THE REOPEN-AMI STUDY - Intracoronary Nitroprusside Versus Adenosine in Acute Myocardial Infarction

Summary

The occurrence of no-reflow phenomenon after recanalization of the infarct related artery in acute myocardial infarction is described in up to 40% of cases. This event is associated with a worse prognosis at follow up and an unfavourable left ventricular remodelling . Two main pathogenetic mechanisms cause no-reflow: distal embolization and ischemia-reperfusion injury. Due to the multifactorial pathogenesis of no-reflow during acute MI a combined mechanic and pharmacologic approach is believed to offer a better solution for achieving optimal microvascular reperfusion. Thus, in this randomized study we will assess the effect of nitroprusside or adenosine in adjunct to current best therapy (thrombus aspiration and IIb-IIIa antagonists) for ST elevation MI using ST segment resolution on standard 12 leads ECG as primary endpoint of myocardial reperfusion.

Timeline

Start

2008-01

Primary completion

2011-06

Completion

2011-09

Publications

• Background Ito H, Okamura A, Iwakura K, Masuyama T, Hori M, Takiuchi S, Negoro S, Nakatsuchi Y, Taniyama Y, Higashino Y, Fujii K, Minamino T. Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction. Circulation. 1996 Jun 1;93(11):1993-9. doi: 10.1161/01.cir.93.11.1993.
• Background Ito H, Tomooka T, Sakai N, Yu H, Higashino Y, Fujii K, Masuyama T, Kitabatake A, Minamino T. Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation. 1992 May;85(5):1699-705. doi: 10.1161/01.cir.85.5.1699.
• Background Rezkalla SH, Kloner RA. No-reflow phenomenon. Circulation. 2002 Feb 5;105(5):656-62. doi: 10.1161/hc0502.102867. No abstract available.
• Background Henriques JP, Zijlstra F, Ottervanger JP, de Boer MJ, van 't Hof AW, Hoorntje JC, Suryapranata H. Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction. Eur Heart J. 2002 Jul;23(14):1112-7. doi: 10.1053/euhj.2001.3035.
• Background Reffelmann T, Kloner RA. The no-reflow phenomenon: A basic mechanism of myocardial ischemia and reperfusion. Basic Res Cardiol. 2006 Sep;101(5):359-72. doi: 10.1007/s00395-006-0615-2.
• Background Burzotta F, Trani C, Romagnoli E, Mazzari MA, Rebuzzi AG, De Vita M, Garramone B, Giannico F, Niccoli G, Biondi-Zoccai GG, Schiavoni G, Mongiardo R, Crea F. Manual thrombus-aspiration improves myocardial reperfusion: the randomized evaluation of the effect of mechanical reduction of distal embolization by thrombus-aspiration in primary and rescue angioplasty (REMEDIA) trial. J Am Coll Cardiol. 2005 Jul 19;46(2):371-6. doi: 10.1016/j.jacc.2005.04.057.
• Background Stone GW, Webb J, Cox DA, Brodie BR, Qureshi M, Kalynych A, Turco M, Schultheiss HP, Dulas D, Rutherford BD, Antoniucci D, Krucoff MW, Gibbons RJ, Jones D, Lansky AJ, Mehran R; Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris (EMERALD) Investigators. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial. JAMA. 2005 Mar 2;293(9):1063-72. doi: 10.1001/jama.293.9.1063.
• Background Cura FA, Escudero AG, Berrocal D, Mendiz O, Trivi MS, Fernandez J, Palacios A, Albertal M, Piraino R, Riccitelli MA, Gruberg L, Ballarino M, Milei J, Baeza R, Thierer J, Grinfeld L, Krucoff M, O'Neill W, Belardi J; PREMIAR Investigators. Protection of Distal Embolization in High-Risk Patients with Acute ST-Segment Elevation Myocardial Infarction (PREMIAR). Am J Cardiol. 2007 Feb 1;99(3):357-63. doi: 10.1016/j.amjcard.2006.08.038. Epub 2006 Dec 13.
• Background Burzotta F, Testa L, Giannico F, Biondi-Zoccai GG, Trani C, Romagnoli E, Mazzari M, Mongiardo R, Siviglia M, Niccoli G, De Vita M, Porto I, Schiavoni G, Crea F. Adjunctive devices in primary or rescue PCI: a meta-analysis of randomized trials. Int J Cardiol. 2008 Jan 24;123(3):313-21. doi: 10.1016/j.ijcard.2006.12.018. Epub 2007 Mar 26.
