Multicenter Investigation of Limitation of Infarct Size (MILIS)

Summary

To assess the ability of two separate therapeutic interventions, propranolol and hyaluronidase, to limit the ultimate size of an acute myocardial infarction. A secondary objective was to assess the influence of these therapies upon ventricular function and morbidity following myocardial infarction.

Timeline

Start

1977-09

Primary completion

—

Completion

1985-12

Publications

• Background Rude RE, Poole WK, Muller JE, Turi Z, Rutherford J, Parker C, Roberts R, Raabe DS Jr, Gold HK, Stone PH, et al. Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients. Am J Cardiol. 1983 Nov 1;52(8):936-42. doi: 10.1016/0002-9149(83)90508-8.
• Background Hackel DB, Reimer KA, Ideker RE, Mikat EM, Hartwell TD, Parker CB, Braunwald EB, Buja M, Gold HK, Jaffe AS, et al. Comparison of enzymatic and anatomic estimates of myocardial infarct size in man. Circulation. 1984 Nov;70(5):824-35. doi: 10.1161/01.cir.70.5.824.
• Background Mukharji J, Rude RE, Poole WK, Gustafson N, Thomas LJ Jr, Strauss HW, Jaffe AS, Muller JE, Roberts R, Raabe DS Jr, et al. Risk factors for sudden death after acute myocardial infarction: two-year follow-up. Am J Cardiol. 1984 Jul 1;54(1):31-6. doi: 10.1016/0002-9149(84)90299-6.
• Background Roberts R, Croft C, Gold HK, Hartwell TD, Jaffe AS, Muller JE, Mullin SM, Parker C, Passamani ER, Poole WK, et al. Effect of propranolol on myocardial-infarct size in a randomized blinded multicenter trial. N Engl J Med. 1984 Jul 26;311(4):218-25. doi: 10.1056/NEJM198407263110403.
• Background Croft CH, Rude RE, Lewis SE, Parkey RW, Poole WK, Parker C, Fox N, Roberts R, Strauss HW, Thomas LJ, et al. Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: analysis of 357 patients. Am J Cardiol. 1984 Feb 1;53(4):421-8. doi: 10.1016/0002-9149(84)90006-7.
• Background Muller JE (Ed.), Braunwald E, Mock MB, et al (Assoc. Eds.): National Heart, Lung, and Blood Institute Multicenter Investigation of the Limitation of Infarct Size (MILIS). Design and Methods of the Clinical Trial. An Investigation of Beta-Blockade and Hyaluronidase for Treatment of Acute Myocardial Infarction. AHA Monograph 100:1-134, 1984.
• Background Turi ZG, Rutherford JD, Roberts R, Muller JE, Jaffe AS, Rude RE, Parker C, Raabe DS, Stone PH, Hartwell TD, et al. Electrocardiographic, enzymatic and scintigraphic criteria of acute myocardial infarction as determined from study of 726 patients (A MILIS Study). Am J Cardiol. 1985 Jun 1;55(13 Pt 1):1463-8. doi: 10.1016/0002-9149(85)90954-3.
• Background Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, Poole WK, Passamani E, Roberts R, Robertson T, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med. 1985 Nov 21;313(21):1315-22. doi: 10.1056/NEJM198511213132103.
• Background Muller JE, Turi ZG, Stone PH, Rude RE, Raabe DS, Jaffe AS, Gold HK, Gustafson N, Poole WK, Passamani E, Smith TW, Braunwald E; MILIS Study Group. Digoxin therapy and mortality after myocardial infarction. Experience in the MILIS Study. N Engl J Med. 1986 Jan 30;314(5):265-71. doi: 10.1056/NEJM198601303140501.
• Background Wheelan K, Mukharji J, Rude RE, Poole WK, Gustafson N, Thomas LJ Jr, Strauss HW, Jaffe AS, Muller JE, Roberts R, et al. Sudden death and its relation to QT-interval prolongation after acute myocardial infarction: two-year follow-up. Am J Cardiol. 1986 Apr 1;57(10):745-50. doi: 10.1016/0002-9149(86)90606-5.
