Clinical trial NCT06854302: Angina After PCI: a Systems Medicine Study
Official title: Angina After PCI: a Systems Medicine Cohort Study
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Angina (Stable)
Ischemic Heart Disease (IHD)
Keywords: Angina
Microvascular angina
Percutaneous coronary intervention
Systems medicine
Health economics
cohort study
coronary artery disease
Cardiovascular magnetic resonance imaging
Coronary physiology
Health-related quality of life
Clinical outcomes
Lead sponsor: NHS National Waiting Times Centre Board
Sponsor class: OTHER
Collaborators: name: Robertson Centre for Biostatistics - University of Glasgow
name: British Heart Foundation
name: Abbott Medical Devices
name: CoreAalst BV
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2025-03-03
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with stable angina in whom stress perfusion CMR imaging is reasonable on clinical and/or research grounds and in whom invasive management is plausible or intended will be eligible to participate.

Brief summary: Angina may persist or recur in patients treated by coronary angioplasty. The angioplasty involves a balloon treatment to open a blocked heart blood vessel and usually a stent (thin metal tube) is placed. Stents do not always improve symptoms and may make symptoms worse. Sometimes a drug-eluting-balloon is used instead of a stent.

This balloon coats the inside of the blood vessel to prevent re-narrowing. Research is needed to clarify the causes of ongoing angina and its impact on patients and the NHS, and to identify which patients will or will not benefit from a stent (hence avoiding over-treatment in the future).

We plan a 5-year UK-wide multicenter study involving up to 600 patients with angina undergoing coronary angioplasty (with or without a stent). They will initially have a heart MRI scan. We will assess what might influence the recurrence of angina in the year after the angioplasty procedure. We will measure small blood vessel function in the heart and the amount of plaque persisting after PCI.

Patients who report angina after coronary angioplasty usually have a second invasive angiogram. Instead, we will invite patients to have a heart MRI scan allowing us to also assess whether this scan might be more useful than a repeat angiogram in guiding clinical care. We will collaborate with life scientists, mathematicians, statisticians, and health economists to better understand causes and health economic implications of angina arising after coronary angioplasty procedures.

Detailed description: Background: Prior studies indicate that potentially one in three patients may experience angina within 12 months of undergoing percutaneous coronary intervention (PCI).

Hypothesis: 1) Diffuse coronary atherosclerosis and/or microvascular dysfunction impair myocardial blood flow (MBF) leading to angina post-PCI.

Design: A 5-year interdisciplinary program with 3 scientific work-packages (WPs): 1) Clinical, 2) Systems medicine, and 3) Health Economics.

WP1) Cohort study In 4 or more centers in the United Kingdom, 600 patients with angina will undergo stress/rest perfusion cardiovascular magnetic resonance (CMR) imaging with inline pixel-mapping of MBF (ml/min/g) and then coronary physiology measured during PCI. Patient reported outcome measures will be collected routinely during follow-up to 12 months.

Primary outcome: Adjudicated, residual angina (Seattle Angina Questionnaire Angina Frequency (SAQ-7-AF) score \<90).

Nested case-control study: stress perfusion CMR (MBF culprit artery territory, primary outcome) in approximately 200 patients reporting residual angina and 50 consecutive asymptomatic controls (all post-PCI). Clinically indicated coronary angiography including physiology tests (change from baseline measurement) and acetylcholine testing will be undertaken in approximately 120 patients.

WP2) Systems medicine (n=600) using biostatistics to identify multivariable baseline associates (clinical, coronary physiology, haemodynamics, circulating biomarkers (DNA, RNA, protein) of the SAQ-7-AF score (range 0 (Severe) - 100 (no angina)) post-PCI.

WP3) Health economics of NHS resource utilization and value of information (VoI) modelling to design stratified medicine trials.

Value: Identification of mechanisms to inform downstream diagnostic and therapeutic strategies for angina post-PCI.

Eligibility criteria: Inclusion Criteria:

BEFORE INVASIVE MANGEMENT

1. Angina by SAQ-7 Angina Frequency Score \<90\*
2. Stress CMR imaging\*

   DURING INVASIVE MANAGEMENT
3. PCI (successful)
4. Coronary physiology assessment post-PCI.

Exclusion Criteria:

1. Age \<=18 years
2. Acute MI within 30 days
3. Invasive management \>90 days after stress CMR
4. Inability to comply with the protocol
5. Lack of written informed consent.
6. Pregnancy.

Primary outcomes:
measure: Residual angina after percutaneous coronary intervention.
timeFrame: From enrolment to 12 months
Secondary outcomes:
measure: Angina
timeFrame: From enrolment to 12 months
measure: Myocardial perfusion reserve
timeFrame: From enrolment to 12 months
measure: Fractional flow reserve post-percutaneous coronary intervention
timeFrame: 24 hours
measure: Coronary flow reserve after percutaneous coronary intervention
timeFrame: 24 hours
measure: Index of microvascular resistance after percutaneous coronary intervention
timeFrame: 24 hours
measure: Microvascular dysfunction after percutaneous coronary intervention
timeFrame: 24 hours
measure: Health-related quality of life
timeFrame: From enrolment to 12 months
measure: Physical function
timeFrame: From enrolment to 12 months
measure: Illness perception
timeFrame: From enrolment to 12 months
measure: Anxiety and depression
timeFrame: From enrolment to 12 months
measure: Productivity loss
timeFrame: From enrolment to 12 months
measure: Fraility
timeFrame: From enrolment to 12 months
measure: Serious adverse events
timeFrame: From enrolment to 12 months
measure: Low density lipoprotein
timeFrame: From enrolment to 12 months
Other outcomes:
measure: Inflammation
timeFrame: From enrolment to 12 months
measure: Glycemic status
timeFrame: From enrolment to 12 months
measure: Myocardial injury
timeFrame: From enrolment to 12 months
measure: Lipoprotein(a)
timeFrame: From enrolment to 12 months
measure: Microvascular dysfunction (acetylcholine test population)
timeFrame: 24 hours
measure: Microvascular blood flow
timeFrame: From enrolment to 12 months
measure: Impaired myocardial blood flow
timeFrame: From enrolment to 12 months
measure: Coronary vasomotor dysfunction in response to intracoronary infusion of acetylcholine
timeFrame: From enrolment to 12 months
measure: Myocardial blood flow (hyperaemic, global)
timeFrame: From enrolment to 12 months
Locations:
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
state: Cambridgeshire
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital
state: Dunbartonshire
city: East Kilbride
country: United Kingdom
facility: University Hospital Hairmyres
state: Lanarkshire
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: Yorkshire
Study officials:
affiliation: University of Glasgow
name: Colin Berry, BSc MBChB PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Crea F, Bairey Merz CN, Beltrame JF, Berry C, Camici PG, Kaski JC, Ong P, Pepine CJ, Sechtem U, Shimokawa H. Mechanisms and diagnostic evaluation of persistent or recurrent angina following percutaneous coronary revascularization. Eur Heart J. 2019 Aug 1;40(29):2455-2462. doi: 10.1093/eurheartj/ehy857.