Platelet Aggregation During Acute Myocardial Infarction Clinical Trial
Official title:
DPP-4 Inhibitors in Patients With Type 2 Diabetes and Acute Myocardial Infarction:Effects on Platelet Function
| Verified date | February 2020 |
| Source | University of Sao Paulo General Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Cardiovascular events are the main cause of mortality in diabetic patients ,on the other
hand,during an acute myocardial infarction(AMI),hyperglycemia increases mortality and is
related to different pathophysiologic processes.
More important evidence regarding the effect of glycemic control on AMI patients prognosis is
contradictory,and the potential benefits of dipeptidyl peptidase-4 inhibitors(DPP4-i) in this
setting is unknown.
The aim of this study is to assess the presence of pleiotropic effects of DPP4-i(sitagliptin
or saxagliptin) and their relationship with glycemic control during in-hospital phase of AMI.
| Status | Completed |
| Enrollment | 74 |
| Est. completion date | February 28, 2020 |
| Est. primary completion date | February 28, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - previous diagnosis of type 2 diabetes mellitus,with treatment including insulin and/or oral antidiabetic agent; - subjects without previous diagnosis of diabetes,but HbA1c admission >= 6,5% during current hospital-stay - AMI with or without ST-elevation; - use of double antiplatelet therapy; - signed informed consent term Exclusion Criteria: - GFR <30 ml/min; - use of DPP4 inhibitors or glucagon- like peptide-1(GLP1) analogue in the past 6 months; - use of strong inhibitors of cytochrome P450(CYP3A4/5) ou glucocorticoids; - severe systemic decompensation requiring insulin infusion; - Killip classification of myocardial infarction grade >2; - previous history of pancreatitis |
| Country | Name | City | State |
|---|---|---|---|
| Brazil | Heart Institute(InCor)-Acute Coronary Care Unit | São Paulo | SP |
| Lead Sponsor | Collaborator |
|---|---|
| University of Sao Paulo General Hospital | InCor Heart Institute |
Brazil,
Alzahrani SH, Ajjan RA. Coagulation and fibrinolysis in diabetes. Diab Vasc Dis Res. 2010 Oct;7(4):260-73. doi: 10.1177/1479164110383723. Epub 2010 Sep 16. Review. — View Citation
American Diabetes Association. Executive summary: Standards of medical care in diabetes--2012. Diabetes Care. 2012 Jan;35 Suppl 1:S4-S10. doi: 10.2337/dc12-s004. — View Citation
Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramírez C, Sabaté M, Jimenez-Quevedo P, Hernández R, Moreno R, Escaned J, Alfonso F, Bañuelos C, Costa MA, Bass TA, Macaya C. Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes. 2005 Aug;54(8):2430-5. — View Citation
Barnett AH, Charbonnel B, Donovan M, Fleming D, Chen R. Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin. 2012 Apr;28(4):513-23. doi: 10.1185/03007995.2012.665046. Epub 2012 Mar 1. — View Citation
Cobble ME, Frederich R. Saxagliptin for the treatment of type 2 diabetes mellitus: assessing cardiovascular data. Cardiovasc Diabetol. 2012 Jan 16;11:6. doi: 10.1186/1475-2840-11-6. Review. — View Citation
De Caterina R, Madonna R, Sourij H, Wascher T. Glycaemic control in acute coronary syndromes: prognostic value and therapeutic options. Eur Heart J. 2010 Jul;31(13):1557-64. doi: 10.1093/eurheartj/ehq162. Epub 2010 Jun 2. Review. — View Citation
de Mulder M, Umans VA, Cornel JH, van der Zant FM, Stam F, Oemrawsingh RM, Akkerhuis KM, Boersma E. Intensive glucose regulation in hyperglycemic acute coronary syndrome: results of the randomized BIOMarker study to identify the acute risk of a coronary syndrome-2 (BIOMArCS-2) glucose trial. JAMA Intern Med. 2013 Nov 11;173(20):1896-904. doi: 10.1001/jamainternmed.2013.10074. — View Citation
Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab. 2011 Jan;13(1):7-18. doi: 10.1111/j.1463-1326.2010.01306.x. Review. — View Citation
Demirtunc R, Duman D, Basar M, Bilgi M, Teomete M, Garip T. The relationship between glycemic control and platelet activity in type 2 diabetes mellitus. J Diabetes Complications. 2009 Mar-Apr;23(2):89-94. doi: 10.1016/j.jdiacomp.2008.01.006. Epub 2008 Mar 20. — View Citation
Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care. 2010 Jun;33(6):1389-94. doi: 10.2337/dc09-2082. Review. — View Citation
Engel SS, Round E, Golm GT, Kaufman KD, Goldstein BJ. Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies. Diabetes Ther. 2013 Jun;4(1):119-45. doi: 10.1007/s13300-013-0024-0. Epub 2013 May 23. Erratum in: Diabetes Ther. 2013 Dec;4(2):487. — View Citation
Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 2002 Oct 15;106(16):2067-72. — View Citation
Frederich R, Alexander JH, Fiedorek FT, Donovan M, Berglind N, Harris S, Chen R, Wolf R, Mahaffey KW. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med. 2010 May;122(3):16-27. doi: 10.3810/pgm.2010.05.2138. — View Citation
Goyal A, Mahaffey KW, Garg J, Nicolau JC, Hochman JS, Weaver WD, Theroux P, Oliveira GB, Todaro TG, Mojcik CF, Armstrong PW, Granger CB. Prognostic significance of the change in glucose level in the first 24 h after acute myocardial infarction: results from the CARDINAL study. Eur Heart J. 2006 Jun;27(11):1289-97. Epub 2006 Apr 12. — View Citation
Grant PJ. Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab. 2003 Sep;29(4 Pt 2):6S44-52. Review. — View Citation
Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR; TECOS Study Group. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015 Jul 16;373(3):232-42. doi: 10.1056/NEJMoa1501352. Epub 2015 Jun 8. Erratum in: N Engl J Med. 2015 Aug 6;373(6):586. — View Citation
Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, Dhaliwal R, Henderson WR, Chittock DR, Finfer S, Talmor D. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009 Apr 14;180(8):821-7. doi: 10.1503/cmaj.090206. Epub 2009 Mar 24. Review. — View Citation
Gupta AK, Verma AK, Kailashiya J, Singh SK, Kumar N. Sitagliptin: anti-platelet effect in diabetes and healthy volunteers. Platelets. 2012;23(8):565-70. doi: 10.3109/09537104.2012.721907. Epub 2012 Sep 5. — View Citation
Hermanides J, Vriesendorp TM, Bosman RJ, Zandstra DF, Hoekstra JB, Devries JH. Glucose variability is associated with intensive care unit mortality. Crit Care Med. 2010 Mar;38(3):838-42. doi: 10.1097/CCM.0b013e3181cc4be9. — View Citation
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012 Jun;35(6):1364-79. doi: 10.2337/dc12-0413. Epub 2012 Apr 19. Review. Erratum in: Diabetes Care. 2013 Feb;36(2):490. — View Citation
Jose T, Inzucchi SE. Cardiovascular effects of the DPP-4 inhibitors. Diab Vasc Dis Res. 2012 Apr;9(2):109-16. doi: 10.1177/1479164111436236. Epub 2012 Feb 15. Review. — View Citation
Karagiannis T, Paschos P, Paletas K, Matthews DR, Tsapas A. Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis. BMJ. 2012 Mar 12;344:e1369. doi: 10.1136/bmj.e1369. — View Citation
Khan S, Khan S, Imran M, Pillai KK, Akhtar M, Najmi AK. Effects of pioglitazone and vildagliptin on coagulation cascade in diabetes mellitus--targeting thrombogenesis. Expert Opin Ther Targets. 2013 Jun;17(6):627-39. doi: 10.1517/14728222.2013.764991. Epub 2013 Jan 28. Review. — View Citation
Kosiborod M, Inzucchi SE, Krumholz HM, Masoudi FA, Goyal A, Xiao L, Jones PG, Fiske S, Spertus JA. Glucose normalization and outcomes in patients with acute myocardial infarction. Arch Intern Med. 2009 Mar 9;169(5):438-46. doi: 10.1001/archinternmed.2008.593. — View Citation
