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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.
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 (AggRAMâ„¢- Helena Laboratories) between the groups. Secondary objetives includes laboratorial test of inflammation, coagulation and subgroup analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Isolated coronary involvement (Group 1) | Patients with previous infarction and isolated coronary involvement |
| |
| Concomitant presence of Lower Extremity Peripheral Artery Disease (Group 2) | Patients with previous AMI and concomitant presence of Lower Extremity Peripheral Artery Disease |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel | Drug | Clopidogrel 75 mg once a day for 14 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Aggregability analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratories) | Compare platelet aggregability analyzed by optical aggregometry-ADP (AggRAM™- Helena Laboratórios) between both groups | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Platelet aggregability by AggRAMâ„¢ arachidonic acid at baseline; | Avaliation of Platelet aggregability by AggRAMâ„¢ arachidonic acid at baseline; | Baseline |
| Platelet aggregability by AggRAMâ„¢ ADP after 14 days of use of Clopidogrel 75 mg/day; |
| Measure | Description | Time Frame |
|---|---|---|
| Subgroup Analysis- Sex | Sex (male/female) | Baseline and 14 days |
| Subgroup Analysis- Age | Age (≥65 years or < 65 years) | Baseline and 14 days |
Inclusion Criteria:
Exclusion Criteria:
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Group 1: Patients with previous infarction and isolated coronary involvement
Group 2: Patients with previous AMI and concomitant presence of Lower Extremity Peripheral Artery Disease.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Heart Institute (InCor) / University of São Paulo | São Paulo | São Paulo | 05403000 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34277248 | Background | Perez Mejias EL, Faxas SM, Taveras NT, Talpur AS, Kumar J, Khalid M, Aruwani SK, Khalid D, Khalid H, Memon S. Peripheral Artery Disease as a Risk Factor for Myocardial Infarction. Cureus. 2021 Jun 15;13(6):e15655. doi: 10.7759/cureus.15655. eCollection 2021 Jun. | |
| 11560536 | Background | Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, Krook SH, Hunninghake DB, Comerota AJ, Walsh ME, McDermott MM, Hiatt WR. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001 Sep 19;286(11):1317-24. doi: 10.1001/jama.286.11.1317. |
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Blood.
Evaluation of Platelet aggregability by AggRAMâ„¢ ADP after 14 days of use of Clopidogrel 75 mg/day;
| 14 days |
| Platelet aggregability by Plateletworks-ADP at baseline and after 14 days of use of Clopidogrel 75 mg/day; | Evaluation of Platelet aggregability by Plateletworks-ADP at baseline and after 14 days of use of Clopidogrel 75 mg/day; | 14 days |
| Serum levels of ultrasensitive C-reactive protein (hs-CRP); | Avaliation of Serum levels of ultrasensitive C-reactive protein (hs-CRP) | Baseline |
| Serum levels of immature platelets; | Evaluation of Serum levels of immature platelets; | Baseline |
| Platelet count; | Evaluation of Platelet count; | Baseline |
| Mean platelet volume (MPV); | Evaluation of Mean platelet volume (MPV); | Baseline |
| Serum levels of P-Selectin ; | Evaluation of Serum levels of P-Selectin ; | Baseline |
| Serum levels of type I plasminogen activator inhibitor (PAI 1); | Evaluation of Serum levels of type I plasminogen activator inhibitor (PAI 1); | Baseline |
| Serum levels of interleukin 6; | Evaluation of Serum levels of interleukin 6; | Baseline |
| Serum levels of Interleukin 1 | Evaluation of Serum levels of Interleukin 1 | Baseline |
| Serum levels of cholesterol ester transfer proteins; | Evaluation of Serum levels of cholesterol ester transfer proteins; | Baseline |
| Serum levels of Lipoprotein(a) (LPa) | Evaluation of Serum levels of Lipoprotein(a) (LPa) | Baseline |
| Subgroup Analysis- hypertension | History of arterial hypertension (presence or not); | Baseline and 14 days |
| Subgroup Analysis- BDI | Body Mass Index (<30 or ≥ 30 kg/m2); | Baseline and 14 days |
| Subgroup Analysis- Diabetes mellitus | Diabetes mellitus (presence or not); | Baseline and 14 days |
