REvascularisation for heart failure with PReserved ejection fraction and Ischaemia: EValuation of Efficacy and mechanistic Description (REPRIEVED)

Research question

Does percutaneous coronary intervention (PCI) improve quality of life by relieving ischaemia in patients with heart failure with a preserved ejection fraction (HFpEF) and coronary artery disease? Background

HFpEF is a debilitating condition which causes breathlessness, fatigue and frequent hospitalisations. Coronary artery disease causes ischaemia and contributes to the development of HFpEF in 50% of patients. There is currently no disease specific therapy for patients with HFpEF and coronary artery disease.

Coronary artery revascularisation with PCI is widely used to treat angina and myocardial infarction where it is effective in relieving ischaemia and improving symptoms; whether the same is true for HFpEF has not been investigated. Aims

To determine whether, in representative patients and ideal circumstances, PCI improves quality of life (efficacy outcome) and reduces ischaemia (mechanistic outcome) in individuals with HFpEF and coronary artery disease, compared to a placebo procedure. Methods Design: Phase-II, prospective, multi-centre, randomised, double-blind, placebo procedure-controlled trial.

Target Population: Individuals with a diagnosis of HFpEF (per European Society of Cardiology Diagnostic Criteria) and significant coronary artery disease (fractional flow reserve = 0.80 in at least one major epicardial coronary artery) will be enrolled.

Screening: Individuals with HFpEF who have not undergone a recent clinical assessment for coronary artery disease will be screened with CT coronary angiographic fractional flow reserve (CT-FFR). Sample size: 350 participants. Intervention: PCI to all significantly diseased coronary arteries. Comparator: Placebo PCI procedure.

Randomisation: 1:1 using online randomisation system, stratified by trial centre.

Assessment and follow-up: All participants will complete baseline assessments of quality of life, medical history, ECG, blood tests and a transthoracic echocardiogram. Quality of life and SAEs will be recorded at 3 months, and all study assessments repeated at final follow-up at 6 months.

Mechanistic sub-study: Coronary flow reserve (CFR), fractional flow reserve (FFR), and microvascular resistance reserve (MRR) measured during cardiac catheterisation.

Outcomes: The primary efficacy outcome is the difference in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) between groups at 6-month follow up. The primary mechanistic outcome is the difference in CFR from pre- to post-PCI. Equality, diversity and inclusion (EDI)

A dedicated EDI work package to ensure representative recruitment and study investigating diversity in heart failure trials. Timelines for delivery

The project duration is five years. After nine months of set-up, participants will be recruited over 3-years. Follow up will continue for six months. The final nine months will be dedicated to data entry, database lock, site close out, dissemination, completion of the NIHR final report and determining the feasibility, design and funding of a subsequent phase 3 trial.

Anticipated impact and dissemination

If effective this would be the first disease-specific treatment for HFpEF and coronary artery disease. Dissemination will be via scientific publication, presentation and public dissemination via newspapers, internet articles and podcasts. Participants will be invited to a results webinar or receive results from their local research team.