Kosiborod M, Inzucchi SE, Krumholz HM, Xiao L, Jones PG, Fiske S, Masoudi FA, Marso SP, Spertus JA. Glucometrics in patients hospitalized with acute myocardial infarction: defining the optimal outcomes-based measure of risk. Circulation. 2008 Feb 26;117(8):1018-27. doi: 10.1161/CIRCULATIONAHA.107.740498. Epub 2008 Feb 11. — View Citation
Kosiborod M, Rathore SS, Inzucchi SE, Masoudi FA, Wang Y, Havranek EP, Krumholz HM. Admission glucose and mortality in elderly patients hospitalized with acute myocardial infarction: implications for patients with and without recognized diabetes. Circulation. 2005 Jun 14;111(23):3078-86. Epub 2005 Jun 6. — View Citation
Krinsley JS. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008 Nov;36(11):3008-13. doi: 10.1097/CCM.0b013e31818b38d2. — View Citation
Lamanna C, Monami M, Marchionni N, Mannucci E. Effect of metformin on cardiovascular events and mortality: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2011 Mar;13(3):221-8. doi: 10.1111/j.1463-1326.2010.01349.x. — View Citation
Lipska KJ, Venkitachalam L, Gosch K, Kovatchev B, Van den Berghe G, Meyfroidt G, Jones PG, Inzucchi SE, Spertus JA, DeVries JH, Kosiborod M. Glucose variability and mortality in patients hospitalized with acute myocardial infarction. Circ Cardiovasc Qual Outcomes. 2012 Jul 1;5(4):550-7. doi: 10.1161/CIRCOUTCOMES.111.963298. Epub 2012 Jun 12. — View Citation
Malmberg K, Rydén L, Efendic S, Herlitz J, Nicol P, Waldenström A, Wedel H, Welin L. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995 Jul;26(1):57-65. — View Citation
Malmberg K, Rydén L, Wedel H, Birkeland K, Bootsma A, Dickstein K, Efendic S, Fisher M, Hamsten A, Herlitz J, Hildebrandt P, MacLeod K, Laakso M, Torp-Pedersen C, Waldenström A; DIGAMI 2 Investigators. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J. 2005 Apr;26(7):650-61. Epub 2005 Feb 23. — View Citation
McGuire DK, Van de Werf F, Armstrong PW, Standl E, Koglin J, Green JB, Bethel MA, Cornel JH, Lopes RD, Halvorsen S, Ambrosio G, Buse JB, Josse RG, Lachin JM, Pencina MJ, Garg J, Lokhnygina Y, Holman RR, Peterson ED; Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS) Study Group. Association Between Sitagliptin Use and Heart Failure Hospitalization and Related Outcomes in Type 2 Diabetes Mellitus: Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016 May 1;1(2):126-35. doi: 10.1001/jamacardio.2016.0103. — View Citation
Monami M, Dicembrini I, Martelli D, Mannucci E. Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials. Curr Med Res Opin. 2011 Nov;27 Suppl 3:57-64. doi: 10.1185/03007995.2011.602964. — View Citation
Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006 Apr 12;295(14):1681-7. — View Citation
NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, Bellomo R, Cook D, Dodek P, Henderson WR, Hébert PC, Heritier S, Heyland DK, McArthur C, McDonald E, Mitchell I, Myburgh JA, Norton R, Potter J, Robinson BG, Ronco JJ. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009 Mar 26;360(13):1283-97. doi: 10.1056/NEJMoa0810625. Epub 2009 Mar 24. — View Citation
Nicolau JC, Maia LN, Vitola JV, Mahaffey KW, Machado MN, Ramires JA. Baseline glucose and left ventricular remodeling after acute myocardial infarction. J Diabetes Complications. 2007 Sep-Oct;21(5):294-9. — View Citation
Nicolau JC, Serrano CV Jr, Giraldez RR, Baracioli LM, Moreira HG, Lima F, Franken M, Kalil R, Ramires JA, Giugliano RP. In patients with acute myocardial infarction, the impact of hyperglycemia as a risk factor for mortality is not homogeneous across age-groups. Diabetes Care. 2012 Jan;35(1):150-2. doi: 10.2337/dc11-1170. Epub 2011 Oct 25. — View Citation
Park KW, Park JJ, Jeon KH, Kang SH, Oh IY, Yang HM, Cho HJ, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS. Clinical predictors of high posttreatment platelet reactivity to clopidogrel in Koreans. Cardiovasc Ther. 2012 Feb;30(1):5-11. doi: 10.1111/j.1755-5922.2010.00249.x. Epub 2010 Dec 6. — View Citation
Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. JAMA. 2010 Apr 14;303(14):1410-8. doi: 10.1001/jama.2010.405. — View Citation
Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012 Oct;35(10):2076-82. Epub 2012 Jun 11. Erratum in: Diabetes Care. 2014 Feb;37(2):587. — View Citation
Sanidas EA, Brener SJ, Maehara A, Généreux P, Witzenbichler B, El-Omar M, Fahy M, Mehran R, Gibson CM, Stone GW. Outcomes in diabetic patients undergoing primary percutaneous coronary intervention for acute anterior myocardial infarction: results from the INFUSE-AMI study. Catheter Cardiovasc Interv. 2014 Apr 1;83(5):704-10. doi: 10.1002/ccd.25203. Epub 2013 Oct 23. — View Citation
Scheen AJ. Cardiovascular effects of dipeptidyl peptidase-4 inhibitors: from risk factors to clinical outcomes. Postgrad Med. 2013 May;125(3):7-20. doi: 10.3810/pgm.2013.05.2659. Review. — View Citation
Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab. 2012 Apr;38(2):89-101. doi: 10.1016/j.diabet.2011.11.001. Epub 2011 Dec 22. Review. — View Citation
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-26. doi: 10.1056/NEJMoa1307684. Epub 2013 Sep 2. — View Citation
Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, Udell JA, Mosenzon O, Im K, Umez-Eronini AA, Pollack PS, Hirshberg B, Frederich R, Lewis BS, McGuire DK, Davidson J, Steg PG, Bhatt DL; SAVOR-TIMI 53 Steering Committee and Investigators*. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014 Oct 28;130(18):1579-88. doi: 10.1161/CIRCULATIONAHA.114.010389. Epub 2014 Sep 4. Erratum in: Circulation. 2015 Oct 13;132(15):e198. — View Citation
Selker HP, Beshansky JR, Sheehan PR, Massaro JM, Griffith JL, D'Agostino RB, Ruthazer R, Atkins JM, Sayah AJ, Levy MK, Richards ME, Aufderheide TP, Braude DA, Pirrallo RG, Doyle DD, Frascone RJ, Kosiak DJ, Leaming JM, Van Gelder CM, Walter GP, Wayne MA, Woolard RH, Opie LH, Rackley CE, Apstein CS, Udelson JE. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA. 2012 May 9;307(18):1925-33. doi: 10.1001/jama.2012.426. Epub 2012 Mar 27. — View Citation
Siegelaar SE, Kerr L, Jacober SJ, Devries JH. A decrease in glucose variability does not reduce cardiovascular event rates in type 2 diabetic patients after acute myocardial infarction: a reanalysis of the HEART2D study. Diabetes Care. 2011 Apr;34(4):855-7. doi: 10.2337/dc10-1684. — View Citation
Singla A, Antonino MJ, Bliden KP, Tantry US, Gurbel PA. The relation between platelet reactivity and glycemic control in diabetic patients with cardiovascular disease on maintenance aspirin and clopidogrel therapy. Am Heart J. 2009 Nov;158(5):784.e1-6. doi: 10.1016/j.ahj.2009.08.013. — View Citation
Standl E, Schnell O, Ceriello A. Postprandial hyperglycemia and glycemic variability: should we care? Diabetes Care. 2011 May;34 Suppl 2:S120-7. doi: 10.2337/dc11-s206. — View Citation
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasché P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S. Third universal definition of myocardial infarction. Circulation. 2012 Oct 16;126(16):2020-35. doi: 10.1161/CIR.0b013e31826e1058. Epub 2012 Aug 24. — View Citation
Umpierrez GE, Gianchandani R, Smiley D, Jacobs S, Wesorick DH, Newton C, Farrokhi F, Peng L, Reyes D, Lathkar-Pradhan S, Pasquel F. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013 Nov;36(11):3430-5. doi: 10.2337/dc13-0277. Epub 2013 Jul 22. — View Citation
Ussher JR, Drucker DJ. Cardiovascular biology of the incretin system. Endocr Rev. 2012 Apr;33(2):187-215. doi: 10.1210/er.2011-1052. Epub 2012 Feb 8. Review. — View Citation
Williams-Herman D, Round E, Swern AS, Musser B, Davies MJ, Stein PP, Kaufman KD, Amatruda JM. Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis. BMC Endocr Disord. 2008 Oct 27;8:14. doi: 10.1186/1472-6823-8-14. — View Citation
Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. — View Citation
* Note: There are 54 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | changes in glycemic control(glycemic variability assessed by standard deviation(SD) of capillary glucose samples). | Evaluated by measurements of capillary glucose samples by point-of care test during the length of coronary care unit(CCU) stay( expected average of 1 week).The glycemic variability will be obtained by calculating the standard deviation(SD). | baseline up to 1 week. | |
| Other | changes in glycemic control(glycemic variability assessed by continuous glucose monitoring system - CGM). | Evaluated by mean amplitude of glycemic excursions(MAGE) by the use of CGM | baseline and 48 (+-24) hours after drug exposure. | |
| Other | changes on platelet aggregability on pre-specified subgroups. | Changes on platelet aggregability will be compared on pre-specified subgroups: elderly (age >65 yrs-old) versus non-elderly; male versus female; smoking versus non-smoking patients; obese(BMI>30 Kg/m2) versus non-obese; length of diabetes; baseline glucose; glycated hemoglobin(HbA1c) < 9% and >9 % |
baseline and 4 (+-2)days after drug exposure. | |
| Other | rate of hypoglycemia during coronary care unit stay. | Rate of capillary glucose <70 mg/dL and <40 mg/dL,evaluated by capillary glucose measurements by point-of-care tests,during CCU stay(expected average of 1 week). | baseline up to 1 week . | |
| Other | total of insulin doses requirement during coronary care unit stay. | Comparison of the total requirement of correctional insulin between treatment and control arms after drug exposure. | baseline up to 1 week . | |
| Other | incidence of composite end-point. | Comparison the incidence of composite end-point between two arms.Composite end-point include: cardiovascular death; unstable angina; stroke ; hospitalization for heart failure; new non fatal myocardial infarction ; coronary revascularization . |
baseline and 30 (+-5) days after drug exposure | |
| Other | Infarct size. | Analysis of infarct size between two arms, by peak of creatine kinase(CK-MB) during CCU stay(expected average of 1 week). | baseline up to 1 week | |
| Other | cholesterylester transfer protein(CETP) mass | Analysis of CETP mass between two arms. | baseline | |
| Other | measure of safety, Number of participants with adverse effects by analysis on changes of serum level | Number of participants with adverse effects by analysis on changes of serum level of : alanine transferase; brain natriuretic peptide(BNP); amylase; lipase. |
baseline and 30(+-5) days after drug exposure. | |
| Primary | changes on platelet aggregability. | Comparison on platelet function between two therapeutic arms in a double-blind randomized fashion. Platelet aggregability will be measured 4(+-2) days after drug exposure,using a point-of-care test (VerifyNow Aspirin) in type 2 diabetic patients with AMI on dual antiplatelet therapy (ASA+ ticagrelor or clopidogrel according to institutional routine). | baseline and 4(+-2) days after drug exposure. | |
| Secondary | changes on platelet aggregability. | Primary outcome measure analyzed at baseline and 30(+-5) days after drug exposure. | baseline and 30(+-5) days after drug exposure. | |
| Secondary | platelet aggregability differences by two point-of-care methods. | Comparison on platelet aggregability by two different methods :Verify Now and Multiplate. | baseline and 4 (+-2) days after drug exposure. | |
| Secondary | platelet aggregability differences by two point-of-care methods. | Comparison on platelet aggregability by two different methods (Verify Now and Multiplate . | baseline and 30(+-5) days after drug exposure. |