The clinical effectiveness and cost-effectiveness of cardiac resynchronisation (biventricular pacing) for heart failure: systematic review and economic model.

OBJECTIVES To assess the clinical effectiveness and cost-effectiveness of cardiac resynchronisation therapy (CRT) for people with heart failure and evidence of dyssynchrony by comparing cardiac resynchronisation therapy devices, CRT-P and CRT with defibrillation (CRT-D), each with optimal pharmaceutical therapy (OPT), and with each other. DATA SOURCES Electronic databases were searched up to June 2006. Manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE) were also searched for additional evidence. REVIEW METHODS Relevant data from selected studies were extracted, narrative reviews were undertaken and meta-analyses of the clinical trial data were conducted. A Markov model was developed. Incremental costs and quality-adjusted life-years (QALYs) were calculated. Extensive one-way sensitivity analyses, threshold analyses, probabilistic sensitivity analyses and value of information analyses were carried out. RESULTS Five randomised controlled trials met the inclusion criteria, recruiting 3434 participants. Quality was good to moderate. Meta-analyses showed that both CRT-P and CRT-D devices significantly reduced the mortality and level of heart failure hospitalisations and they improved health-related quality of life in people with New York Heart Association (NYHA) class III and IV heart failure and evidence of dyssynchrony (QRS interval >120 ms) who were also receiving OPT. A single direct comparison indicated that the effects of CRT-P and CRT-D were similar, with the exception of an additional reduction in sudden cardiac death (SCD) associated with CRT-D. On average, implanting a CRT device in 13 people would result in the saving of one additional life over a 3-year period compared with OPT. The NHS device and procedure cost of implanting a new CRT-P system (pulse generator unit and required leads) was estimated to be 5074 British pounds and that of a CRT-D system 17,266 British pounds. The discounted lifetime costs of OPT, CRT-P and CRT-D were estimated as 9375 British pounds, 20,804 British pounds and 32,689 British pounds, respectively. The industry submissions to NICE contained four cost-effectiveness analyses, of which two were more appropriate as reference cases. One used a discrete event simulation model that gave estimated incremental cost-effectiveness ratios (ICERs) of CRT-P vs OPT of 15,645 British pounds per QALY. The other analysis was based on the results of the COMPANION trial and estimated an ICER of 2818 British pounds per QALY gained by CRT-P vs OPT and a cost per QALY gained of 22,384 British pounds for CRT-D vs OPT. Compared with OPT, the Markov model base case analysis estimated that CRT-P conferred an additional 0.70 QALYs for an additional 11,630 British pounds per person, giving an estimated ICER of 16,735 British pounds per QALY gained for a mixed age cohort (range 14,630-20,333 British pounds). CRT-D vs CRT-P conferred an additional 0.29 QALYs for an additional 11,689 British pounds per person, giving an ICER of 40,160 British pounds per QALY for a mixed age cohort (range 26,645-59,391 British pounds). The authors' ICERs are higher than those from the industry-submitted analysis. Probabilistic sensitivity analysis based on 1000 simulated trials showed that, at a willingness-to-pay (WTP) threshold of 30,000 British pounds per QALY, in CRT-P versus OPT, CRT-P was likely to be cost-effective in 91.3% of simulations and that CRT-P was negatively dominated in 0.4% of simulations. It also showed that in CRT-P versus CRT-D, CRT-D was likely to be cost-effective in 26.3% of simulations and that CRT-P dominated CRT-D in 7.8% of simulations. The relative risk for SCD when CRT-D is compared with OPT is 0.44 in the base case. This treatment becomes cost-ineffective at a WTP threshold of 30,000 British pounds when this value is greater than 0.65. When both CRT-P and CRT-D were considered as competing technologies with each other and OPT (three-way probabilistic analysis), and at the same WTP, there was a 68% probability that CRT-P provided the highest expected net benefit. The WTP threshold would need to be above 40,000 British pounds before CRT-D provided the highest expected net benefit. CONCLUSIONS The study found that CRT-P and CRT-D devices reduce mortality and hospitalisations due to heart failure, improve quality of life and reduce SCD in people with heart failure NYHA classes III and IV, and evidence of dyssynchrony. When measured using a lifetime time horizon and compared with optimal medical therapy, the devices are estimated to be cost-effective at a WTP threshold of 30,000 British pounds per QALY; CRT-P is cost-effective at a WTP threshold of 20,000 British pounds per QALY. When the cost and effectiveness of all three treatment strategies are compared, the estimated net benefit from CRT-D is less than with the other two strategies, until the WTP threshold exceeds 40,160 British pounds/QALY. Further research is needed into the identification of those patients unlikely to benefit from this therapy, the appropriate use of CRT-D devices, the differences in mortality and heart failure hospitalisation for NYHA classes I and II, as well as the long-term implications of using this therapy.