Angina Patients With Non-obstructive Coronary Artery Disease
Conditions
Keywords
Angina, Women, Resistance exercise, Cardiovascular disease, Clinical trial
Brief summary
Angina is a feeling of chest pain or discomfort which can happen if there is reduced blood flow to the heart. Patients can experience angina with no obstructive coronary arteries (ANOCA) which is a difficult condition to treat (ie relieve angina) since few randomised, controlled therapy trials have been undertaken for ANOCA. Until now, angina has been mainly studied in men even though women are at least two-fold more likely than men to experience ANOCA. In 2023, a Scientific Statement from the American Heart Association affirmed that resistance exercise training can improve or maintain muscle mass and strength and confer favourable physiological and clinical effects on cardiovascular disease and risk factors. Resistance exercise has not been assessed in ANOCA and it offers an important opportunity to study non drug alternatives to treatment for women. This study will use a resistance based exercise programme to investigate if symptoms of ANOCA can be improved in women. It will recruit at least 76 patients (maximum 152 patients) across 13 hospitals in the UK and the Netherlands. The study will use a randomised wait list control design. This means all participants will be offered the intervention, but the randomisation will decide when they undergo it. It is part of a platform of trials for women with ANOCA. We are also setting up a drug study called ANOCA Therapy and a cohort study called ANOCA- Diagnosis.
Detailed description
There is a gap in knowledge on evidence-based therapy for ANOCA. Stratified medicine is a population-level diagnostic approach for identifying endotypes in a heterogenous population of all-comers. An endotype is defined as a subtype of a condition, which must be characterised by a distinct functional or pathophysiological mechanism. Use of quantitative noninvasive and invasive diagnostic methods, such as magnetic resonance imaging and coronary function tests involving acetylcholine testing, enables more accurate identification and discrimination of causal endotypes of ANOCA. This is especially relevant for women with ANOCA who have historically been under-recognised. Quantitative diagnostic methods should bring an end to empirical therapy, therapeutic nihilism and sex disparities in ANOCA. Precision medicine is different. Precision medicine targets the individual (and their endotype) with a mechanism informed therapy. Accordingly, in this Wellcome Leap Visible project, we will employ a stratified medicine diagnostic approach in women with suspected ANOCA undergoing invasive CFTs in multiple hospitals and then employ a precision medicine strategy by offering each woman an endotype-informed therapy option. Resistance exercise has not been previously investigated in ANOCA and it therefore represents a novel therapeutic option. This lifestyle intervention will increase the range of trial options, maximize patient choice for participation, and facilitate timely delivery of this project. The beneficial effects of resistance exercise on cardiovascular function have recently been endorsed in a Scientific Statement from the American Heart Association and further supported by a systematic review and favourable experience in our recent randomized trial in Long COVID. In 2023, a Scientific Statement from the American Heart Association affirmed that resistance exercise training can improve or maintain muscle mass and strength and confer favourable physiological and clinical effects on cardiovascular disease and risk factors. In 19 men with coronary artery disease and endothelial dysfunction, indicated by abnormal acetylcholine-induced coronary vasoconstriction, a randomized controlled trial of aerobic exercise training demonstrated improvements in endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels. The intervention involved an exercise program six times per day for at least 10 minutes. These results were promising but came with major limitations: no women were included in the study and the exercise program is both burdensome and impractical. Resistance exercise has not been assessed in ANOCA. Inclusion of a non-CTIMP (lifestyle intervention) brings strategic advantages to our ANOCA platform. A non-medicinal intervention provides an accessible therapy option for women of child-bearing age and for those who may prefer not to participate in an investigational drug trial. This non-CTIMP may also become an option for women who withdraw from a CTIMP, or who complete a CTIMP and are willing to continue into a second trial. The basket trial of resistance exercise may include participants who have completed a precision medicine CTIMP who then wish to participate in the resistance exercise trial or vice versa.
