Evaluation of Platelet Aggregability in Patients With Previous Acute Myocardial Infarction or Concomitant Lower Extremity Peripheral Artery Disease

Coronary Artery Disease Clinical Trial

Official title:

Evaluation of Platelet Aggregability in Patients With Previous Acute Myocardial Infarction or Concomitant Lower Extremity Peripheral Artery Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06454045
• Other study ID #: SDC: 5794/24/005
• Status: Active, not recruiting
• Start date: May 13, 2024
• Est. completion date: May 13, 2028

Study information

• Verified date: June 2024
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: May 13, 2028
• Est. primary completion date: May 13, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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%

Related Conditions & MeSH terms

• Coronary Artery Disease
• Infarction
• Myocardial Infarction
• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• Clopidogrel
Clopidogrel 75 mg once a day for 14 days.

Locations

Country	Name	City	State
Brazil	Heart Institute (InCor) / University of São Paulo	São Paulo	Sao Paulo

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (19)

Akahori H, Masuyama T, Imanaka T, Nakao K, Ozaki Y, Kimura K, Ako J, Noguchi T, Suwa S, Fujimoto K, Nakama Y, Morita T, Shimizu W, Saito Y, Hirohata A, Morita Y, Inoue T, Okamura A, Mano T, Hirata K, Tanabe K, Shibata Y, Owa M, Tsujita K, Funayama H, Kokubu N, Kozuma K, Uemura S, Tobaru T, Saku K, Oshima S, Nishimura K, Miyamoto Y, Ogawa H, Ishihara M; J-MINUET investigators. Impact of peripheral artery disease on prognosis after myocardial infarction: The J-MINUET study. J Cardiol. 2020 Oct;76(4):402-406. doi: 10.1016/j.jjcc.2020.05.014. Epub 2020 Jun 9. — View Citation

Andersen P, Kragholm K, Torp-Pedersen C, Jensen SE, Attar R. The impact of peripheral artery disease on major adverse cardiovascular events following myocardial infarction. Int J Cardiol. 2021 Nov 15;343:131-137. doi: 10.1016/j.ijcard.2021.08.053. Epub 2021 Sep 6. — View Citation

Attar R, Wester A, Koul S, Eggert S, Andell P. Peripheral artery disease and outcomes in patients with acute myocardial infarction. Open Heart. 2019 May 12;6(1):e001004. doi: 10.1136/openhrt-2018-001004. eCollection 2019. — View Citation

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. — View Citation

Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, Rensing BJ, Suttorp MJ, Hackeng CM, ten Berg JM. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010 Feb 24;303(8):754-62. doi: 10.1001/jama.2010.181. Erratum In: JAMA. 2010 Apr 7;303(13):1257. JAMA. 2011 Jun 1;305(21):2174. JAMA. 2011 Jun 1;305(21):2172-3. — View Citation

Cassar K, Bachoo P, Ford I, Greaves M, Brittenden J. Platelet activation is increased in peripheral arterial disease. J Vasc Surg. 2003 Jul;38(1):99-103. doi: 10.1016/s0741-5214(03)00129-0. — View Citation

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. — View Citation

Galt SW, McDaniel MD, Ault KA, Mitchell J, Cronenwett JL. Flow cytometric assessment of platelet function in patients with peripheral arterial occlusive disease. J Vasc Surg. 1991 Dec;14(6):747-55; discussion 755-6. doi: 10.1067/mva.1991.33419. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Patel MR, Becker RC, Wojdyla DM, Emanuelsson H, Hiatt WR, Horrow J, Husted S, Mahaffey KW, Steg PG, Storey RF, Wallentin L, James SK. Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared with clopidogrel: Data from the PLATO Trial. Eur J Prev Cardiol. 2015 Jun;22(6):734-42. doi: 10.1177/2047487314533215. Epub 2014 May 15. — View Citation

