Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639]

Hrvoje Gasparovic, Mate Petricevic, Tomislav Kopjar, Zeljko Djuric, Lucija Svetina, Bojan Biocina, Hrvoje Gasparovic, Mate Petricevic, Tomislav Kopjar, Zeljko Djuric, Lucija Svetina, Bojan Biocina

Abstract

Background: Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events.

Methods: Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology) as well as bleeding events will be recorded.

Discussion: This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639).

Figures

Figure 1
Figure 1
Flowchart detailing the screening algorithm for patient recruitment, followed by subsequent randomization into the aspirin monotherapy or dual antiplatelet therapy groups. CABG, coronary artery bypass grafting; MEA, multiple electrode aggregometry; ASPI, cyclooxygenase dependent platelet aggregation, AUC, area under the curve; ASA, acetylsalicylic acid; MACCE, major adverse cardiac and cerebrovascular events.

References

    1. Libby P. In: The vascular biology of atherosclerosis. 9. Bonow RO, Mann DLm Zipes DP, Libby P, editor. Philadelphia, PA: Elsevier Saunders; 2002. Braunwald’s heart disease: A textbook of cardiovascular medicine; pp. 897–913.
    1. Taggart DP, Altman DG, Gray AM, Lees B, Nugara F, Yu LM, Campbell H, Flather M. ART Investigators. Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART) Eur Heart J. 2010;31:2470–2481. doi: 10.1093/eurheartj/ehq318.
    1. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86. doi: 10.1136/bmj.324.7329.71.
    1. Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, Nashef SA. EACTS Audit and Guidelines Committee. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg. 2008;34:73–92. doi: 10.1016/j.ejcts.2008.02.024.
    1. Bollati M, Gaita F, Anselmino M. Antiplatelet combinations for prevention of atherothrombotic events. Vasc Health Risk Manag. 2011;7:23–30.
    1. Mengistu AM, Mayer J, Boldt J, Röhm KD, Suttner SW. Usefulness of monitoring platelet function by multiple electrode aggregometry in primary coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2011;25:42. doi: 10.1053/j.jvca.2010.02.008.
    1. Ben-Dor I, Kleiman NS, Lev E. Assessment, mechanisms, and clinical implication of variability in platelet response to aspirin and clopidogrel therapy. Am J Cardiol. 2009;104:227–233. doi: 10.1016/j.amjcard.2009.03.022.
    1. Fintel DJ. Antiplatelet therapy in cerebrovascular disease: implications of Management of Artherothrombosis with Clopidogrel in High-risk Patients and the Clopidogrel for High Artherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance studies’ results for cardiologists. Clin Cardiol. 2007;30:604–614. doi: 10.1002/clc.20154.
    1. Kasotakis G, Pipinos II, Lynch TG. Current evidence and clinical implications of aspirin resistance. J Vasc Surg. 2009;50:1500–1510. doi: 10.1016/j.jvs.2009.06.023.
    1. Schulz KF, Altman DG, Moher D. CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials. 2010;11:32. doi: 10.1186/1745-6215-11-32.
    1. Petricevic MBB, Konosic S, Kopjar T, Milosevic M, Gasparovic H. In: 21st World Congress World Society of Cardio-Thoracic Surgeons. Forum THS, editor. Berlin, Germany: Abstract book; 2011. Definition of acetylsalicylic acid resistance using multiple electrode aggregometry in patients following coronary artery bypass grafting; pp. 70–71.
    1. Skoric B, Milicic D, Lovric D, Gornik I, Skoric KN, Sertic J. Initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction is related to platelet response to aspirin. Int J Cardiol. 2010;140:356–358. doi: 10.1016/j.ijcard.2008.11.031.
    1. Jambor C, Weber CF, Gerhardt K, Dietrich W, Spannagl M, Heindl B, Zwissler B. Whole blood multiple electrode aggregometry is a reliable point-of-care test of aspirin-induced platelet dysfunction. Anesth Analg. 2009;109:25–31. doi: 10.1213/ane.0b013e3181a27d10.
    1. von Pape KW, Dzijan-Horn M, Bohner J, Spannagl M, Weisser H, Calatzis A. Control of aspirin effect in chronic cardiovascular patients using two whole blood platelet function assays. PFA-100 and Multiplate. Hämostaseologie. 2007;27:155–160.
    1. Research randomizer. .
    1. Kalb ML, Potura L, Scharbert G, Kozek-Langenecker SA. The effect of ex vivo anticoagulants on whole blood platelet aggregation. Platelets. 2009;20:7–11. doi: 10.1080/09537100802364076.
    1. Truss NJ, Armstrong PC, Liverani E, Vojnovic I, Warner TD. Heparin but not citrate anticoagulation of blood preserves platelet function for prolonged periods. J Thromb Haemost. J Thromb Haemost 2009;7:1897–1905.
    1. Toth O, Calatzis A, Penz S, Losonczy H, Siess W. Multiple electrode aggregometry: a new device to measure platelet aggregation in whole blood. Thromb Haemost. 2006;96:781–788.
    1. Calatzis A, Krueger WB. A new approach to platelet function analysis in whole blood- the multiplate analyzer. Platelets. 2004;15:479–517.
    1. Thygesen K, Alpert JS, White HD. on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Circulation. 2007;116:2634–2653. doi: 10.1161/CIRCULATIONAHA.107.187397.
    1. Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T. American Heart Association; American Stroke Association Council on Stroke; Council on Cardiovascular Radiology and Intervention; American Academy of Neurology. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline. Stroke. 2006;37:577–617. doi: 10.1161/01.STR.0000199147.30016.74.
    1. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123:2736–2747. doi: 10.1161/CIRCULATIONAHA.110.009449.
    1. Kulik A, Le May MR, Voisine P, Tardif JC, Delarochelliere R, Naidoo S, Wells GA, Mesana TG, Ruel M. Aspirin plus clopidogrel versus aspirin alone after coronary artery bypass grafting: the clopidogrel after surgery for coronary artery disease (CASCADE) Trial. Circulation. 2010;122:2680–2687. doi: 10.1161/CIRCULATIONAHA.110.978007.
    1. Gao G, Zheng Z, Pi Y, Lu B, Lu J, Hu S. Aspirin plus clopidogrel therapy increases early venous graft patency after coronary artery bypass surgery a single-center, randomized, controlled trial. J Am Coll Cardiol. 2010;9(56):1639–1643.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit