Role of Immune Responses After Acute Myocardial Infarction (BATTLE-AMI)

Role of Innate and Adaptive Immunity After Acute Myocardial Infarction BATTLE-AMI Study (B And T Types of Lymphocytes Evaluation in Acute Myocardial Infarction)

The fascinating role of lymphocyte subtypes in the development of coronary artery disease may be a new strategic target for understanding and therapy of acute myocardial infarction. The determinants of cell viability are unknown, postulating that they arise from factors not only related to microcirculation or energy expenditure, but also to inflammatory and immune responses. Furthermore, the intense mobilization of progenitor cells secondary to myocardial infarction triggers large lymphocyte proliferation that colonizes plaques in development, contributing to recurrent ischemic outcomes. This project aims to evaluate the immune and metabolic mechanisms involved in the recovery of the ischemic myocardium and coronary disease progression.

Study Overview

• Status: Unknown
• Conditions: Myocardial Fibrosis
• Intervention / Treatment: Drug: Rosuvastatin plus ticagrelor; Drug: Simvastatin plus clopidogrel; Drug: Simvastatin plus ticagrelor; Drug: Rosuvastatin plus clopidogrel

Detailed Description

Specifically, the investigators will study the innate and adaptive immunity, with emphasis on lymphocytes subtypes involved in the early and late surrogate outcomes of patients with acute myocardial infarction, their characterization (B1, B2 and T lymphocytes) in cell culture and by flow-cytometry, and immune responses (IgM and IgG for oxLDL and specific epitopes of apoB). In addition, the project will evaluate new biomarkers identified by studies of metabolomics, as well as the corresponding signaling pathways. Therapeutic pharmacological strategies and changes on intestinal microbiota will be evaluated since the acute phase of myocardial infarction up to 6 months.

In the study, the investigators will compared four arms of combined therapy: clopidogrel with rosuvastatin; or clopidogrel with simvastatin; or ticagrelor with rosuvastatin; or ticagrelor with simvastatin. The investigator's hypothesis is that the improvement of microcirculation with rosuvastatin and ticagrelor (synergic pleiotropic effects) may decrease the infarcted mass area, resulting in better left ventricular ejection fraction when compared to the other combined therapies.

The monitoring and genotype of microbiota will be examined together the metabolomics and cardiac MRIs obtained at the acute phase of MI and after 1-mo and 6-mo FU.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francisco A Fonseca, MD, PhD; Phone Number: +55 11 992639082; Email: fahfonseca@terra.com.br
• Study Contact Backup: Name: Maria C Izar, MD, PhD; Phone Number: +55 11; Email: mcoizar@terra.com.br

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04040001
    • Recruiting
    • Hospital Sao Paulo - UNIFESP
    • Contact: Francisco A H Fonseca, MD, PhD; Phone Number: +5511992639082; Email: fahfonseca@terra.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Stable patients with ST elevation myocardial infarction (STEMI) treated with thrombolytics in the first 6h or the initial of symptoms of MI.

Exclusion Criteria:

1. Contraindication or known intolerance to the study drug protocol
2. Those with comorbidities such as neoplasm, renal insufficiency (stage 4 or higher)