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. — View Citation

Rajagopalan S, Mckay I, Ford I, Bachoo P, Greaves M, Brittenden J. Platelet activation increases with the severity of peripheral arterial disease: implications for clinical management. J Vasc Surg. 2007 Sep;46(3):485-90. doi: 10.1016/j.jvs.2007.05.039. — View Citation

Robless PA, Okonko D, Lintott P, Mansfield AO, Mikhailidis DP, Stansby GP. Increased platelet aggregation and activation in peripheral arterial disease. Eur J Vasc Endovasc Surg. 2003 Jan;25(1):16-22. doi: 10.1053/ejvs.2002.1794. — View Citation

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. — View Citation

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. — View Citation

Thune JJ, Signorovitch JE, Kober L, McMurray JJ, Swedberg K, Rouleau J, Maggioni A, Velazquez E, Califf R, Pfeffer MA, Solomon SD. Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction. Eur J Heart Fail. 2011 Feb;13(2):148-53. doi: 10.1093/eurjhf/hfq194. Epub 2010 Oct 29. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subgroup Analysis- Sex	Sex (male/female)	Baseline and 14 days
Other	Subgroup Analysis- Age	Age (=65 years or < 65 years)	Baseline and 14 days
Other	Subgroup Analysis- hypertension	History of arterial hypertension (presence or not);	Baseline and 14 days
Other	Subgroup Analysis- BDI	Body Mass Index (<30 or = 30 kg/m2);	Baseline and 14 days
Other	Subgroup Analysis- Diabetes mellitus	Diabetes mellitus (presence or not);	Baseline and 14 days
Other	Subgroup Analysis-Glomerular filtration rate	Glomerular filtration rate (CKD EPI) (< 60ml/min/m2 or = 60 ml/min/m2);	Baseline and 14 days
Other	Subgroup Analysis- Smoking	Current smoking (yes or no);	Baseline and 14 days
Other	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
Other	Subgroup Analysis- Glycated hemoglobin	Glycated hemoglobin(more or less than 8%);	Baseline and 14 days
Other	Subgroup Analysis- Use of proton pump inhibitor	Use of proton pump inhibitor (yes or no).	Baseline and 14 days
Primary	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
Secondary	Platelet aggregability by AggRAM™ arachidonic acid at baseline;	Avaliation of Platelet aggregability by AggRAM™ arachidonic acid at baseline;	Baseline
Secondary	Platelet aggregability by AggRAM™ ADP after 14 days of use of Clopidogrel 75 mg/day;	Evaluation of Platelet aggregability by AggRAM™ ADP after 14 days of use of Clopidogrel 75 mg/day;	14 days
Secondary	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
Secondary	Serum levels of ultrasensitive C-reactive protein (hs-CRP);	Avaliation of Serum levels of ultrasensitive C-reactive protein (hs-CRP)	Baseline
Secondary	Serum levels of immature platelets;	Evaluation of Serum levels of immature platelets;	Baseline
Secondary	Platelet count;	Evaluation of Platelet count;	Baseline
Secondary	Mean platelet volume (MPV);	Evaluation of Mean platelet volume (MPV);	Baseline
Secondary	Serum levels of P-Selectin ;	Evaluation of Serum levels of P-Selectin ;	Baseline
Secondary	Serum levels of type I plasminogen activator inhibitor (PAI 1);	Evaluation of Serum levels of type I plasminogen activator inhibitor (PAI 1);	Baseline
Secondary	Serum levels of interleukin 6;	Evaluation of Serum levels of interleukin 6;	Baseline
Secondary	Serum levels of Interleukin 1	Evaluation of Serum levels of Interleukin 1	Baseline
Secondary	Serum levels of cholesterol ester transfer proteins;	Evaluation of Serum levels of cholesterol ester transfer proteins;	Baseline
Secondary	Serum levels of Lipoprotein(a) (LPa)	Evaluation of Serum levels of Lipoprotein(a) (LPa)	Baseline