Cost-Effectiveness of Cardiac Resynchronization Therapy in Patients with Symptomatic Heart Failure

Context Using biventricular pacemakers to resynchronize ventricular contraction improves outcomes of heart failure in some patients. The cost-effectiveness of cardiac resynchronization is unknown. Contribution This Markov model estimates that, compared with medical therapy, cardiac resynchronization cost about $107800 per quality-adjusted life-year saved. Cautions While the cost-effectiveness of cardiac resynchronization is in the general range of other commonly used interventions, the estimates depended strongly on the authors' assumptions about mortality and hospitalization rates after cardiac resynchronization. The Editors Congestive heart failure is a common, costly, and debilitating illness. It affects an estimated 4.8 million patients in the United States, and 400000 new cases are identified every year (1). Approximately 30% to 50% of patients with heart failure have major intraventricular conduction delay, which is associated with higher risk for adverse events (2, 3). Biventricular pacemakers resynchronize the ventricular contraction to improve ejection fraction and relaxation of the left ventricle (4). However, not all therapies that improve functional outcomes in patients with heart failure reduce mortality (5). The long-term mortality, morbidity, and costs associated with cardiac resynchronization therapy remain unclear. Economic evaluation of an intervention assesses its effectiveness and costs so that decision makers can decide whether it is good value for the money. If cardiac resynchronization is effective and inexpensive, then the lives of thousands will be improved annually. If not, then limited health care resources can be invested in other interventions that are better value for the money. We used decision analysis to estimate the incremental cost-effectiveness of cardiac resynchronization therapy versus medical therapy. Methods Our target population was patients with reduced ventricular function and prolonged QRS. The decision model compared the lifetime effects and costs of cardiac resynchronization therapy and medical therapy in patients with congestive heart failure. We made the following assumptions about the costs and effects of cardiac resynchronization. Unit costs of complications related to cardiac resynchronization were identical to those for implantable cardioverter defibrillators, since the costs of insertion of either device were similar (Table 1) (10). Unit costs of heart failure therapy (that is, costs of outpatient or inpatient care) were otherwise identical for medical therapy and cardiac resynchronization. The incidence of complications associated with cardiac resynchronization was constant over time from implantation. Any mechanical malfunction of the device required battery replacement, with consequent costs and consequences. Uncomplicated cardiac resynchronization and medical therapy yielded identical health-related quality of life. The utility for hospitalization was identical for both therapies regardless of the reason for hospitalization. We incorporated the morbidity of hospitalization into the model by assigning the utility for hospitalization to its duration and assigning the utility for the health state before hospitalization to the remainder of the cycle. Finally, age-specific mortality due to unrelated causes was based on life tables (11). Structure of the Decision Model The base-case analysis considered patients with New York Heart Association (NYHA) class III heart failure. The analysis considered the lifetime horizon, as recommended elsewhere (12). A state-transition Markov model compared costs and outcomes of congestive heart failure treated with cardiac resynchronization therapy versus medical therapy. A cycle length of 1 month was used. During each cycle, patients who received medical therapy could die, be hospitalized for heart failure, or remain stable (Figure 1). Patients who underwent insertion of a device capable of cardiac resynchronization could die during the initial implantation; experience lead infection, lead failure, and battery failure; or experience any of the health states associated with medical therapy for heart failure (Figure 2). Figure 1. Markov model of medical therapy for heart failure. Figure 2. Markov model of cardiac resynchronization therapy ( CRT ) for heart failure. The reference-case analysis considered only the effect of resynchronization on all-cause mortality, since it is difficult to subclassify causes of death in patients with cardiovascular disease (13). The concurrent systematic review (14) considered death due to any cause, cardiac death, and sudden cardiac death separately. However, the pooled relative risk for cardiac death and sudden cardiac death was based on retrospective subgroup analyses of data observed in the randomized trials of cardiac resynchronization therapy. Such post hoc determinations may be susceptible to bias. Therefore, cardiac and noncardiac