Patients should be randomized in the first 24 hours of AMI and treated by one of the four combined therapies at least 2h prior to coronary angiogram followed by percutaneous intervention when necessary.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: rosuvastatin plus clopidogrel; rosuvastatin 40 mg and clopidogrel 75 mg	Drug: Rosuvastatin plus ticagrelor; Crestor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo; Other Names: Crestor & Brilinta; Drug: Simvastatin plus clopidogrel; Zocor 40 mg plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo; Other Names: Zocor plus Plavix; Drug: Simvastatin plus ticagrelor; Zocor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo; Other Names: Zocor & Brilinta
Active Comparator: Rosuvastatin plus ticagrelor; Rosuvastatin 40 mg plus ticagrelor 90 mg bid	Drug: Simvastatin plus clopidogrel; Zocor 40 mg plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo; Other Names: Zocor plus Plavix; Drug: Simvastatin plus ticagrelor; Zocor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo; Other Names: Zocor & Brilinta; Drug: Rosuvastatin plus clopidogrel; Crestor 40 mg daily plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo; Other Names: Crestor & Plavix
Active Comparator: simvastatin plus clopidogrel; Simvastatin 40 mg plus clopidogrel 75 mg	Drug: Rosuvastatin plus ticagrelor; Crestor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo; Other Names: Crestor & Brilinta; Drug: Simvastatin plus ticagrelor; Zocor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo; Other Names: Zocor & Brilinta; Drug: Rosuvastatin plus clopidogrel; Crestor 40 mg daily plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo; Other Names: Crestor & Plavix
Active Comparator: Simvastatin plus ticagrelor; Simvastatin 40 mg plus ticagrelor 90 mg bid	Drug: Rosuvastatin plus ticagrelor; Crestor 40 mg plus Brilinta 180 mg (initial dosis) and 90 mg bid up to 6-mo; Other Names: Crestor & Brilinta; Drug: Simvastatin plus clopidogrel; Zocor 40 mg plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo; Other Names: Zocor plus Plavix; Drug: Rosuvastatin plus clopidogrel; Crestor 40 mg daily plus Plavix 600 mg (initial dosis) and 75 mg daily up to 6-mo; Other Names: Crestor & Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the left ventricular function (MRI) between the four combined treatments, after STEMI	The effects of treatments on the left ventricular function will be measured by MRI	1-mo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the effects of the four combined therapies on the left ventricular function after STEMI	Variables will be examined by MRI	3-d
To compare the effects of the four combined therapies on the left ventricular function after STEMI	Variables will be examined by MRI	6-mo
To compare the effects of the four combined therapies on the infarcted mass area after STEMI	Variables will be examined by MRI	1-mo
To compare the effects of the four combined therapies on the infarcted mass area after STEMI	Variables will be examined by MRI	6-mo
To compare the effects of the four combined therapies on the percentage of subjects with left ventricular ejection fraction < 40% after STEMI	Variables will be examined by MRI	1-mo
To compare the effects of the four combined therapies on the percentage of subjects with left ventricular ejection fraction < 40% after STEMI	Variables will be examined by MRI	6-mo
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI	Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI	1-d
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI	Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI	1-mo
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction after STEMI	Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI	6-mo
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI	Lymphocyte subtypes quantified by flow-cytometry and infarcted mass area by MRI	1-d
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI	Lymphocyte subtypes quantified by flow-cytometry and infarcted mass area by MRI	1-mo
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with infarcted mass area after STEMI	Lymphocyte subtypes quantified by flow-cytometry and infarcted mass area by MRI	6-mo
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI	Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI	1-d
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI	Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI	1-mo
To quantify the percentage and absolute number of B1, B2, TCD4, and TCD8 subtypes of lymphocytes and their correlation with left ventricular ejection fraction <40% after STEMI	Lymphocyte subtypes quantified by flow-cytometry and left ventricular ejection fraction by MRI	6-mo

