Coronary artery stents in heart failure with preserved ejection fraction

ISRCTN ISRCTN12843546
DOI https://doi.org/10.1186/ISRCTN12843546
IRAS number 330189
Secondary identifying numbers CPMS 56787, NIHR159715
Submission date
02/05/2025
Registration date
03/06/2025
Last edited
03/06/2025
Recruitment status
Not yet recruiting
Overall study status
Ongoing
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Heart failure with preserved ejection fraction (HFpEF) is a serious medical condition where the heart muscle stiffens and is unable to properly pump blood around the body. The main symptoms are difficulty breathing, tiredness and leg swelling. HFpEF can be linked to other medical conditions such as high blood pressure, diabetes, kidney failure and obesity as well as age. It is more likely to affect women and people of non-White ethnicities than other types of heart failure. There are very few treatments for HFpEF.
Half of people with HFpEF have coronary artery disease, blockages in the blood vessels which supply the heart. These blockages are thought to be the cause of heart failure. Stents are small metal tubes that are used to unblock arteries in a keyhole operation so that blood can flow normally. Research shows that they are a good treatment for heart attacks and angina in patients without heart failure. They are quite safe, with a 1 in 200 risk of a major complication and 1 in 10,000 risk of dying from a planned stent procedure.
We think that stents will help people with HFpEF and coronary artery disease but need research to prove this. This study will help us to answer this question. The team running the study is an equal partnership of doctors, researchers and patients.
The REPRIEVED trial aims to find out if treating people with HFpEF and coronary artery disease with stents improves their quality of life and blood supply to their heart.

Who can participate?
Patients aged 18 years and over with a diagnosis of HFpEF and coronary artery disease

What does the study involve?
Participants are randomly allocated to one of two groups:
Intervention group: Participants will receive percutaneous coronary intervention (PCI) as per current standard of care.
Control group: Participant will undergo a placebo PCI procedure that involves placement of a thin tube to image the blood vessel but does not involve placement of an actual stent.

What are the possible benefits and risks of participating?
Possible risks:
There are some risks that it is important to be aware of if you decide to take part in this study. Some people who have not had a previous angiogram will be asked to have a CT coronary angiogram of their coronary arteries. This will allow us to see if they have coronary artery disease and if they can take part in the trial. All people taking part in the study will have a coronary angiogram and you may have a stent procedure (depending on the treatment group you are assigned to). All of these procedures can be extra to those that you would have if you did not take part in this study. These procedures use ionising radiation to form images of your body and provide treatment. Ionising radiation may cause cancer many years or decades after the exposure. In patients with your current clinical condition, the chance of this happening to you is extremely small.
A coronary angiogram can involve a special wire called a pressure wire study procedure. This procedure involves putting a thin tube (catheter) through the arm or groin to take pictures of the coronary arteries and measure how well they function. A special dye (called contrast) is injected during the procedure. The procedure is in regular use to assess patients with angina or heart attacks across the National Health Service (NHS). It is performed by specially trained heart doctors (cardiologists) called interventional cardiologist. It is done using local anaesthetic and with medication to make people sleepy.
For all people receiving treatment including those in the placebo group, the risks of an angiogram and pressure wire study include minor bleeding (1 in 50 procedures), major bleeding (1 in 500 procedures), bleeding round the heart (1 in 2000 procedures), damage to the blood vessels (1 in 1000 procedures), heart attack (1 in 1000 procedures), stroke (1 in 2000 procedures) allergic reaction to contrast dye (1 in 1000 procedures) and damage to the kidneys from injected contrast dye (1 in 2000 procedures). The risk of death from a planned test such as this is around 1 in 10,000 procedures. The overall risk of a major complication is around 1 in 400 procedures. This means that 99.75% of patients will not have a complication.
In the people who receive the stent procedure, there will be an additional step where stents are placed within the coronary arteries. Balloons are used to stretch open the narrowings, and stents (small expandable metal tubes) are used to hold them open. The risks of these procedures are the same as for the angiogram but occur slightly more often as the procedure is more complex. The specific increased risks are of heart attacks (1 in 500), stroke (1 in 1000), damage to the kidneys (1 in 500) and death (1 in 2000). The overall risk of a major complication is around 1 in 200 procedures. This means that 99.5% of people will not have a complication.
After the procedure, people will receive medication to thin their blood. Aspirin will be prescribed to all people who take part as this is needed to treat their coronary artery disease. A second medication, called clopidogrel, will be prescribed to people who take part and receive stents. This is to stop blood clots from forming inside the stents for 12 months. These medications are routinely given to people who have stents inserted for heart attacks or angina. Taking both of these medications together increases the risk of bleeding. It is common that people notice that they bruise more easily when taking clopidogrel. The risk of major bleeding from taking aspirin and clopidogrel, as opposed to aspirin alone, is 1 in 100 over 12 months. There is no increased risk of life-threatening bleeding. People who do not receive stents will not take clopidogrel (and instead they will receive a placebo tablet).

Possible benefits:
As we do not know whether the use of stents is helpful, we cannot say whether or not there will be a direct benefit to you. The information that we get when people take part may benefit people living with HFpEF and coronary artery disease in the future.
The trial will give us a better understanding of how well stent procedures work to treat people with these heart conditions. If it does work, then it could be used in the NHS in the future. If the stent procedures does not work well in this setting, then we will still have learned important information about what research needs to be done in the future to improve treatments for people living with HFpEF and coronary artery disease.

Where is the study run from?
The study is being run by the London School of Hygiene & Tropical Medicine (LSHTM) Clinical Trials Unit (CTU) (UK)

When is the study starting and how long is it expected to run for?
September 2024 to August 2029

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
REPRIEVED Clinical Trials Unit, REPRIEVED@lshtm.ac.uk

Study website

Contact information

Dr Matthew Ryan
Scientific

The Rayne Institute
4th Floor Lambeth Wing
St Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom

Phone +44 (0)2071881041
Email matthew.ryan@kcl.ac.uk
Mr Matthew Kwok
Public

London School of Hygiene and Tropical Medicine
Keppel Street
London
WC1E 7HT
United Kingdom

Email REPRIEVED@lshtm.ac.uk

Study information

Study designRandomized controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleREvascularisation for heart failure with PReserved ejection fraction and Ischaemia: EValuation of Efficacy and mechanistic Description (REPRIEVED)
Study acronymREPRIEVED
Study objectivesEfficacy:
1. In patients with heart failure with preserved ejection fraction (HFpEF) and coronary artery disease, treatment with percutaneous coronary intervention (PCI)is associated with superior quality of life, measured with the Kansas City Cardiomyopathy Questionnaire - Overall Summary Score (KCCQ-OSS), compared to a placebo procedure.

Mechanistic:
1. In patients with HFpEF and coronary artery disease, the severity of symptoms correlates with the extent of myocardial ischaemia measured by coronary flow reserve (CFR).
2. Treatment of epicardial coronary disease by PCI will improve CFR.
3. The change in quality of life following PCI correlates with the change in CFR.
Ethics approval(s)Approved 06/05/2025, London - Riverside Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, UK; +44 (0)207 104 8150, (0)207 104 8243; riverside.rec@hra.nhs.uk), ref: 25/LO/0277
Health condition(s) or problem(s) studiedHeart failure with preserved ejection fraction (HFpEF) and coronary artery disease
InterventionPatients with HFpEF and coronary artery disease will be randomised 1:1 using an online randomisation system to either PCI (intervention group) or placebo procedure (control group) using an online randomisation system in permuted blocks of varying size and stratified by recruiting site.

Intervention group: Participants will receive percutaneous coronary intervention (PCI) as per current standard of care.
Control group: Participant will undergo a placebo PCI procedure that involves placement of a thin tube to image the blood vessel but does not involve placement of an actual stent.
Intervention typeProcedure/Surgery
Primary outcome measurePrimary efficacy:
Quality of life measured using KCCQ-OSS at 6 months

Primary mechanistic:
CFR measured using pressure wire at 6 months
Secondary outcome measuresSecondary outcomes:
1. All-cause death and hospitalisation for heart failure at 6 months
2. Efficacy of blinding assessed using standard tools at discharge
3. ICHOM standard outcome set for heart failure at 6 months
4. Individual components of the KCCQ (including total symptom score and clinical summary score) at 6 months
5. Health status measured using New York Heart Association (NYHA) functional class at 6 months
6. NT-pro-BNP measured using blood test/assay at 6 months
7. Difference in left ventricular ejection fraction (LVEF) and diastolic function (mitral E/e’) measured at 6 months

