EValuation of REsidual Platelet REactivity After Acute Coronary Syndrome (ST+/ST-) in HIV

NCT ID: NCT02380391

Last Updated: 2015-03-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 260 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2014-06-30

Brief Summary

Elevated on-treatment platelet reactivity is an independent risk factor of major adverse cardiovascular events following percutaneous coronary intervention or ACS. People living with HIV patients have a higher risk of recurrent events after ACS than people without HIV.

The investigators hypothesized that this increased risk is driven by higher platelet reactivity.

Using a nested case-control study design, HIV-infected and HIV-uninfected patients with a first episode of Acute Coronary Syndrome (ACS) treated with percutaneous coronary intervention were matched for age, sex, known diabetes mellitus and anti-platelet therapy.

The primary end-point was the residual platelet reactivity (RPA) on dual antiplatelet therapy assessed by light transmission aggregometry (LTA, 20µM ADP).

The study was conducted in a two large public university hospitals in central Paris, France.

Detailed Description

Study design :

Research of routine care - hospital based, two site, nested case-control study, conducted in the Institute of Cardiology within the Pitie-Salpetriere University Hospital and the Cardiac Center of the Saint Antoine University Hospital.

Number of participants :

Group 1 : n=80 HIV seropositive participants (HIV+) Group 2 : n=160 HIV seronegative participants (HIV-) Sample size calculation based on : 10% absolute difference between the two groups for maximum platelet aggregation (MPA) to residual platelet aggregation (RPA) ratio calculated MPA/RPA for each antiplatelet drug (Aspirin, Clopidogrel, Prasugrel).

Study justification :

Platelet function is a risk marker independent of ACS recurrence risk. People living with HIV who have a premature coronary artery disease, revealed by an ACS event, more frequently experience ischemic recurrence than people without HIV.

Hypothesis :

Due to their elevated residual platelet reactivity, people living with HIV present more frequent ACS recurrence following a first event than people without HIV.

Primary objective :

Determine if there is an influence of HIV and antiretroviral medications on the platelet reactivity of individuals under oral antiplatelet treatment. PLatelet reactivity will be assessed between one week to 3 years after the initial acute coronary syndrome under dual antiplatelet therapy.

Methods :

Platelet aggregation measured by :

1. Light transmission aggregometry (LTA, 20µM adenosine diphosphate receptor inhibitor (ADP) and 5µM of arachidonic acid (AA))

2. Point of care VerifyNowRM P2Y12 and ARU (P2Y12 Reaction Units and ARU Aspirin Reaction Units)

3. Flow cytometry (VAsodilatator Simulated Phosphoprotein (VASP))

Conditions

Acute Coronary Syndrome; HIV

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

People living with HIV (HIV+)

Adults experiencing first episode of ACS treated with percutaneous coronary intervention.

No interventions assigned to this group

People without HIV (HIV-)

Adults experiencing first episode of ACS treated with percutaneous coronary intervention, matched to HIV+ on age, sex, known diabetes mellitus, and anti-platelet therapy.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

HIV+ group

• HIV-1 seropositive, known for a minimum of 6 months
• 18 years of age or older
• Hospitalisation for acute coronary syndrome a minimum of one month prior to inclusion (with or without coronary revascularisation)
• Under any antiplatelet therapy
• Willing and able to give informed consent to participate in the study

HIV- group

• HIV seronegative
• 18 years of age or older
• Hospitalisation for acute coronary syndrome a minimum of one month prior to inclusion (with or without coronary revascularisation)
• Under any antiplatelet therapy
• Willing and able to give informed consent to participate in the study

Exclusion Criteria

• Refusal to give or sign informed consent
• Presence of a counterindication or non-indication for antiplatelet therapy
• Not associated with a social security regime (no health insurance)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Groupe Hospitalier Pitie-Salpetriere

OTHER

Sponsor Role: collaborator

Saint Antoine University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Franck Boccara

Professor of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Franck Boccara, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Saint Antoine University Hospital

Ariel Cohen, MD, PhD

Role: STUDY_DIRECTOR

Saint Antoine University Hospital

Jean Philippe Collet, MD, PhD

Role: STUDY_DIRECTOR

ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP) and Université Paris 6, INSERM, Paris, France

Johanne Silvain, MD, PhD

Role: STUDY_DIRECTOR

ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP) and Université Paris 6, INSERM, Paris, France

Gilles Montalescot, MD, PhD

Role: STUDY_CHAIR

ACTION Study Group, Unité de Recherche Clinique-Hôpital Lariboisière (APHP) and Université Paris 6, INSERM, Paris, France

Locations

Cardiology department

Paris, , France

Countries

France

References

Parodi G, Marcucci R, Valenti R, Gori AM, Migliorini A, Giusti B, Buonamici P, Gensini GF, Abbate R, Antoniucci D. High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA. 2011 Sep 21;306(11):1215-23. doi: 10.1001/jama.2011.1332.

Reference Type: BACKGROUND

PMID: 21934054 (View on PubMed)

Boccara F, Mary-Krause M, Teiger E, Lang S, Lim P, Wahbi K, Beygui F, Milleron O, Gabriel Steg P, Funck-Brentano C, Slama M, Girard PM, Costagliola D, Cohen A; Prognosis of Acute Coronary Syndrome in HIV-infected patients (PACS) Investigators. Acute coronary syndrome in human immunodeficiency virus-infected patients: characteristics and 1 year prognosis. Eur Heart J. 2011 Jan;32(1):41-50. doi: 10.1093/eurheartj/ehq372. Epub 2010 Oct 21.

Reference Type: BACKGROUND

PMID: 20965887 (View on PubMed)

Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, Boccara F, Bingham A, Costagliola D; French Hospital Database on HIV-ANRS CO4. Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS. 2010 May 15;24(8):1228-30. doi: 10.1097/QAD.0b013e328339192f.

Reference Type: BACKGROUND

PMID: 20400883 (View on PubMed)

Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12. doi: 10.1210/jc.2006-2190. Epub 2007 Apr 24.

Reference Type: BACKGROUND

PMID: 17456578 (View on PubMed)

Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, d'Arminio Monforte A, Pradier C, Morfeldt L, Mateu S, Law M, El-Sadr W, De Wit S, Sabin CA, Phillips AN, Lundgren JD; DAD study group. Cardiovascular disease risk factors in HIV patients--association with antiretroviral therapy. Results from the DAD study. AIDS. 2003 May 23;17(8):1179-93. doi: 10.1097/01.aids.0000060358.78202.c1.

Reference Type: BACKGROUND

PMID: 12819520 (View on PubMed)

Kaplan RC, Kingsley LA, Sharrett AR, Li X, Lazar J, Tien PC, Mack WJ, Cohen MH, Jacobson L, Gange SJ. Ten-year predicted coronary heart disease risk in HIV-infected men and women. Clin Infect Dis. 2007 Oct 15;45(8):1074-81. doi: 10.1086/521935. Epub 2007 Sep 12.

Reference Type: BACKGROUND

PMID: 17879928 (View on PubMed)

Patel P, Hanson DL, Sullivan PS, Novak RM, Moorman AC, Tong TC, Holmberg SD, Brooks JT; Adult and Adolescent Spectrum of Disease Project and HIV Outpatient Study Investigators. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med. 2008 May 20;148(10):728-36. doi: 10.7326/0003-4819-148-10-200805200-00005.

Reference Type: BACKGROUND

PMID: 18490686 (View on PubMed)

Saves M, Chene G, Ducimetiere P, Leport C, Le Moal G, Amouyel P, Arveiler D, Ruidavets JB, Reynes J, Bingham A, Raffi F; French WHO MONICA Project and the APROCO (ANRS EP11) Study Group. Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population. Clin Infect Dis. 2003 Jul 15;37(2):292-8. doi: 10.1086/375844. Epub 2003 Jul 7.