• Background Chaitman BR, Lim MJ. No reflow and the quest to achieve optimal perfusion during the acute phase of myocardial infarction. J Am Coll Cardiol. 2004 Jul 21;44(2):313-5. doi: 10.1016/j.jacc.2004.04.020. No abstract available.
• Background Hillegass WB, Dean NA, Liao L, Rhinehart RG, Myers PR. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol. 2001 Apr;37(5):1335-43. doi: 10.1016/s0735-1097(01)01138-x.
• Background Marzilli M, Orsini E, Marraccini P, Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation. 2000 May 9;101(18):2154-9. doi: 10.1161/01.cir.101.18.2154.
• Background Ota S, Nishikawa H, Takeuchi M, Nakajima K, Nakamura T, Okamoto S, Setsuda M, Makino K, Yamakado T, Nakano T. Impact of nicorandil to prevent reperfusion injury in patients with acute myocardial infarction: Sigmart Multicenter Angioplasty Revascularization Trial (SMART). Circ J. 2006 Sep;70(9):1099-104. doi: 10.1253/circj.70.1099.
• Background Amit G, Cafri C, Yaroslavtsev S, Fuchs S, Paltiel O, Abu-Ful A, Weinstein JM, Wolak A, Ilia R, Zahger D. Intracoronary nitroprusside for the prevention of the no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. A randomized, double-blind, placebo-controlled clinical trial. Am Heart J. 2006 Nov;152(5):887.e9-14. doi: 10.1016/j.ahj.2006.05.010.
• Background Pasceri V, Pristipino C, Pelliccia F, Granatelli A, Speciale G, Roncella A, Pironi B, Capasso M, Richichi G. Effects of the nitric oxide donor nitroprusside on no-reflow phenomenon during coronary interventions for acute myocardial infarction. Am J Cardiol. 2005 Jun 1;95(11):1358-61. doi: 10.1016/j.amjcard.2005.01.082.
• Background Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW; AMISTAD-II Investigators. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol. 2005 Jun 7;45(11):1775-80. doi: 10.1016/j.jacc.2005.02.061.
• Background TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med. 1985 Apr 4;312(14):932-6. doi: 10.1056/NEJM198504043121437. No abstract available.
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• Background Gibson CM, de Lemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, Antman EM, Braunwald E; TIMI Study Group. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation. 2001 May 29;103(21):2550-4. doi: 10.1161/01.cir.103.21.2550.
• Background Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol. 1985 Mar;5(3):587-92. doi: 10.1016/s0735-1097(85)80380-6.
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• Background Schroder R, Dissmann R, Bruggemann T, Wegscheider K, Linderer T, Tebbe U, Neuhaus KL. Extent of early ST segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction. J Am Coll Cardiol. 1994 Aug;24(2):384-91. doi: 10.1016/0735-1097(94)90292-5.
• Background Galiuto L, Garramone B, Burzotta F, Lombardo A, Barchetta S, Rebuzzi AG, Crea F; REMEDIA Investigators. Thrombus aspiration reduces microvascular obstruction after primary coronary intervention: a myocardial contrast echocardiography substudy of the REMEDIA Trial. J Am Coll Cardiol. 2006 Oct 3;48(7):1355-60. doi: 10.1016/j.jacc.2006.05.059. Epub 2006 Sep 14.
• Background Bolognese L, Carrabba N, Parodi G, Santoro GM, Buonamici P, Cerisano G, Antoniucci D. Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation. 2004 Mar 9;109(9):1121-6. doi: 10.1161/01.CIR.0000118496.44135.A7. Epub 2004 Feb 16.
• Background Bolognese L, Cerisano G, Buonamici P, Santini A, Santoro GM, Antoniucci D, Fazzini PF. Influence of infarct-zone viability on left ventricular remodeling after acute myocardial infarction. Circulation. 1997 Nov 18;96(10):3353-9. doi: 10.1161/01.cir.96.10.3353.

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