DISCUSSION
left ventricle systolic dysfunction, Angioplasty, coronary artery disease
REGRESSION, DISEASE, CORONARY ARTERY DISEASE, STABLE ANGINA
In this prospective within-trial cost-effectiveness analysis of the REVIVED trial, no appreciable difference in total QALYs was identified between arms, but the PCI+OMT strategy was substantially more expensive than OMT alone, largely due to the upfront cost of PCI. Consequently, PCI+OMT was economically dominated and not cost-effective compared with OMT. When parameter uncertainty is allowed, there was no probability of PCI+OMT being cost-effective at a threshold of ≥£20 000 per QALY. The clinical results of REVIVED were neutral for the comparison of strategies, with no safety concerns raised with PCI, in contrast to the STICH trial where CABG was associated with a 3-fold to 4-fold excess in mortality within the first 2 years following randomization.No prior study has reported on the incremental costs of the PCI against relevant comparators for patients with ILVD. Our findings are in contrast to the economic analysis performed on the STICH trial data.Economic analyses of revascularization by PCI have also been performed for the COURAGE (Clinical Outcomes Utiliz- ing Revascularization and Aggressive Drug Evalu- ation) and ORBITA (Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina) trials in patients with stable coronary artery disease although these studies specifically excluded patients with severe left ventricle systolic dysfunction and multivessel disease. Notwithstanding the important differences in target populations, different settings (United States and United Kingdom), modeling assumptions (within trial and model based), and comparators (best MT and placebo), the results of the aforementioned analyses support the view of some disparity in the economic value of PCI.The clinical results of REVIVED were neutral for the comparison of strategies, with no safety concerns raised with PCI, in contrast to the STICH trial where CABG was associated with a 3-fold to 4-fold excess in mortality within the first 2 years following randomization.A strength of this economic analysis was the relatively long study follow-up period (up to 8 years; median, 3.4 years). This offers a good understanding of the medium- to long-term costs and benefits of the strategies being evaluated. While a lifetime analysis could have been conducted, the results of this 8-year analysis indicated that this was unnecessary. Given the clinical, cost-related, and health-related quality-of-life results that we have reported, there seems to be unlikely a scenario in which long-term costs and outcomes would make PCI a cost-effective treatment, and we think that it is reasonable to conclude that estimated cost-effectiveness over an 8-year time horizon is generalizable to the patient’s lifetime. For this reason, no modeling to extrapolate evidence from the trial to the long term was considered necessary.By using regression analyses in our study, we aimed to provide an unbiased estimate of the expected costs and health outcomes associated with each treatment, as should be the objectives of any cost-effectiveness analysis. By describing the relationship between the outcome of interest and treatment assignment, it helped us identify the expected costs and outcomes associated with the comparator treatment. The regression framework also enabled a characterization of the decision uncertainty from which an assessment of the need for any additional research could be made. A note that the uncertainty expressed in the cost-effectiveness estimates presented relate to second-order uncertainty (uncertainty around the mean for the average patient with severe ILVD) and is subject to structural uncertainty (uncertainty relating to the form of regression model implemented). On the latter, model specification may hinder an appropriate reflection of parameter uncertainty, which may be reflected in the relatively narrow CIs of the predicted total costs. With its advantages and disadvantages, alternative modeling has been implemented through a seemingly unrelated regression model.The study has some limitations. The resource uses collected within the REVIVED trial are believed to be comprehensive though the aim of our study was not to estimate the total cost burden of ILVD but to capture cost and QALY differences between therapies here under scrutiny. Nevertheless, and as with many trial analyses, there are practical limits to what has been collected. For example, the total number of clinical tests performed on trial patients is likely to exceed what was captured in the case report form as only mandated tests to inform the specified clinical outcomes were captured. The total cost of managing these patients is likely to be appreciably higher than we have estimated; however, these uncaptured costs are likely to be distributed evenly between groups. Another potential limitation of our work is that medication data were collected only for the initial 2 years of follow-up. These limitations apply to both study arms and are unlikely to impact the overall conclusions of the analysis. A sensitivity analysis using alternative unit costs from NHS Reference Costs 2020/2021Health-related quality of life collected via the EQ-5D-5L questionnaire contained a proportion of missing data. This was due to a small proportion of patients being lost to follow-up, being too unwell to complete the questionnaires, and limitations in face-to-face visits due to the COVID-19 pandemic. It was assumed that systematic differences between the missing and observed EQ-5D index scores existed, but these could be entirely explained by other observed variables. Thus, multiple imputation was used to address missingness, generate multiple imputed data sets, and achieve a similar time frame of analysis, providing a fuller understanding of the health-related quality-of-life data. This approach allowed us to account for any gaps or missing values in the per-patient QALY calculations and ensure a comprehensive evaluation of the health outcomes for both the OMT and PCI+OMT arms.Finally, our analysis is based specifically on costs relating to the UK NHS and cannot, therefore, be directly transferable to other health systems. The costs of PCI are relatively low in the publicly funded NHS by comparison with privately funded health care systems, such as the United States. If similar health resource consumption and health-related quality of life are assumed, a higher cost for PCI would augment overall costs further and further increase its negative economic impact.In summary, our results have identified that, for patients with severe ILVD in the United Kingdom, revascularization using PCI in addition to OMT is not considered to be cost-effective when compared with OMT alone, given its additional cost. These conclusions were robust to different modeling assumptions and unit costs. Routine use of PCI for the treatment of severe ILVD does not seem to be a justifiable use of the UK NHS resources.