• Background Rude RE, Buja LM, Willerson JT. Propranolol in acute myocardial infarction: the MILIS experience. Am J Cardiol. 1986 Apr 25;57(12):38F-42F. doi: 10.1016/0002-9149(86)90887-8.
• Background Hyaluronidase therapy for acute myocardial infarction: results of a randomized, blinded, multicenter trial. MILIS Study Group. Am J Cardiol. 1986 Jun 1;57(15):1236-43. doi: 10.1016/0002-9149(86)90195-5.
• Background Turi ZG, Stone PH, Muller JE, Parker C, Rude RE, Raabe DE, Jaffe AS, Hartwell TD, Robertson TL, Braunwald E. Implications for acute intervention related to time of hospital arrival in acute myocardial infarction. Am J Cardiol. 1986 Aug 1;58(3):203-9. doi: 10.1016/0002-9149(86)90047-0.
• Background Croft CH, Rude RE, Gustafson N, Stone PH, Poole WK, Roberts R, Strauss HW, Raabe DS Jr, Thomas LJ, Jaffe AS, et al. Abrupt withdrawal of beta-blockade therapy in patients with myocardial infarction: effects on infarct size, left ventricular function, and hospital course. Circulation. 1986 Jun;73(6):1281-90. doi: 10.1161/01.cir.73.6.1281.
• Background Lamas GA, Muller JE, Turi ZG, Stone PH, Rutherford JD, Jaffe AS, Raabe DS, Rude RE, Mark DB, Califf RM, et al. A simplified method to predict occurrence of complete heart block during acute myocardial infarction. Am J Cardiol. 1986 Jun 1;57(15):1213-9. doi: 10.1016/0002-9149(86)90191-8.
• Background Stone PH, Turi ZG, Muller JE, Parker C, Hartwell T, Rutherford JD, Jaffe AS, Raabe DS, Passamani ER, Willerson JT, et al. Prognostic significance of the treadmill exercise test performance 6 months after myocardial infarction. J Am Coll Cardiol. 1986 Nov;8(5):1007-17. doi: 10.1016/s0735-1097(86)80374-6.
• Background Tofler GH, Stone PH, Muller JE, Willich SN, Davis VG, Poole WK, Strauss HW, Willerson JT, Jaffe AS, Robertson T, et al. Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women. J Am Coll Cardiol. 1987 Mar;9(3):473-82. doi: 10.1016/s0735-1097(87)80038-4.
• Background Willich SN, Stone PH, Muller JE, Tofler GH, Crowder J, Parker C, Rutherford JD, Turi ZG, Robertson T, Passamani E, et al. High-risk subgroups of patients with non-Q wave myocardial infarction based on direction and severity of ST segment deviation. Am Heart J. 1987 Nov;114(5):1110-9. doi: 10.1016/0002-8703(87)90186-4.
• Background Cox DA, Stone PH, Muller JE, Parker C, Hartwell TD, Rutherford JD, Roberts R, Jaffe AS, Hackel DB, Passamani ER, et al. Prognostic implications of an early peak in plasma MB creatine kinase in patients with acute myocardial infarction. J Am Coll Cardiol. 1987 Nov;10(5):979-90. doi: 10.1016/s0735-1097(87)80334-0.
• Background Tofler GH, Stone PH, Muller JE, Rutherford JD, Willich SN, Gustafson NF, Poole WK, Sobel BE, Willerson JT, Robertson T, et al. Prognosis after cardiac arrest due to ventricular tachycardia or ventricular fibrillation associated with acute myocardial infarction (the MILIS Study). Multicenter Investigation of the Limitation of Infarct Size. Am J Cardiol. 1987 Oct 1;60(10):755-61. doi: 10.1016/0002-9149(87)91018-6.
• Background Stone PH, Raabe DS, Jaffe AS, Gustafson N, Muller JE, Turi ZG, Rutherford JD, Poole WK, Passamani E, Willerson JT, et al. Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location. J Am Coll Cardiol. 1988 Mar;11(3):453-63. doi: 10.1016/0735-1097(88)91517-3.
• Background Hands ME, Cook EF, Stone PH, Muller JE, Hartwell T, Sobel BE, Roberts R, Braunwald E, Rutherford JD. Electrocardiographic diagnosis of myocardial infarction in the presence of complete left bundle branch block. Am Heart J. 1988 Jul;116(1 Pt 1):23-31. doi: 10.1016/0002-8703(88)90245-1.