Interventions
BEHAVIORALResistance based exercise
Participants will undergo daily resistance based exercise for 8 weeks
Sponsors
NHS Greater Glasgow and Clyde
The University of Glasgow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomised, open-label, parallel group, waiting list controlled clinical trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Angina with no obstructive coronary arties (ANOCA) 2. Myocardial perfusion reserve or coronary flow reserve recorded within three years 3. Seattle Angina Questionnaire frequency score ≤60 4. Duke Activity Status Index ≤34 5. Female sex
Exclusion criteria
1. Age \<18 years 2. Unable to provide informed consent 3. \- Unable to comply with the protocol 4. Pregnancy 5. Currently undertaking resistance exercise activities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seattle Angina Questionnaire | Change from Baseline to Week 9 | The Seattle Angina Questionnaire a validated 19-item patient-reported survey used to measure coronary artery disease and angina treatment efficacy. Patients will complete on paper or electronically. The scores range from 0 to 100, with higher scores indicating less frequent angina, improved function, and better quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial perfusion reserve (MPR) | Change from baseline to week 9 | The ratio of maximum blood flow in the heart muscle under stress compared to resting flow |
| Handgrip strength using hand dynamometer | Change from baseline to week 9 | Measured in Kgs. This is used as a proxy for overall body strength with lower measures indicating less strength. |
| Short Physical Performance Battery (SPPB) | Change from baseline to week 9 | Used as a proxy for fitness |
| Brief Illness perception Questionnaire (Brief IPQ) | Change from baseline to week 9 | A nine-item scale designed to rapidly assess the cognitive and emotional representations of illness. It consists of 9 items: 8 are scored on a 0-10 scale, and item 9 is an open-ended question assessing perceived causes. The total score (0-80) is calculated by summing the first 8 items, with items 3, 4, and 7 reverse scored. Higher scores generally reflect a more threatening perception of the illness |
| Patient Health Questionnaire-4 of (PHQ4) | Change from Baseline to Week 9 | An ultra-brief screening tool used to assess core symptoms of anxiety and depression. Higher scores indicate greater feelings of anxiety and depression. |
| Duke Activity Status Index (DASI) | From Baseline to Week 9 | A 12-item, self-administered questionnaire used to estimate a patient's functional capacity and peak oxygen uptake. Scores range from 0 to 58.2, with higher scores indicating better physical fitness and lower risk |
| EQ-5D (EQ-5D-5L) | Change from Baseline to Week 9 | The EQ-5D evaluates health across 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). It yields three metrics: a 5-digit health profile string, a weighted index value, and a 0-100 self-rated Visual Analogue Scale (VAS) score. For the 5-digit health profile string higher individual numbers indicate worse health problems. For the weighted index value a score of 1 indicates perfect health, while 0 represents death. For the visual analogue score higher numbers here indicate better health |
| International Physical Activity Questionnaire (IPAQ) | Change from Baseline to Week 9 | Used to obtain comparable estimates of physical activity between populations and countries. Higher scores indicate greater physical activity. |
| Fatigue severity scale questionnaire | Change from Baseline to Week 9 | Rates level of fatigue. 9 statements assess how fatigue impacts daily life. Each statement is rated on a 7-point Likert scale, ranging from 1 (strongly disagree) to 7 (strongly agree). Higher scores indicate greater fatigue. |
| Short Form Post-Exercise Malaise Questionnaire | Change from Baseline to Week 9 | measures symptom exacerbation by assessing frequency and severity of symptoms. Higher scores reflect a stronger indication of post exercise malaise. |
| Episodes of care (primary, secondary, physiotherapy, rehabilitation) | Week 9 | How many times participants engaged with services |
| Hospitalisation for any reason by electronic health record review (where available) up to 4 months (Visit 3) | Week 17 | Review of medical notes to see if the patient has been in hospital |
Countries
United Kingdom
Contacts
CONTACTClare Dolan
CONTACTPMU Mail box
PRINCIPAL_INVESTIGATORColin Berry
The University of Glasgow
Outcome results
None listed