combination sacubitril-valsartan). Thus, there is some degree of uncertainty with respect to the generalizability of the presently reported data to an evolving patient population.
Additionally, there is strong evidence that coronary sinus (CS) lead implant location can dramatically influence clinical response rates; this may, in turn, heavily influence the cost effectiveness of CRT. The current model was based on the clinical response rate to CRT in REVERSE, where 54% of patients receiving CRT were clinically improved (30% were unchanged) (6). They also report that 66% of CS leads were implanted laterally (ideal) and 71% in a nonapical location (optimal). However, rates of optimal CS lead implantation in real-world practice have not been well described, but they are likely to be lower than in rigorously conducted clinical trials with experienced operators. Although the present REVERSE analysis may represent an overestimate of response rate due to relatively high rates of nonapical lead positioning, it still affords room for improvement. Cardiac resynchronization therapy cost effectiveness may be even better as optimal lead deployment improves over time and with advances in technology.
Developments in CRT technology and implementation may significantly impact its cost effectiveness by both reducing costs and improving effectiveness. These developments may include improving battery technology to extend longevity and reduce generator changes; dynamic pacing approaches and hardware (e.g., quadripolar leads, multisite pacing) that improve response and also extend battery longevity; novel implantation techniques (e.g., leadless devices) that improve outcomes and reduce lead-related complications; improved implantation techniques for optimal lead deployment; and a better understanding of identifying responders, to direct therapy to those who will derive the most benefit.
In summary, in an increasingly cost-conscious environment, Gold et al. (7) provide incremental support for the cost-effective implementation of CRT in patients with mild to moderately symptomatic heart failure. These observations provide an important snapshot of the cost effectiveness of CRT in the context of a disease state that is experiencing important advances in pharmacologic therapy in concert with remarkable progress in device technology. Innovation and early adoption of invasive implantable devices should be balanced by implementation of optimal background pharmacologic therapies to most effectively optimize patient outcomes and improve the efficiency of healthcare delivery.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Dr. Steinberg has received research support from Boston Scientific; and educational support from Boston Scientific, Medtronic, St. Jude, and Biotronik. Dr. Mentz has received research support from Medtronic, Novartis, and Amgen; and honoraria from St Jude/Thoratec, and Novartis.
- 2017 American College of Cardiology Foundation
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