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between gut microbiota and diabetes status after STEMI	Intestinal microbiota will be genotyped and diabetes status (non-diabetic, pre-diabetic or diabetic) according to HbA1c levels.	1-3d
Relationship between gut microbiota and diabetes status after STEMI	Intestinal microbiota will be genotyped and diabetes status (non-diabetic, pre-diabetic or diabetic) according to HbA1c levels.	1-mo
Relationship between gut microbiota and diabetes status	Intestinal microbiota will be genotyped and diabetes status (non-diabetic, pre-diabetic or diabetic) according to HbA1c levels.	6-mo
Relationship between gut microbiota and metabolomics	Intestinal microbiota will be genotyped and metabolomics by LC/MS-MS	1-3d
Relationship between gut microbiota and metabolomics	Intestinal microbiota will be genotyped and metabolomics by LC/MS-MS	1-mo
Relationship between gut microbiota and metabolomics	Intestinal microbiota will be genotyped and metabolomics by LC/MS-MS	6-mo
Comparison between the four arm of combined therapies on microparticles and endothelial progenitor cells	Endothelial, platelet, and monocyte-derived microparticles as well as endothelial progenitor cells will be quantified by flow-cytometry	1-d
Comparison between the four arm of combined therapies on microparticles and endothelial progenitor cells	Endothelial, platelet, and monocyte-derived microparticles as well as endothelial progenitor cells will be quantified by flow-cytometry	1-mo
Comparison between the four arm of combined therapies on microparticles and endothelial progenitor cells	Endothelial, platelet, and monocyte-derived microparticles as well as endothelial progenitor cells will be quantified by flow-cytometry	6-mo
Correlation between the severity of coronary disease with antibodies against oxidized LDL and peptide D of apolipoprotein B of LDL	Antibodies IgG and IgM against oxidized LDL as well as against peptide D of LDL will be quantified by ELISA. Coronary disease severity will be quantified by the Gensini Score	1-d
Comparison between the four arms of combined therapies on TIMI flow grade and blush grade	TIMI flow grade and blush grade will be determined based on coronary angiogram obtained at baseline by two independent and blinded certified invasive cardiologists	1-d
Relationship between no-reflow images obtained at MRI with metabolomics	Metabolomics will be determined by LC/MS-MS and images by MRI	1-d
Relationship between no-reflow images obtained at MRI with metabolomics	Metabolomics will be determined by LC/MS-MS and images by MRI	1-mo
Relationship between no-reflow images obtained at MRI with metabolomics	Metabolomics will be determined by LC/MS-MS and images by MRI	6-mo

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Francisco A Fonseca, MD, PhD, Federal University of São Paulo

