Title: REVascularisation of Ischaemic VEntricular Dysfunction (REVIVED): a randomised comparison of percutaneous coronary intervention (with optimal medical therapy) vs. optimal medical therapy alone for heart failure secondary to coronary disease
Funder: Department of Health and Social Care

Abstract: DESIGN: prospective, randomised, controlled, multi-centre trial HEALTH TECHNOLOGY BEING ASSESSED: It is unclear whether any form of revascularisation is beneficial in heart failure due to coronary artery disease (CAD). Coronary artery bypass graft surgery (CABG) has been beneficial in previous registries but the increased mortality associated with surgery may offset the benefits. Percutaneous Coronary Intervention (PCI) is a lower risk procedure and is the most widely employed treatment for CAD, with 80,000 procedures carried out annually in the UK, at a ratio of 3.25 to 1 in relation to CABG. The two main indications for PCI at present are acute myocardial infarction (or acute coronary syndrome) and stable exertional angina. Treatment of severe left ventricular impairment (in the absence of limiting angina) is not an established indication for PCI and is the subject of the proposed study. TARGET POPULATION: Patients with poor LV function (EF=30%) significant CAD (Jeopardy Score =6) AND viable myocardium (=30% of dysfunctional segments) will be eligible and those with significant angina (=CCS class 3) or a recent myocardial infarction (< 6 weeks) will be excluded. SETTING: 25-30 tertiary care cardiac units in the UK MEASUREMENT OF OUTCOMES/COSTS:The primary outcome measure is the composite of all-cause death and hospitalisation due to heart failure. Major Secondary outcome measures include Quality of Life scores (EQ5D, KCCQ), NHYA functional class and LV function at 6 months and 1 year. Other outcome measures include the need for further revascularisation, cardiovascular death or acute MI and NHS resource use. An analysis of cost effectiveness will be carried out based on the evidence collected within REVIVED-BCIS2 and existing data. SAMPLE SIZE: The predicted occurrence of death or hospitalisation for heart failure at two years is 36% in the OMT group. The primary endpoint in REVIVED-BCIS2 will be measured over the entire trial duration (i.e. up to 66 months for some patients) with a minimum follow-up duration of two years, thus increasing the number of events. A trial of 700 (350 in each group) would have over 85% power to detect a hazard ratio of 0.7 (a 30% relative reduction in the hazard) at 5% significance allowing for up to 5% losses by the end of follow-up and increasing recruitment over time. For illustrative purposes this represents a reduction to 27% of patients with an event in the PCI group at two years. These calculations are based on patient accrual for 42 months and minimum follow-up of 24 months (range 24-66 months). The above predicted event rates are conservative in relation to the existing literature, and take into account the possibility of patients randomised to OMT subsequently undergoing PCI (see below). If a higher event rate is found in the OMT group or patient recruitment rates exceed expectation early in the trial (thus providing a longer duration of follow-up in a larger proportion of patients), the study would have greater power to detect a hazard ratio of 0.7, or alternatively, provide over 85% power to detect smaller differences in treatment effect. Although a smaller treatment effect may be clinically significant, this would have a major impact on sample size, which in turn may affect the feasibility of completing the trial within the proposed timescale and resources. The hazard ratio of 0.7 used in the power calculation is pragmatic, while being clinically meaningful and is in line with the magnitude of benefit observed across other treatment modalities in this population. The study is expected to have very good power to detect differences in Quality of Life (one of the major secondary outcomes). PROJECT TIMETABLE: Start date – 1st June 2013. Recruitment period – 42 months (1st September 2013 to 1st March 2017). Minimum follow-up - 2 years (range 24-66 months) Recruitment rate – Approximately 8 patients per centre per year across 25-30 centres. Estimated date of first presentation of results - Q4 2019

Lay abstract: Heart failure causes debilitating symptoms and accounts for more than 1 in 20 deaths in the UK. The cost to the NHS was £625 million per year a few years ago and is expected to increases several-fold in the next two decades. Narrowing of the heart arteries is the cause in most instances and several previous studies have indicated that the quality of life and longevity of those suffering from heart failure can be improved by treating these narrowings by angioplasty or surgical procedures. However, owing to paucity of robust data from carefully designed studies, there is no expert consensus on how such patients should be managed and few are offered this treatment option at present. The proposed study will use scientifically validated methods to carry out the largest study to date in this group of patients, across several cardiac centres in the UK. It will assess whether angioplasty to heart arteries can improve survival and reduce major symptoms in patients with heart failure compared to a tablet-based strategy alone. The results of this study have the potential to rationalise and improve the care of patients with heart failure and by improving outcomes, translate to more efficient utilisation of NHS resources. The current team is well placed to carry out this study as it is comprised of individuals who specialise in treating heart failure and narrowed heart arteries. Individually and collectively, they have an established track record of research in cardiology and recently concluded a multicentre trial of angioplasty in heart failure patients, the largest of its kind to date, albeit addressing a distinct research question to the current study. The research network they have established in the UK during the course of their previous research will allow this important project to be performed in a timely manner at the lowest possible cost.

Research activity codes: 6.4 SURGERY;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CARDIOVASCULAR