| Subgroup Analysis-Glomerular filtration rate | Glomerular filtration rate (CKD EPI) (< 60ml/min/m2 or ≥ 60 ml/min/m2); | Baseline and 14 days |
| Subgroup Analysis- Smoking | Current smoking (yes or no); | Baseline and 14 days |
| Subgroup Analysis- Ankle-brachial index number | ABI 0.41-0.90 (mild/moderate) or <0.41 (Severe) or history of amputation. | Baseline and 14 days |
| Subgroup Analysis- Glycated hemoglobin | Glycated hemoglobin(more or less than 8%); | Baseline and 14 days |
| Subgroup Analysis- Use of proton pump inhibitor | Use of proton pump inhibitor (yes or no). | Baseline and 14 days |
| 32099582 | Background | Bauersachs R, Zeymer U, Briere JB, Marre C, Bowrin K, Huelsebeck M. Burden of Coronary Artery Disease and Peripheral Artery Disease: A Literature Review. Cardiovasc Ther. 2019 Nov 26;2019:8295054. doi: 10.1155/2019/8295054. eCollection 2019. |
| 20805110 | Background | Fox KA, Carruthers KF, Dunbar DR, Graham C, Manning JR, De Raedt H, Buysschaert I, Lambrechts D, Van de Werf F. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian Study). Eur Heart J. 2010 Nov;31(22):2755-64. doi: 10.1093/eurheartj/ehq326. Epub 2010 Aug 30. |
| 26386792 | Background | Nicolau JC, Bhatt DL, Roe MT, Lokhnygina Y, Neely B, Corbalan R, Leiva-Pons JL, Martinez F, Goodman SG, Winters KJ, Verheugt FW, Armstrong PW, White HD, Fox KA, Prabhakaran D, Ohman EM; TRILOGY ACS investigators. Concomitant proton-pump inhibitor use, platelet activity, and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel and managed without revascularization: insights from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial. Am Heart J. 2015 Oct;170(4):683-694.e3. doi: 10.1016/j.ahj.2015.05.017. Epub 2015 Jun 11. |
| 34320090 | Background | Nicolau JC, Feitosa Filho GS, Petriz JL, Furtado RHM, Precoma DB, Lemke W, Lopes RD, Timerman A, Marin Neto JA, Bezerra Neto L, Gomes BFO, Santos ECL, Piegas LS, Soeiro AM, Negri AJA, Franci A, Markman Filho B, Baccaro BM, Montenegro CEL, Rochitte CE, Barbosa CJDG, Virgens CMBD, Stefanini E, Manenti ERF, Lima FG, Monteiro Junior FDC, Correa Filho H, Pena HPM, Pinto IMF, Falcao JLAA, Sena JP, Peixoto JM, Souza JA, Silva LSD, Maia LN, Ohe LN, Baracioli LM, Dallan LAO, Dallan LAP, Mattos LAPE, Bodanese LC, Ritt LEF, Canesin MF, Rivas MBDS, Franken M, Magalhaes MJG, Oliveira Junior MT, Filgueiras Filho NM, Dutra OP, Coelho OR, Leaes PE, Rossi PRF, Soares PR, Lemos Neto PA, Farsky PS, Cavalcanti RRC, Alves RJ, Kalil RAK, Esporcatte R, Marino RL, Giraldez RRCV, Meneghelo RS, Lima RSL, Ramos RF, Falcao SNDRS, Dalcoquio TF, Lemke VMG, Chalela WA, Mathias Junior W. Brazilian Society of Cardiology Guidelines on Unstable Angina and Acute Myocardial Infarction without ST-Segment Elevation - 2021. Arq Bras Cardiol. 2021 Jul;117(1):181-264. doi: 10.36660/abc.20210180. No abstract available. English, Portuguese. |
| 22740013 | Background | Smolina K, Wright FL, Rayner M, Goldacre MJ. Long-term survival and recurrence after acute myocardial infarction in England, 2004 to 2010. Circ Cardiovasc Qual Outcomes. 2012 Jul 1;5(4):532-40. doi: 10.1161/CIRCOUTCOMES.111.964700. Epub 2012 Jun 26. |
| 35475346 | Background | Steen DL, Khan I, Andrade K, Koumas A, Giugliano RP. Event Rates and Risk Factors for Recurrent Cardiovascular Events and Mortality in a Contemporary Post Acute Coronary Syndrome Population Representing 239 234 Patients During 2005 to 2018 in the United States. J Am Heart Assoc. 2022 May 3;11(9):e022198. doi: 10.1161/JAHA.121.022198. Epub 2022 Apr 27. |
| 23075765 | Background | Nakatani D, Sakata Y, Suna S, Usami M, Matsumoto S, Shimizu M, Sumitsuji S, Kawano S, Ueda Y, Hamasaki T, Sato H, Nanto S, Hori M, Komuro I; Osaka Acute Coronary Insufficiency Study (OACIS) Investigators. Incidence, predictors, and subsequent mortality risk of recurrent myocardial infarction in patients following discharge for acute myocardial infarction. Circ J. 2013;77(2):439-46. doi: 10.1253/circj.cj-11-1059. Epub 2012 Oct 17. |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D058729 | Peripheral Arterial Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D050197 | Atherosclerosis |
| D016491 | Peripheral Vascular Diseases |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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