Publications and helpful links

General Publications

• McCrohon JA, Moon JC, Prasad SK, McKenna WJ, Lorenz CH, Coats AJ, Pennell DJ. Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation. 2003 Jul 8;108(1):54-9. doi: 10.1161/01.CIR.0000078641.19365.4C. Epub 2003 Jun 23.
• Libby P, Ridker PM, Hansson GK; Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009 Dec 1;54(23):2129-38. doi: 10.1016/j.jacc.2009.09.009.
• Quyyumi AA, Waller EK, Murrow J, Esteves F, Galt J, Oshinski J, Lerakis S, Sher S, Vaughan D, Perin E, Willerson J, Kereiakes D, Gersh BJ, Gregory D, Werner A, Moss T, Chan WS, Preti R, Pecora AL. CD34(+) cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent. Am Heart J. 2011 Jan;161(1):98-105. doi: 10.1016/j.ahj.2010.09.025.
• Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.
• Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009 Mar 10;53(10):849-56. doi: 10.1016/j.jacc.2008.11.030.
• Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. doi: 10.1056/NEJMoa0807646. Epub 2008 Nov 9.
• Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4.
• Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, Macfadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Trial Study Group. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009 Apr 4;373(9670):1175-82. doi: 10.1016/S0140-6736(09)60447-5. Epub 2009 Mar 28.
• Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8. Erratum In: N Engl J Med. 2006 Feb 16;354(7):778.
• Glynn RJ, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Ridker PM. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009 Apr 30;360(18):1851-61. doi: 10.1056/NEJMoa0900241. Epub 2009 Mar 29.
• Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.
• 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.
• Fonseca FA, Izar MC, Fuster V, Gallo R, Padurean A, Fallon JT, Schachter EN, Chesebro JH, Badimon JJ. Chronic endothelial dysfunction after oversized coronary balloon angioplasty in pigs: a 12-week follow-up of coronary vasoreactivity in vivo and in vitro. Atherosclerosis. 2001 Jan;154(1):61-9. doi: 10.1016/s0021-9150(00)00458-5.
• Silva EP, Fonseca FA, Ihara SS, Izar MC, Lopes IL, Pinto LE, Badimon JJ, Tuffik S, Paiva TB, Kasinski N, de Paola AV, Carvalho AC. Early benefits of pravastatin to experimentally induced atherosclerosis. J Cardiovasc Pharmacol. 2002 Mar;39(3):389-95. doi: 10.1097/00005344-200203000-00010.
• Fonseca FA, Paiva TB, Silva EG, Ihara SS, Kasinski N, Martinez TL, Filho EE. Dietary magnesium improves endothelial dependent relaxation of balloon injured arteries in rats. Atherosclerosis. 1998 Aug;139(2):237-42. doi: 10.1016/s0021-9150(98)00069-0.
• Fonseca FA, Ihara SS, Izar MC, Silva EP, Kasinski N, Lopes IE, Pinto LE, Paiva TB, Tufik S, de Paola AA, Carvalho AC. Hydrochlorothiazide abolishes the anti-atherosclerotic effect of quinapril. Clin Exp Pharmacol Physiol. 2003 Oct;30(10):779-85. doi: 10.1046/j.1440-1681.2003.03911.x.
• Ferreira WP, Bertolami MC, Santos SN, Barros MR, de Matos Barretto RB, Pontes SC Jr, Fonseca FH, Carvalho AC. One-month therapy with simvastatin restores endothelial function in hypercholesterolemic children and adolescents. Pediatr Cardiol. 2007 Jan-Feb;28(1):8-13. doi: 10.1007/s00246-005-1304-x. Epub 2007 Jan 25.
• Monteiro CM, Pinheiro LF, Izar MC, Barros SW, Vasco MB, Fischer SM, Povoa RM, Brandao SA, Santos AO, Oliveira L, Carvalho AC, Fonseca FA. Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event. Braz J Med Biol Res. 2010 Mar;43(3):297-302. doi: 10.1590/s0100-879x2010005000008. Epub 2010 Mar 5.
• da Silva EF, Fonseca FA, Franca CN, Ferreira PR, Izar MC, Salomao R, Camargo LM, Tenore SB, Lewi DS. Imbalance between endothelial progenitors cells and microparticles in HIV-infected patients naive for antiretroviral therapy. AIDS. 2011 Aug 24;25(13):1595-601. doi: 10.1097/QAD.0b013e32834980f4.
