Physical Activity Intervention in ELderly Patients With Myocardial INfarction

Study Overview
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Brief Summary
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Elderly patients presenting with myocardial infarction (MI) are the highest risk population with the worst prognosis. No trial has ever been designed to optimize their outcome through a systematic improvement of their physical performance. Cardiac rehabilitation demonstrated to improve prognosis of patients after MI. However, real-life data shows that older patients are not referred to rehabilitation centers or they have low rate of attendance because of the high number of rehabilitation sessions and of logistic problems. So, data about effectiveness of rehabilitation programs in older MI patients is lacking. The Physical Activity Intervention for Elderly Patients with Reduced Physical Performance after acute coronary syndrome (HULK) pilot study (NCT03021044) enrolled older MI patients and it demonstrated the feasibility and effectiveness of an early, tailored and low-cost physical activity intervention in terms of physical performance assessed by Short Physical Performance Battery (SPPB) score, that is strongly related to prognosis. The HULK study was focused on exercise training and not powered for hard endpoints. If a multi-domain lifestyle intervention in an adequately powered study may further improve prognosis is unknown. Thus, the investigator's hypothesis for the PIpELINe trial is that an early, tailored and low-cost multi-domain lifestyle intervention may improve prognosis of older MI patients compared to health education alone. The primary outcome is a composite of 1-year cardiovascular death and hospital readmission for cardiovascular cause.

Detailed Description
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The PIpELINe trial will include older MI patients. All patients aged 65 years and older undergoing coronary angiography because of MI must be screened for eligibility. Patient's eligibility must be assessed after percutaneous revascularization of all lesions considered susceptible of treatment. After verifying inclusion and exclusion criteria and after eligibility is confirmed, written informed consent must be obtained prior to randomization. At the time of the discharge (T0) SPPB test will be performed; in case of a score between 4 and 9, the patient will be evaluated 1-month after discharge at the inclusion visit (T1). If SPPB value is confirmed to be between 4 and 9, randomization will be performed. Key baseline patient characteristics (i.e., inclusion/exclusion criteria, demographics, medical history, details of cardiovascular anatomy and of revascularization, ECG and laboratory test results, echocardiographic data during the index hospitalization) will be recorded on the electronic Case Report Forms (eCRF). All angiographic and echocardiographic data will be collected and forwarded to a core lab for further assessment. Randomization will be performed during the inclusion visit (T1), 30 days after discharge. Randomization will be performed centrally using an internet-based system. The patient identification number (Patient ID) and the treatment allocation will be assigned by the central randomization system. Patients will be randomized to physical activity group or health education group by a 2:1 allocation. Treatment allocation will be assigned according to a computer-generated randomization list stratified by center. All randomized patients are irrevocably in the study, whether or not they are subsequently found to be eligible, or actually receiving the allocated treatment. Therefore, all patients must be followed until the pre-specified study end date. The aim of the study is to demonstrate that the proposed multi-domain lifestyle intervention reduces the composite endpoint of cardiovascular death and hospital readmission for cardiovascular cause. The primary endpoint is at 1 year. The follow-up will be extended up to 2 and 3 years. The protocol includes 3 pre-specified substudies. The possibility to participate in the substudy is left to patient's decision and doesn't preclude the procedures of the main protocol. Anxiety and depression: previous studies reported an association between cardiovascular events and a subsequent appearance of mood disorders which could determine a lack in following secondary prevention recommendations. No data is available about these disorders in older adults. In order to assess depression after MI in older patients and the effect of physical activity intervention on mood disorders, this sub-study will be performed. Mitochondrial function: in both study groups the mitochondrial functional are investigated starting from blood samples and skin biopsy. Skin biopsy is performed to obtain fibroblasts. In-vitro assessment of the mitochondrial function is done on the fibroblasts of patients. The parameters obtained are related with the effectiveness of physical intervention and with the benefit obtained. A total of at least 30 patients is required. Lymphocyte and miRNA activity: taking into account the immunosenescence and the benefits of physical activity on the immune system, this sub-study aims to obtain data regarding T-lymphocyte function in older adults and to assess the effect of physical activity intervention on the function of the different groups of T-lymphocyte. Analyses of physical activity effects on micro ribonucleic acids (miRNAs) are also performed.

