Coronary Artery Disease, Peripheral Arterial Disease
Conditions
Keywords
Platelets, optical aggregometry, Lower Limb disease
Brief summary
After an episode of acute ischemic syndrome, patients with concomitant peripheral arterial disease have a worse short- and long-term prognosis compared to patients with isolated coronary disease, but the mechanisms responsible are poorly understood. In this population, the presence of high platelet aggregability despite the use of antiplatelet drugs is related to a greater risk of future complications, including heart attack and death from all causes. Thus, the main objective of the present project is to evaluate the role of platelet aggregability, analyzed by optical aggregometry using the AggRAM® equipment, in patients with a history of previous acute myocardial infarction with and without the presence of peripheral arterial disease. Among the secondary objectives, it is worth analyzing platelet aggregability, in both groups, using the Plateletworks® method. This is a case-control study, with groups differentiated by the presence or absence of peripheral arterial disease, matched by sex and age. It is expected that, in the end, relevant aspects related to platelet aggregation will be better characterized in this high cardiovascular risk population, with a likely impact on new therapeutic strategies that can positively influence the morbidity and mortality of these patients.
Detailed description
Polyvascular involvement is frequently present in atherosclerotic disease (AD). Lower Extremity Peripheral Artery Disease (PAD) represents one of the manifestations of AD; it is estimated that around 47% of people with atherosclerotic disease have involvement in more than one vascular bed, with coronary atherosclerotic disease and lower limb AD being the most prevalent. Initial studies suggest that platelet aggregability is increased in patients with PAD and the level of platelet aggregability is associated with the severity of PAD.However, to our knowledge, there are no studies in the literature analyzing platelet aggregability in patients with previous AMI with and without the concomitant presence of PAD, which is the proposal of this research project. This study is an observational, case-control study, matched by sex and age. Two groups will be selected: Patients with previous infarction and isolated coronary involvement (Group 1); Patients with previous AMI and concomitant presence of PAD of the lower limbs (Group 2). Primary objective is compare platelet aggregability analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratories) between the groups. Secondary objetives includes laboratorial test of inflammation, coagulation and subgroup analysis.
Interventions
DRUGClopidogrel
Clopidogrel 75 mg once a day for 14 days.
Sponsors
University of Sao Paulo
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women aged ≥ 18 years; 2. Daily use of AAS 81-100 mg and statins; 3. History of acute myocardial infarction, proven by medical record analysis; 4. Group 2 (patients with PAD): Ankle-Brachial Index number (ABI) ≤ 0.9 in at least one of the lower limbs. In diabetic patients with ABI \> 1.4, the Hallux-Brachialis Index should be performed if possible; if the patient presents a value \< 0.7, they can be included; 5. Signing of the Free and Informed Consent Form.
Exclusion criteria
1. Use of adenosine-diphosphate (ADP) receptor antagonists in the last 7 days before inclusion in the study; 2. Use of Anticoagulants in the last 30 days before inclusion in the study; 3. Clopidogrel allergy; 4. Known atherosclerotic carotid disease or carotid bruit; 5. History of upper gastrointestinal bleeding in the last 12 months; 6. Pregnancy or lactation; 7. Known platelet dysfunction or platelet count \<100,000/µL or \>450,000/µL; 8. Known liver disease or coagulation disorder; 9. Hematocrit less than 34% or greater than 55%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aggregability analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratories) | 14 days | Compare platelet aggregability analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratórios) between both groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum levels of Lipoprotein(a) (LPa) | Baseline | Evaluation of Serum levels of Lipoprotein(a) (LPa) |
| Mean platelet volume (MPV); | Baseline | Evaluation of Mean platelet volume (MPV); |
| Serum levels of P-Selectin ; | Baseline | Evaluation of Serum levels of P-Selectin ; |
| Serum levels of ultrasensitive C-reactive protein (hs-CRP); | Baseline | Avaliation of Serum levels of ultrasensitive C-reactive protein (hs-CRP) |
| Platelet aggregability by AggRAM™ arachidonic acid at baseline; | Baseline | Avaliation of Platelet aggregability by AggRAM™ arachidonic acid at baseline; |
| Platelet aggregability by AggRAM™ ADP after 14 days of use of Clopidogrel 75 mg/day; | 14 days | Evaluation of Platelet aggregability by AggRAM™ ADP after 14 days of use of Clopidogrel 75 mg/day; |
| Platelet aggregability by Plateletworks-ADP at baseline and after 14 days of use of Clopidogrel 75 mg/day; | 14 days | Evaluation of Platelet aggregability by Plateletworks-ADP at baseline and after 14 days of use of Clopidogrel 75 mg/day; |
| Serum levels of type I plasminogen activator inhibitor (PAI 1); | Baseline | Evaluation of Serum levels of type I plasminogen activator inhibitor (PAI 1); |
| Serum levels of interleukin 6; | Baseline | Evaluation of Serum levels of interleukin 6; |
| Serum levels of Interleukin 1 | Baseline | Evaluation of Serum levels of Interleukin 1 |
| Serum levels of cholesterol ester transfer proteins; | Baseline | Evaluation of Serum levels of cholesterol ester transfer proteins; |
| Serum levels of immature platelets; | Baseline | Evaluation of Serum levels of immature platelets; |
| Platelet count; | Baseline | Evaluation of Platelet count; |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subgroup Analysis- Age | Baseline and 14 days | Age (≥65 years or \< 65 years) |
| Subgroup Analysis- hypertension | Baseline and 14 days | History of arterial hypertension (presence or not); |
| Subgroup Analysis- BDI | Baseline and 14 days | Body Mass Index (\<30 or ≥ 30 kg/m2); |
| Subgroup Analysis- Diabetes mellitus | Baseline and 14 days | Diabetes mellitus (presence or not); |
| Subgroup Analysis-Glomerular filtration rate | Baseline and 14 days | Glomerular filtration rate (CKD EPI) (\< 60ml/min/m2 or ≥ 60 ml/min/m2); |
| Subgroup Analysis- Smoking | Baseline and 14 days | Current smoking (yes or no); |
| Subgroup Analysis- Ankle-brachial index number | Baseline and 14 days | ABI 0.41-0.90 (mild/moderate) or \<0.41 (Severe) or history of amputation. |
| Subgroup Analysis- Glycated hemoglobin | Baseline and 14 days | Glycated hemoglobin(more or less than 8%); |
| Subgroup Analysis- Use of proton pump inhibitor | Baseline and 14 days | Use of proton pump inhibitor (yes or no). |
| Subgroup Analysis- Sex | Baseline and 14 days | Sex (male/female) |
Countries
Brazil
Outcome results
None listed