Effect of Long-term Exercise on Haemostasis and Inflammation in Patients With Coronary Artery Disease

Study Overview
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Brief Summary
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Introduction: Regular exercise training improves prognosis in patients with coronary artery disease (CAD). This study investigates whether the beneficial effects of exercise can be partly explained by favourable changes in haemostasis and inflammation. Methods: 150 CAD patients are randomised to a supervised long-term exercise program (3 months) or usual care. Blood samples are obtained at baseline, 1.5 months, and 3 months after randomisation. Results: The investigators will evaluate platelet turnover and aggregation, coagulation, fibrinolysis, and inflammatory markers before and after short- and long-term exercise, and the two randomised groups will be compared. Perspectives: The present study will increase our knowledge of the beneficial mechanisms underlying the effect of exercise in CAD patients, potentially paving the way for improved exercise recommendations.

Official Title
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Effect of Long-term Exercise on Haemostasis and Inflammation Compared With Standard Care in Patients With Stable Coronary Artery Disease: a Randomised Clinical Trial

Conditions
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Coronary Artery Disease, Exercise, Inflammation, Hemostasis

Intervention / Treatment
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* Other: Long-term exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Angiographically verified coronary artery disease with stenosis of at least 50% or previous percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG) surgery. Diagnosis or revascularisation have been made at least 12 months prior to inclusion. Exclusion Criteria: Inability to perform strenuous exercise Anticoagulant treatment Heart failure (ejection fraction <30% or NYHA >2) Implanted implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) Serious arrhythmia requiring hospitalisation within the last 6 months Severe valvular heart disease Chronic obstructive pulmonary disease GOLD IV

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Long-term exercise<br>Supervised exercise training three times a week for three months. | Other: Long-term exercise<br>* All patients randomised to long-term exercise will perform exercise training at least three times a week for three months. The exercise is supervised and individualised.<br>|
| No Intervention: Usual care<br>Patients are not offered supervised exercise. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fibrinolytic biomarkers: tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). | Changes in fibrinolytic biomarkers in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare fibrinolytic biomarkers assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in clot maximum absorbance using the clot lysis assay. | Changes in maximum absorbance in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare clot maximum absorbance assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in clot lysis time using the clot lysis assay. | Changes in clot lysis time in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare clot lysis time assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in area under the curve using the clot lysis assay. | Changes in area under the curve in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare area under the curve assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in platelet aggregation using arachidonic acid (ASPI) as agonist. | Changes in platelet aggregation with ASPI as agonist in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in platelet aggregation using adenosine diphosphate (ADP) as agonist. | Changes in platelet aggregation with ADP as agonist in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in platelet aggregation using thrombin receptor activating peptide-6 (TRAP) as agonist. | Changes in platelet aggregation with TRAP as agonist in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in thrombin generation assessing lag-time until initial thrombin generation. | Changes in lag-time until initial thrombin generation in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in thrombin generation assessing maximum concentration of thrombin. | Changes in maximum concentration of thrombin in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in thrombin generation assessing time to peak. | Changes in time to peak in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in thrombin generation assessing endogenous thrombin potential. | Changes in endogenous thrombin potential in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare the results assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in coagulation biomarkers: APTT, INR, Factor VIII, vWF. | Changes in coagulation biomarkers in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare coagulation biomarkers assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 
| Changes in inflammatory biomarkers: CRP, multiple interleukins, tumor necrosis factor alpha (TNF-α), interferon gamma (INF-γ) and more. | Changes in inflammatory biomarkers in coronary artery disease patients who are randomised to long-term exercise compared with patients randomised to usual care (control group). Moreover, the investigators will compare inflammatory biomarkers assessed at baseline and after three months of supervised exercise for every patient. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular Diseases, Exercise, Hemostasis, Inflammation