Secondary Prevention of Cardiovascular Disease in the Elderly Trial

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of a polypill strategy containing aspirin (100 mg), ramipril (2.5, 5 or 10 mgs), and atorvastatin (40 mgs) compared with the standard of care (usual care according to the local clinical practices at each participating country) in secondary prevention of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and urgent revascularization) in elderly patients with a recent myocardial infarction.

Detailed Description
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A total number of 2499 patients have been randomized (1:1) to treatment arms. Patients will be recruited across seven countries in Europe (Spain, Italy, Germany, France, Hungary, Poland, and Czech Republic). Patients will be ≥65 years old and diagnosed with a type 1 myocardial infarction within 6 months prior to study enrolment. Once the inclusion and exclusion criteria are confirmed, patients will be included in the study after signing informed consent. Randomization will take place within 6 months of the index event (AMI type I) in a 1:1 ratio to one of the two arms: Cardiovascular Polypill (containing Aspirin, Ramipril, and Atorvastatin) Usual care Patients will be followed up for a minimum of 2 years and a maximum of 5 years. There will be 3 follow up visits at month 6, 12 and 24 and telephone follow up calls at month 18, 36, 48 and 60

Official Title
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Secondary Prevention of Cardiovascular Disease in the Elderly Trial

Conditions
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Myocardial Infarction, Cardiovascular Disease

Intervention / Treatment
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* Drug: Cardiovascular Polypill
* Drug: Treatment Prevention for Secondary CV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with a type 1 myocardial infarction within the previous 6 months. Subjects must be ≥65 years old, presenting with at least one of the following additional conditions: Documented diabetes mellitus or previous treatment with oral hypoglycemic drugs or insulin. Mild to moderate renal dysfunction: creatinine clearance 60-30 mL/min/1.73 m2. Prior myocardial infarction: defined as an AMI occurring before the index event documented in a medical report. Prior coronary revascularization: coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Prior stroke: history of a documented stroke, defined as an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of central nervous system tissue, not resulting in death. Age ≥ 75 years. Signing informed consent. Exclusion Criteria: Unable to sign informed consent. Contraindications to any of the components of the polypill. Living in a nursing home. Mental illness limiting the capacity of self-care. Participating in another clinical trial. Severe congestive heart failure (NYHA III-IV). Severe renal disease (Creatinine Clearance (CrCl) <30ml/min/1.73 m2). Need for oral anticoagulation at the time of randomization or planned in the future months. Any condition limiting life expectancy <2 years, including but not limited to active malignancy. Significant arrhythmias (including unresolved ventricular arrhythmias or atrial fibrillation). Scheduled coronary revascularization (patients can be randomized after final revascularization is completed within the prespecified timeframe). Do not agree to the filing, forwarding and use of his/ her pseudonymised data.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Prevention for Secondary CV<br>Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention according to the ESC guidelines. Drugs and doses will be left at the discretion of the treating physicians.. | Drug: Treatment Prevention for Secondary CV<br>* ESC Guideline (2013 guideline on management of stable coronary disease) recommended pharmacological treatment for event prevention.<br>* Other names: Renin-angiotensin-aldosterone system blockers;|
| Experimental: Cardiovascular Polypill<br>Patients allocated to the experimental arm will receive a cardiovascular polypill containing aspirin 100 mg, atorvastatin (40 or 20 mg) and ramipril (2.5, 5 or 10 mg) taken orally once a day. | Drug: Cardiovascular Polypill<br>* Cardiovascular Polypill contains Aspirin, Atorvastatin and Ramipril. Participants will receive one of the following cardiovascular polypill: (A) Aspirin 100 mg, Atorvastatin 40mg, and Ramipril (2.5 mg, or 5 mg, or 10mg). or (B) Aspirin 100 mg, Atorvastatin 20mg, and Ramipril (2.5 mg, or 5 mg, or 10mg).<br>* Other names: Polypill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the occurrence of Major Adverse Cardiovascular Events (MACE) between the Cardiovascular Combination Polypill AAR and the Standard of Care Treatment | Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of the first occurrence of any component of the following composite endpoint: CV death, MI, stroke. | Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization | Baseline | 
| Incidence of the first occurrence of any component of the following composite endpoint: CV death, MI, stroke. | Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization | 6 months after treatment initiation | 
| Incidence of the first occurrence of any component of the following composite endpoint: CV death, MI, stroke. | Cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent revascularization | 12 months after treatment initiation | 
| Evaluate the first occurrence of the individual components of the primary endpoint | CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization. | 18 months after treatment initiation | 
| Evaluate the first occurrence of the individual components of the primary endpoint | CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization. | 24 months after treatment initiation | 
| Evaluate the first occurrence of the individual components of the primary endpoint | CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization. | 36 months after treatment initiation | 
| Evaluate the first occurrence of the individual components of the primary endpoint | CV death. Nonfatal type 1 myocardial infarction. Nonfatal ischemic stroke. Urgent coronary revascularization. | 48 months after treatment initiation | 
| Change in Treatment Adherence | The Morisky-Medication Adherence Scale (8 item) Questionnaire will be administered | 6 months after patient treatment | 
| Change in Treatment Adherence | The Morisky-Medication Adherence Scale (8 item) Questionnaire will be administered | 24 months after patient treatment | 
| Change in Patient Satisfaction | The treatment Satisfaction Questionnaire for Medication (TSQM) will be administered | 6 months after patient treatment | 
| Change in Patient Satisfaction | The treatment Satisfaction Questionnaire for Medication (TSQM) will be administered | 24 months after patient treatment | 
| Change in Systolic and Diastolic Blood Pressure (SBP and DBP) | Systolic and diastolic blood pressure will be collected and summarized at each timepoint. | Baseline | 
| Change in Systolic and Diastolic Blood Pressure (SBP and DBP) | Systolic and diastolic blood pressure will be collected and summarized at each timepoint. | 6 months after patient treatment | 
| Change in Systolic and Diastolic Blood Pressure (SBP and DBP) | Systolic and diastolic blood pressure will be collected and summarized at each timepoint. | 12 months after patient treatment | 
| Change in Systolic and Diastolic Blood Pressure (SBP and DBP) | Systolic and diastolic blood pressure will be collected and summarized at each timepoint. | 24 months after patient treatment | 
| Change in LDL cholesterol level | Non-fasting blood analysis will be collected and LDL cholesterol level evaluated at each timepoint. | Baseline | 
| Change in LDL cholesterol level | Non-fasting blood analysis will be collected and LDL cholesterol level evaluated at each timepoint. | 12 months after patient treatment | 
| Change in LDL cholesterol level | Non-fasting blood analysis will be collected and LDL cholesterol level evaluated at each timepoint. | 24 months after patient treatment | 
| Regional differences in performance of the polypill in the previous endpoints | Assessed | 6 months after patient treatment | 
| Regional differences in performance of the polypill in the previous endpoints | Assessed | 12 months after patient treatment | 
| Regional differences in performance of the polypill in the previous endpoints | Assessed | 24 months after patient treatment | 
| Health Economic Evaluation Comparing Intervention and Usual Care Arm | Cost differences and Incremental Cost-Effectiveness Ratio (ICER) will be assessed at each timepoint. | 6 months after patient treatment | 
| Health Economic Evaluation Comparing Intervention and Usual Care Arm | Cost differences and Incremental Cost-Effectiveness Ratio (ICER) will be assessed at each timepoint. | 12 months after patient treatment | 
| Health Economic Evaluation Comparing Intervention and Usual Care Arm | Cost differences and Incremental Cost-Effectiveness Ratio (ICER) will be assessed at each timepoint. | 24 months after patient treatment | 
| Change in Quality of Life | The European Quality of Life- 5 Dimensions (EQ-5D) Questionnaire will be administered at each timepoint to evaluate change in quality of life. | Baseline | 
| Change in Quality of Life | The European Quality of Life- 5 Dimensions (EQ-5D) Questionnaire will be administered at each timepoint to evaluate change in quality of life. | 24 months after patient treatment | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation). | Baseline | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation). | 6 months after patient treatment | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation). | 12 months after patient treatment | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation). | 18 months after patient treatment | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation). | 24 months after patient treatment | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation). | 36 months after patient treatment | 
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | All-cause mortality and adverse events (bleeding, renal dysfunction, drug, allergies, and refractory cough leading to drug discontinuation). | 48 months after patient treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polypill, Prevention of Secondary Cardiovascular Disease, Cardiovascular Disease, Myocardial Infarction, Cardiovascular Combination Polypill AAR, Cardiovascular Disease in the Elderly, Adherence, SECURE, Elderly, Secondary Cardiovascular Disease, Secondary Cardiovascular Prevention, Randomized Cardiovascular Trial, Randomized Trial, Cardiovascular Polypill