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 pound 5074 and that of a CRT-D system pound 17,266. The discounted lifetime costs of OPT, CRT-P and CRT-D were estimated as pound 9375, pound 20,804 and pound 32,689, 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 pound 15,645 per QALY. The other analysis was based on the results of the COMPANION trial and estimated an ICER of pound 2818 per QALY gained by CRT-P vs OPT and a cost per QALY gained of pound 22,384 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 pound 11,630 per person, giving an estimated ICER of pound 16,735 per QALY gained for a mixed age cohort (range pound 14,630-20,333). CRT-D vs CRT-P conferred an additional 0.29 QALYs for an additional pound 11,689 per person, giving an ICER of pound 40,160 per QALY for a mixed age cohort (range pound 26,645-59,391). 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 pound 30,000 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 pound 30,000 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 pound 40,000 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 pound 30,000 per QALY; CRT-P is cost-effective at a WTP threshold of pound 20,000 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 pound 40,160/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.