Secondary mechanistic:
Change in invasively measured fractional flow reserve (FFR), CFR and microvascular resistance from pre- to post-PCI in all target coronary arteries measured during the PCI procedure
Overall study start date01/09/2024
Completion date31/08/2029

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsPlanned Sample Size: 350; UK Sample Size: 350
Key inclusion criteria1. A diagnosis of HFpEF, defined by the European Society of Cardiology (ESC) criteria, as:
1.1. Symptoms of heart failure (New York Heart Association (NYHA) class II-IV)
and
1.2. Left ventricular ejection fraction >=50%
and
1.3. One or more of the following objective signs of left ventricular diastolic dysfunction:
1.3.1. Invasively measured left ventricular end diastolic pressure >=15 mmHg at rest or >=25 mmHg on exercise (directly measured or estimated via pulmonary capillary wedge pressure)
1.3.2. Estimated pulmonary artery systolic pressure > 35mmHg or tricuspid regurgitation velocity >2.8 m/s on echocardiography
1.3.3. Left atrial volume index >34ml/m2 in patient in sinus rhythm or left atrial volume index >40 ml/m2 in atrial fibrillation
1.3.4. Relative left ventricular wall thickness >0.42
1.3.5. Left ventricular mass index >=95 g/m2 in females or >=115 g/m2 in males
1.3.6. Mitral E/E’ ratio > 9
and
1.4. NT-pro-BNP >125 pg/ml in sinus rhythm or >365 pg/ml in atrial fibrillation

plus

2. Significant coronary artery disease defined as:
2.1. Functionally significant disease in at least one major proximal epicardial coronary artery (British Cardiovascular Intervention Society Jeopardy Score >=4) with a fractional flow reserve (FFR) <=0.80 measured with FFR, estimated with computational fluid dynamics during invasive angiography (e.g. VFR) or CT-FFR.
Key exclusion criteria1. Age <18 years
2. People without capacity to provide informed consent
3. PCI contraindicated or not feasible on coronary angiography or screening CTCA
4. Contraindication to clopidogrel/dual antiplatelet therapy
5. Recent acute myocardial infarction or coronary revascularisation (within 90 days)
6. Enrolment in another interventional study which may affect study outcomes
7. Severe chronic obstructive pulmonary disease (GOLD stage >=3)
8. Haemoglobin <=80 g/L
9. Other cardiac diagnosis as a cause for HFpEF (hypertrophic cardiomyopathy, untreated severe left sided valvular disease, cardiac amyloidosis)
Date of first enrolment01/09/2025
Date of final enrolment31/05/2028

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centres

St Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
Poole Hospital
Longfleet Road
Poole
BH15 2JB
United Kingdom
Mid and South Essex NHS Foundation Trust
Prittlewell Chase
Westcliff-on-sea
SS0 0RY
United Kingdom

Sponsor information

King's College London
Hospital/treatment centre

Room 8.11, 8th Floor Melbourne House
44-46 Aldwych
London
WC2B 4LL
England
United Kingdom

Phone +44 (0)2078487306
Email vpri@kcl.ac.uk
Website https://www.kcl.ac.uk/index
ROR logo "ROR" https://ror.org/0220mzb33
Guy's & St Thomas' NHS Foundation Trust
Hospital/treatment centre

R&D Department 16th Floor
Tower Wing
Great Maze Pond
London
SE1 9RT
England
United Kingdom

Phone +44 (0)20 7188 7188 Ext: 54426
Email gstt.RandD@nhs.net

Funders

Funder type

Government

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes:

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planResults of the study will be disseminated in peer-reviewed scientific journals and presented at major international scientific conferences. Participants will be invited to attend a dedicated trial results webinar or provided a summary of the results in lay language. Publication of the study results is expected in summer 2029.
IPD sharing planThe data sharing plans for the current study are unknown and will be made available at a later date

Editorial Notes

02/05/2025: Study's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).