[en] BACKGROUND: Glycoprotein IIb/IIIa inhibitors are indicated in patients with acute coronary syndromes who are undergoing an invasive procedure. The optimal timing of the initiation of such therapy is unknown. METHODS: We compared a strategy of early, routine administration of eptifibatide with delayed, provisional administration in 9492 patients who had acute coronary syndromes without ST-segment elevation and who were assigned to an invasive strategy. Patients were randomly assigned to receive either early eptifibatide (two boluses, each containing 180 microg per kilogram of body weight, administered 10 minutes apart, and a standard infusion > or = 12 hours before angiography) or a matching placebo infusion with provisional use of eptifibatide after angiography (delayed eptifibatide). The primary efficacy end point was a composite of death, myocardial infarction, recurrent ischemia requiring urgent revascularization, or the occurrence of a thrombotic complication during percutaneous coronary intervention that required bolus therapy opposite to the initial study-group
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol 2007;50(7):e1-e157. [Erratum, J Am Coll Cardiol 2008;51:974.]
Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J 2007;28:1598-1660
ESPRIT Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000;356:2037-2044 [Erratum, Lancet 2001;357:1370.]
Bolognese L, Falsini G, Liistro F, et al. Randomized comparison of upstream tirofiban versus downstream high bolus dose tirofiban or abciximab on tissue-level perfusion and troponin release in high-risk acute coronary syndromes treated with percutaneous coronary interventions: the EVEREST trial. J Am Coll Cardiol 2006;47:522-528 (Pubitemid 43170839)
Giugliano RP, Newby LK, Harrington RA, et al. The Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial: a randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndrome - study design and rationale. Am Heart J 2005;149:994-1002. (Pubitemid 40848143)
Cohen M, Mahaffey KW, Pieper K, et al. A subgroup analysis of the impact of prerandomization antithrombin therapy on outcomes in the SYNERGY trial: enoxaparin versus unfractionated heparin in non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol 2006;48:1346-1354 (Pubitemid 44436804)
The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998;338:1498-1505
The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1998;338:1488-1497 [Erratum, N Engl J Med 1998;339:415.]
The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998;339:436-443 (Pubitemid 28377685)
Simoons ML. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet 2001;357:1915-1924 (Pubitemid 32568331)
Boersma E, Akkerhuis KM, Théroux P, Califf RM, Topol EJ, Simoons ML. Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention. Circulation 1999;100:2045-2048 (Pubitemid 29532053)
Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006;295:1531-1538
Roe MT, Christenson RH, Ohman EM, et al. A randomized, placebo-controlled trial of early eptifibatide for non-ST-segment elevation acute coronary syndromes. Am Heart J 2003;146:993-998 (Pubitemid 37500772)
Stone GW, Bertrand ME, Moses JW, et al. Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing Trial. JAMA 2007;297:591-602. (Pubitemid 46257281)
Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002;359:189-198 [Erratum, Lancet 2002;359:2120.] (Pubitemid 36285576)
Pieper KS, Tsiatis AA, Davidian M, et al. Differential treatment benefit of platelet glycoprotein IIb/IIIa inhibition with percutaneous coronary intervention versus medical therapy for acute coronary syndromes: exploration of methods. Circulation 2004;109:641-646 (Pubitemid 38198872)
Bertrand ME, Simoons ML, Fox KA, et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2002;23:1809-1840 [Errata, Eur Heart J 2003;24:485, 1174-5.] (Pubitemid 35215244)
Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2002;40:1366-1374
Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997;349:1429-1435 [Erratum, Lancet 1997;350:744.]
Ndrepepa G, Kastrati A, Mehilli J, et al. One-year clinical outcomes with abciximab vs. placebo in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention after pre-treatment with clopidogrel: results of the ISAR-REACT 2 randomized trial. Eur Heart J 2008;29:455-461
Freemantle N. Interpreting the results of secondary end points and subgroup analyses in clinical trials: should we lock the crazy aunt in the attic? BMJ 2001;322:989-991
Kleiman NS, Lincoff AM, Flaker GC, et al. Early percutaneous coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. Circulation 2000;101:751-757 (Pubitemid 30100081)
Shaw LJ, Berman DS, Maron DJ, et al. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: results from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial nuclear substudy. Circulation 2008;117:1283-1291