• Franca CN, Pinheiro LF, Izar MC, Brunialti MK, Salomao R, Bianco HT, Kasmas SH, Barbosa SP, de Nucci G, Fonseca FA. Endothelial progenitor cell mobilization and platelet microparticle release are influenced by clopidogrel plasma levels in stable coronary artery disease. Circ J. 2012;76(3):729-36. doi: 10.1253/circj.cj-11-1145. Epub 2011 Dec 28.
• Pomaro DR, Ihara SS, Pinto LE, Ueda I, Casarini DE, Ebihara F, Santos AO, Izar MC, Fonseca FA. High glucose levels abolish antiatherosclerotic benefits of ACE inhibition in alloxan-induced diabetes in rabbits. J Cardiovasc Pharmacol. 2005 Apr;45(4):295-300. doi: 10.1097/01.fjc.0000155384.64350.45.
• Relvas WG, Izar MC, Segreto HR, Giordani AJ, Ihara SS, Mariano M, Lopes JD, Popi AF, Helfenstein T, Pomaro D, Povoa RM, Carvalho AC, Fonseca FA. Resident peritoneal inflammatory cells are pivotal in the development of experimental atherosclerosis. J Atheroscler Thromb. 2010 Apr 30;17(4):378-85. doi: 10.5551/jat.3418. Epub 2010 Mar 9.
• Helfenstein T, Fonseca FA, Ihara SS, Bottos JM, Moreira FT, Pott H Jr, Farah ME, Martins MC, Izar MC. Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits. Int J Exp Pathol. 2011 Feb;92(1):40-9. doi: 10.1111/j.1365-2613.2010.00753.x.
• Feio CA, Izar MC, Ihara SS, Kasmas SH, Martins CM, Feio MN, Maues LA, Borges NC, Moreno RA, Povoa RM, Fonseca FA. Euterpe oleracea (acai) modifies sterol metabolism and attenuates experimentally-induced atherosclerosis. J Atheroscler Thromb. 2012;19(3):237-45. doi: 10.5551/jat.11205. Epub 2011 Dec 3.
• Albert MA, Glynn RJ, Fonseca FA, Lorenzatti AJ, Ferdinand KC, MacFadyen JG, Ridker PM. Race, ethnicity, and the efficacy of rosuvastatin in primary prevention: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Am Heart J. 2011 Jul;162(1):106-14.e2. doi: 10.1016/j.ahj.2011.03.032. Epub 2011 Jun 12.
• de Lima Sanches P, de Mello MT, Elias N, Fonseca FA, de Piano A, Carnier J, Oyama LM, Tock L, Tufik S, Damaso AR. Improvement in HOMA-IR is an independent predictor of reduced carotid intima-media thickness in obese adolescents participating in an interdisciplinary weight-loss program. Hypertens Res. 2011 Feb;34(2):232-8. doi: 10.1038/hr.2010.225. Epub 2010 Dec 2.
• Fonseca FA, Franca CN, Povoa RM, Izar MC. [Statins and stroke: potential mechanisms for neurovascular protection]. Rev Neurol. 2010 Nov 1;51(9):551-60. Spanish.
• Ridker PM, MacFadyen JG, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Study Group. Number needed to treat with rosuvastatin to prevent first cardiovascular events and death among men and women with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER). Circ Cardiovasc Qual Outcomes. 2009 Nov;2(6):616-23. doi: 10.1161/CIRCOUTCOMES.109.848473. Epub 2009 Sep 22.
• Brandao SA, Izar MC, Fischer SM, Santos AO, Monteiro CM, Povoa RM, Helfenstein T, Carvalho AC, Monteiro AM, Ramos E, Gidlund M, Figueiredo Neto AM, Fonseca FA. Early increase in autoantibodies against human oxidized low-density lipoprotein in hypertensive patients after blood pressure control. Am J Hypertens. 2010 Feb;23(2):208-14. doi: 10.1038/ajh.2009.214. Epub 2009 Nov 12.
• Fonseca FA, Izar MC. Primary prevention of vascular events in patients with high levels of C-reactive protein: the JUPITER study. Expert Rev Cardiovasc Ther. 2009 Sep;7(9):1041-56. doi: 10.1586/erc.09.93.
• Santos AO, Fonseca FA, Fischer SM, Monteiro CM, Brandao SA, Povoa RM, Bombig MT, Carvalho AC, Monteiro AM, Ramos E, Gidlund M, Figueiredo Neto AM, Izar MC. High circulating autoantibodies against human oxidized low-density lipoprotein are related to stable and lower titers to unstable clinical situation. Clin Chim Acta. 2009 Aug;406(1-2):113-8. doi: 10.1016/j.cca.2009.06.005. Epub 2009 Jun 10.