Official Title
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Effectiveness of an Early, Tailored, Physical Activity Intervention in ELderly Patients With Myocardial INfarction: the PIpELINe Randomized Clinical Trial

Conditions
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Myocardial Infarction, Aging

Intervention / Treatment
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* Other: Health Education
* Other: Multi-domain lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥65 years Hospital admission for myocardial infarction Invasive management during index hospitalization including coronary artery angiography (± percutaneous coronary revascularization) SPPB value 4-9 at 1-month visit after hospital discharge Informed consent Exclusion Criteria: Multivessel coronary artery disease or left main coronary artery disease candidate to surgical revascularization Planned staged percutaneous coronary intervention (PCI) Non-cardiovascular co-morbidity reducing life expectancy to < 1 year Any factor precluding 1-year follow-up Severe aortic or mitral disease Ejection fraction <30% Chronic heart failure New York Heart Association (NYHA) III-IV Severe cognitive impairment (SPMSQ <4) Impossibility to do physical activity due to physical impairment

Ages Eligible for Study
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Minimum Age: 65 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Health Education<br>All patients randomized to health education during the inclusion visit are managed according to current guidelines and as follows. Quality of life, functional capacity and home physical activity are assessed by proper tools. | Other: Health Education<br>* Current gold standard in older patients admitted to hospital for MI. The group will receive a 20-minute session with one of the study physicians. Both the patient and relatives will attend these sessions. The study physician will stress the major issues related to a heart-healthy lifestyle and will explain the importance of PA as a powerful and independent factor to improve cardiovascular health and minimize cardiovascular risk. A detailed brochure explaining the benefits of physical activity will be provided to all patients<br>|
| Experimental: Multi-domain lifestyle intervention<br>All patients randomized to experimental arm will receive diet counselling, aggressive control of CV risk factors, smoke cessation program and exercise training. The physical activity (PA) intervention will start the program with a supervised PA session immediately after the inclusion visit. Quality of life, functional capacity and daily activities will be assessed by proper tools. The program provides 6 supervised PA sessions (30, 60, 90, 180, 270 and 360 days after hospital discharge [T0]). At the end of each supervised session, calisthenics exercises derived from Otago Exercise Program are prescribed. | Other: Multi-domain lifestyle intervention<br>* The intervention includes diet counselling, smoke cessation program, aggressive CV risk control and PA intervention. The PA intervention consisted of supervised sessions combined with an individualized home-based PA program. Centre-based sessions will be supervised by a sports physician and a nurse, and will take approximately 30 to 40 minutes, including a moderate standardized treadmill-walk, and strength and balance exercises. Based on the practice sessions, patients will receive a walking program to perform at home, unsupervised. The PA programs will be individualized, and consistent with current international recommendations. A selection of calisthenic exercises will be prescribed. Participants will be encouraged to perform the exercises three times per week (approximately 20 minutes). Adjustment of the type and intensity of the home-based PA regimen will be made at each visit. The PA program will be extensively described to the patient and family members.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative occurrence of cardiovascular death and hospital readmission for cardiovascular cause | To assess the superiority of the early and tailored physical activity intervention over health education alone in terms of 1-year composite endpoint of cardiovascular death plus hospital readmission for cardiovascular cause. | 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative occurrence of all-cause death | To test the superiority of the early and tailored physical activity intervention over the health education alone in terms of all-cause death | 1-year | 
| Cumulative occurrence of cardiovascular death | To test the superiority of the early and tailored physical activity intervention over the health education alone in terms of all-cause death | 1-year | 
| Cumulative occurrence of all-cause death | To test the superiority of the early and tailored physical activity intervention over the health education alone in terms of all-cause death | 3-year | 
| Cumulative occurrence of cardiovascular death | To test the superiority of the early and tailored physical activity intervention over the health education alone in terms of all-cause death | 3-year | 
| Cumulative occurrence of hospital readmission for cardiovascular cause | To assess the superiority of the early and tailored physical activity intervention over health education alone in terms of composite endpoint of cardiovascular death plus hospital readmission for cardiovascular cause. | 1-year | 
| Cumulative occurrence of hospital readmission for cardiovascular cause | To assess the superiority of the early and tailored physical activity intervention over health education alone in terms of composite endpoint of cardiovascular death plus hospital readmission for cardiovascular cause. | 3-year | 
| Cumulative occurrence of cardiovascular death and hospital readmission for cardiovascular cause | To assess the superiority of the early and tailored physical activity intervention over health education alone in terms of composite endpoint of cardiovascular death plus hospital readmission for cardiovascular cause. | 3-year |