death were considered only in secondary economic analyses that accounted for patient age at implantation (that is, differences in mortality due to unrelated causes). Decision analyses were performed by using DATA Pro (TreeAge Software, Inc., Williamstown, Massachusetts) and Excel 2000 (Microsoft Corp., Redmond, Washington). Statistical analyses were performed with S-PLUS (Insightful Corp., Seattle, Washington). Input Data Survival and Hospitalization We obtained the probabilities of cardiovascular death, arrhythmic death, death from heart failure, hospitalization for heart failure, and adverse effects associated with either therapy from a concurrent systematic review (14). Nine trials were included in the efficacy analysis: a study from the Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators examining sinus rhythm (4); a study from the MUSTIC Study Investigators examining atrial fibrillation (15); a trial by Garrigue and colleagues (16); the Pacing Therapies for Congestive Heart Failure (PATH-CHF) trial (17); a trial examining the safety and effectiveness of the Guidant Cardiac Resynchronization Therapy Defibrillator System (CONTAK-CD) (18); the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) (19, 20); the Multicenter InSync Randomized Clinical Evaluation Implantable Cardioverter Defibrillator (MIRACLE-ICD) (21); the Comparison of Medical Therapy, Pacing and Defibrillation in Chronic Heart Failure (COMPANION) (22); and 1 trial that remains unpublished (Leclercq C, Alonso F, d'Allones FR, et al. Effets moyen terme de la stimulation multisite biventriculaire dans l'insuffisance cardiaque svre. Personal communication. May 2003). We annualized the rate of events observed among patients randomly assigned to medical therapy by using an exponential approximation (23, 24). Transition probabilities incorporated into the Markov model were adjusted for the cycle length. Pooled relative risks were calculated by using fixed-effects methods (25). Quality of Life We estimated the health-related quality of life of patients with heart failure by eliciting utilities (Appendix), since current standards suggest that use of such outcome measures (7) and the relative cost-effectiveness of some cardiac therapies are sensitive to the difference between the utilities associated with either treatment (8). The general public was surveyed because the analysis considered resource allocation among different types of interventions (that is, medical therapy vs. resynchronization) rather than allocation for a single intervention (7). Costs The economic analysis was conducted from a health care perspective, including costs of hospitalization, procedures, and laboratory tests. Costs were expressed in 2003 U.S. dollars (Table 1). The costs of insertion of a resynchronization-capable device were based on a survey of manufacturers' list prices. Physician costs related to cardiac resynchronization were based on Current Procedural Terminology codes (26). The costs of hospitalizations associated with congestive heart failure were based on estimates derived from a cohort study of health resource use by patients participating in a previous randomized trial of medical therapy for heart failure (9). All costs were adjusted for inflation by using the U.S. Consumer Price Indexes (27). Table 1. Input Data Uncertainty and Variability Analyses The analysis distinguished between parameter uncertainty (that is, variation in costs and effects due to sampling and measurement error) and variability (that is, heterogeneity in costs and effects between groups of patients with systematic differences in cost or effects). Uncertainty was assessed by using 10000 probabilistic Monte Carlo simulations (28, 29). Empirical cost variables were assigned log-normal distributions, and empirical probability variables were assigned distributions (28). Variables without a known distributional form (that is, those with assumed values or those with values based on a range of published reports) were assigned triangular distributions (30). Since there is no absolute cost-effectiveness criterion (31), the results of the Monte Carlo simulation were illustrated as a scatter plot of incremental effects in quality-adjusted life-years (QALYs) versus incremental costs. In such a plot, the incremental cost-effectiveness ratio is represented by the slope of incremental costs to incremental effects. The uncertainty in costs and effects was also illustrated as a cost-effectiveness acceptability curve (32-34). An acceptability curve is a conditional probability plot showing the proportion of the observed incremental cost-effectiveness density that lies below a threshold ratio (), which represents the monetary value of a QALY. The plot is conditional on , and therefore the decision maker can interpret the data relative to the threshold willingness to pay for the incremental health outcome. Variability was assessed by using sensitivity analyses. We replaced the value of each variable in the decision model with its uppe