• Ridker PM, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Khurmi NS, Koenig W, Libby P, Lorenzatti AJ, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Trial Study Group. Baseline characteristics of participants in the JUPITER trial, a randomized placebo-controlled primary prevention trial of statin therapy among individuals with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein. Am J Cardiol. 2007 Dec 1;100(11):1659-64. doi: 10.1016/j.amjcard.2007.09.072. Epub 2007 Oct 24.
• Ramos SC, Fonseca FA, Kasmas SH, Moreira FT, Helfenstein T, Borges NC, Moreno RA, Rezende VM, Silva FC, Izar MC. The role of soluble fiber intake in patients under highly effective lipid-lowering therapy. Nutr J. 2011 Aug 2;10:80. doi: 10.1186/1475-2891-10-80.
• Izar MC, Tegani DM, Kasmas SH, Fonseca FA. Phytosterols and phytosterolemia: gene-diet interactions. Genes Nutr. 2011 Feb;6(1):17-26. doi: 10.1007/s12263-010-0182-x. Epub 2010 Aug 28.
• Fonseca HA, Izar MC, Bianco HT, Fonseca FA. Ezetimibe, oxidized low density lipoprotein, Lp (a), and dyslipidemia. J Atheroscler Thromb. 2010 Aug 31;17(8):888. doi: 10.5551/jat.5918. Epub 2010 Aug 10. No abstract available.
• Kasmas SH, Izar MC, Franca CN, Ramos SC, Moreira FT, Helfenstein T, Moreno RA, Borges NC, Figueiredo-Neto AM, Fonseca FA. Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies. Braz J Med Biol Res. 2012 Nov;45(11):1095-101. doi: 10.1590/s0100-879x2012007500118. Epub 2012 Jul 19.
• da Fonseca HA, Fonseca FA, Monteiro AM, Farias NC Jr, Bianco HT, Brandao SA, Povoa RM, Gidlund M, Izar MC. Inflammatory environment and immune responses to oxidized LDL are linked to systolic and diastolic blood pressure levels in hypertensive subjects. Int J Cardiol. 2012 May 17;157(1):131-3. doi: 10.1016/j.ijcard.2012.03.041. Epub 2012 Mar 28. No abstract available.
• Izar MC, Fonseca HA, Pinheiro LF, Monteiro CM, Povoa RM, Monteiro AM, Figueiredo-Neto AM, Gidlund MA, Fonseca FA. Adaptive immunity is related to coronary artery disease severity after acute coronary syndrome in subjects with metabolic syndrome. Diab Vasc Dis Res. 2013 Jan;10(1):32-9. doi: 10.1177/1479164112443374. Epub 2012 Apr 23.
• Colossimo AP, Costa Fde A, Riera AR, Bombig MT, Lima VC, Fonseca FA, Izar MC, L Filho B, Souza D, Povoa RM. Electrocardiogram sensitivity in left ventricular hypertrophy according to gender and cardiac mass. Arq Bras Cardiol. 2011 Sep;97(3):225-31. doi: 10.1590/s0066-782x2011005000085. Epub 2011 Aug 12. English, Portuguese.
• Costa Fde A, Bombig MT, de Lima VC, de Souza D, Luna Filho B, Fonseca FH, Izar MC, da Costa W, Riera AR, Povoa R. Geometric patterns of left ventricular hypertrophy and electrocardiography. Int J Cardiol. 2011 Sep 15;151(3):374-5. doi: 10.1016/j.ijcard.2011.06.103. Epub 2011 Jul 18. No abstract available.
• Marui FR, Bombig MT, Francisco YA, Thalenberg JM, Fonseca FA, Souza Dd, Costa Fde A, Izar MC, Carvalho AC, Povoa R. [Assessment of resistant hypertension with home blood pressure monitoring]. Arq Bras Cardiol. 2010 Oct;95(4):536-40. doi: 10.1590/s0066-782x2010005000120. Epub 2010 Sep 8. Multiple languages.
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Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: March 10, 2015
• First Submitted That Met QC Criteria: April 27, 2015
• First Posted (Estimate): April 28, 2015

Study Record Updates

• Last Update Posted (Estimate): June 11, 2015
• Last Update Submitted That Met QC Criteria: June 10, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: MRI; Ventricular function, left
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ticagrelor; Clopidogrel; Rosuvastatin Calcium; Simvastatin
• Other Study ID Numbers: EPM/UNIFESP; FAPESP (Other Grant/Funding Number: 2010/50120-4)