Reference Type: BACKGROUND

PMID: 12856222 (View on PubMed)

Grinspoon SK. Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus. Am J Med. 2005 Apr;118 Suppl 2:23S-28S. doi: 10.1016/j.amjmed.2005.01.047.

Reference Type: BACKGROUND

PMID: 15903292 (View on PubMed)

Capeau J. From lipodystrophy and insulin resistance to metabolic syndrome: HIV infection, treatment and aging. Curr Opin HIV AIDS. 2007 Jul;2(4):247-52. doi: 10.1097/COH.0b013e3281e66919.

Reference Type: BACKGROUND

PMID: 19372895 (View on PubMed)

Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr. 2009 Jul 1;51(3):268-73. doi: 10.1097/QAI.0b013e3181a9992c.

Reference Type: BACKGROUND

PMID: 19387353 (View on PubMed)

Mangili A, Polak JF, Quach LA, Gerrior J, Wanke CA. Markers of atherosclerosis and inflammation and mortality in patients with HIV infection. Atherosclerosis. 2011 Feb;214(2):468-73. doi: 10.1016/j.atherosclerosis.2010.11.013. Epub 2010 Nov 17.

Reference Type: BACKGROUND

PMID: 21130995 (View on PubMed)

Coll B, Parra S, Alonso-Villaverde C, Aragones G, Montero M, Camps J, Joven J, Masana L. The role of immunity and inflammation in the progression of atherosclerosis in patients with HIV infection. Stroke. 2007 Sep;38(9):2477-84. doi: 10.1161/STROKEAHA.106.479030. Epub 2007 Aug 2.

Reference Type: BACKGROUND

PMID: 17673719 (View on PubMed)

Kaplan RC, Kingsley LA, Gange SJ, Benning L, Jacobson LP, Lazar J, Anastos K, Tien PC, Sharrett AR, Hodis HN. Low CD4+ T-cell count as a major atherosclerosis risk factor in HIV-infected women and men. AIDS. 2008 Aug 20;22(13):1615-24. doi: 10.1097/QAD.0b013e328300581d.

Reference Type: BACKGROUND

PMID: 18670221 (View on PubMed)

Torre D, Pugliese A. Platelets and HIV-1 infection: old and new aspects. Curr HIV Res. 2008 Sep;6(5):411-8. doi: 10.2174/157016208785861140.

Reference Type: BACKGROUND

PMID: 18855651 (View on PubMed)

Satchell CS, Cotter AG, O'Connor EF, Peace AJ, Tedesco AF, Clare A, Lambert JS, Sheehan GJ, Kenny D, Mallon PW. Platelet function and HIV: a case-control study. AIDS. 2010 Mar 13;24(5):649-57. doi: 10.1097/QAD.0b013e328336098c.

Reference Type: BACKGROUND

PMID: 20177361 (View on PubMed)

Boccara F, Mary-Krause M, Teiger E, et al. HIV-infected patients have an increased risk of recurrent ischemic events as compared to the general population after an acute coronary syndrome. Paper presented at: American Heart Association; November 15th, 2011, 2011; Orlando, USA.

Reference Type: BACKGROUND

Baker JV, Neuhaus J, Duprez D, Kuller LH, Tracy R, Belloso WH, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Nixon DE, Paton NI, Neaton JD; INSIGHT SMART Study Group. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. J Acquir Immune Defic Syndr. 2011 Jan 1;56(1):36-43. doi: 10.1097/QAI.0b013e3181f7f61a.

Reference Type: BACKGROUND

PMID: 20930640 (View on PubMed)

Scaradavou A. HIV-related thrombocytopenia. Blood Rev. 2002 Mar;16(1):73-6. doi: 10.1054/blre.2001.0188.

Reference Type: BACKGROUND

PMID: 11914001 (View on PubMed)

von Hentig N, Forster AK, Kuczka K, Klinkhardt U, Klauke S, Gute P, Staszewski S, Harder S, Graff J. Platelet-leucocyte adhesion markers before and after the initiation of antiretroviral therapy with HIV protease inhibitors. J Antimicrob Chemother. 2008 Nov;62(5):1118-21. doi: 10.1093/jac/dkn333. Epub 2008 Aug 27.

Reference Type: BACKGROUND

PMID: 18753189 (View on PubMed)

Corrales-Medina VF, Simkins J, Chirinos JA, Serpa JA, Horstman LL, Jy W, Ahn YS. Increased levels of platelet microparticles in HIV-infected patients with good response to highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2010 Jun;54(2):217-8. doi: 10.1097/QAI.0b013e3181c8f4c9. No abstract available.

Reference Type: BACKGROUND

PMID: 20505474 (View on PubMed)

Baker J, Ayenew W, Quick H, Hullsiek KH, Tracy R, Henry K, Duprez D, Neaton JD. High-density lipoprotein particles and markers of inflammation and thrombotic activity in patients with untreated HIV infection. J Infect Dis. 2010 Jan 15;201(2):285-92. doi: 10.1086/649560.

Reference Type: BACKGROUND

PMID: 19954384 (View on PubMed)

Daali Y, Ancrenaz V, Bosilkovska M, Dayer P, Desmeules J. Ritonavir inhibits the two main prasugrel bioactivation pathways in vitro: a potential drug-drug interaction in HIV patients. Metabolism. 2011 Nov;60(11):1584-9. doi: 10.1016/j.metabol.2011.03.015. Epub 2011 May 6.

Reference Type: BACKGROUND

PMID: 21550074 (View on PubMed)

Collet JP, Cayla G, Cuisset T, Elhadad S, Range G, Vicaut E, Montalescot G. Randomized comparison of platelet function monitoring to adjust antiplatelet therapy versus standard of care: rationale and design of the assessment with a double randomization of (1) a fixed dose versus a monitoring-guided dose of aspirin and clopidogrel after DES implantation, and (2) treatment interruption versus continuation, 1 year after stenting (ARCTIC) study. Am Heart J. 2011 Jan;161(1):5-12.e5. doi: 10.1016/j.ahj.2010.09.029.

Reference Type: BACKGROUND

PMID: 21167334 (View on PubMed)

Silvain J, Bellemain-Appaix A, Barthelemy O, Beygui F, Collet JP, Montalescot G. Optimal use of thienopyridines in non-ST-elevation acute coronary syndrome following CURRENT-OASIS 7. Circ Cardiovasc Interv. 2011 Feb 1;4(1):95-103. doi: 10.1161/CIRCINTERVENTIONS.109.910406. No abstract available.

Reference Type: BACKGROUND

PMID: 21325198 (View on PubMed)

Silvain J, Collet JP, Nagaswami C, Beygui F, Edmondson KE, Bellemain-Appaix A, Cayla G, Pena A, Brugier D, Barthelemy O, Montalescot G, Weisel JW. Composition of coronary thrombus in acute myocardial infarction. J Am Coll Cardiol. 2011 Mar 22;57(12):1359-67. doi: 10.1016/j.jacc.2010.09.077.

Reference Type: BACKGROUND

PMID: 21414532 (View on PubMed)

Hulot JS, Collet JP, Cayla G, Silvain J, Allanic F, Bellemain-Appaix A, Scott SA, Montalescot G. CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv. 2011 Oct 1;4(5):422-8. doi: 10.1161/CIRCINTERVENTIONS.111.963025. Epub 2011 Oct 4.

Reference Type: BACKGROUND

PMID: 21972404 (View on PubMed)

Silvain J, Cayla G, Hulot JS, Finzi J, Kerneis M, O'Connor SA, Bellemain-Appaix A, Barthelemy O, Beygui F, Collet JP, Montalescot G. High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study. Eur Heart J. 2012 May;33(10):1241-9. doi: 10.1093/eurheartj/ehr407. Epub 2011 Nov 7.

Reference Type: BACKGROUND

PMID: 22067090 (View on PubMed)

Other Identifiers

EVERE2ST-HIV

Identifier Type: -

Identifier Source: org_study_id