• Background Muller JE, Rude RE, Braunwald E, Hartwell TD, Roberts R, Sobel BE, Ritter C, Parker CB, Jaffe AS, Stone PH, et al. Myocardial infarct extension: occurrence, outcome, and risk factors in the Multicenter Investigation of Limitation of Infarct Size. Ann Intern Med. 1988 Jan;108(1):1-6. doi: 10.7326/0003-4819-108-1-1.
• Background Roberts R, Braunwald E, Muller JE, Croft C, Gold HK, Hartwell TD, Jaffe AS, Mullin SM, Parker C, Passamani ER, et al. Effect of hyaluronidase on mortality and morbidity in patients with early peaking of plasma creatine kinase MB and non-transmural ischaemia. Multicentre investigation for the limitation of infarct size (MILIS). Br Heart J. 1988 Oct;60(4):290-8. doi: 10.1136/hrt.60.4.290.
• Background Lee RT, Lee TH, Poole WK, Gustafson N, Stone PH, Jaffe AS, Muller JE, Sobel BE, Roberts R, Braunwald E. Rate of disappearance of creatine kinase-MB after acute myocardial infarction: clinical determinants of variability. Am Heart J. 1988 Dec;116(6 Pt 1):1493-9. doi: 10.1016/0002-8703(88)90734-x.
• Background Tofler GH, Muller JE, Stone PH, Willich SN, Davis VG, Poole WK, Robertson T, Braunwald E. Pericarditis in acute myocardial infarction: characterization and clinical significance. Am Heart J. 1989 Jan;117(1):86-92. doi: 10.1016/0002-8703(89)90660-1.
• Background Pohjola-Sintonen S, Muller JE, Stone PH, Willich SN, Antman EM, Davis VG, Parker CB, Braunwald E. Ventricular septal and free wall rupture complicating acute myocardial infarction: experience in the Multicenter Investigation of Limitation of Infarct Size. Am Heart J. 1989 Apr;117(4):809-18. doi: 10.1016/0002-8703(89)90617-0.
• Background Hands ME, Rutherford JD, Muller JE, Davies G, Stone PH, Parker C, Braunwald E. The in-hospital development of cardiogenic shock after myocardial infarction: incidence, predictors of occurrence, outcome and prognostic factors. The MILIS Study Group. J Am Coll Cardiol. 1989 Jul;14(1):40-6; discussion 47-8. doi: 10.1016/0735-1097(89)90051-x.
• Background Stone PH, Muller JE, Hartwell T, York BJ, Rutherford JD, Parker CB, Turi ZG, Strauss HW, Willerson JT, Robertson T, et al. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. The MILIS Study Group. J Am Coll Cardiol. 1989 Jul;14(1):49-57. doi: 10.1016/0735-1097(89)90053-3.
• Background Tofler GH, Stone PH, Muller JE, Braunwald E. Mortality for women after acute myocardial infarction: MILIS Study Group. Am J Cardiol. 1989 Jul 15;64(3):256. doi: 10.1016/0002-9149(89)90476-1. No abstract available.
• Background Barzilai B, Davis VG, Stone PH, Jaffe AS. Prognostic significance of mitral regurgitation in acute myocardial infarction. The MILIS Study Group. Am J Cardiol. 1990 May 15;65(18):1169-75. doi: 10.1016/0002-9149(90)90968-7.
• Background Tofler GH, Stone PH, Maclure M, Edelman E, Davis VG, Robertson T, Antman EM, Muller JE. Analysis of possible triggers of acute myocardial infarction (the MILIS study). Am J Cardiol. 1990 Jul 1;66(1):22-7. doi: 10.1016/0002-9149(90)90729-k.
• Background Brezinski D, Stone PH, Muller JE, Tofler GH, Davis V, Parker C, Hartley LH, Braunwald E. Prognostic significance of the Karnofsky Performance Status score in patients with acute myocardial infarction: comparison with the left ventricular ejection fraction and the exercise treadmill test performance. The MILIS Study Group. Am Heart J. 1991 May;121(5):1374-81. doi: 10.1016/0002-8703(91)90141-4.
• Background Tofler GH, Muller JE, Stone PH, Davies G, Davis VG, Braunwald E. Comparison of long-term outcome after acute myocardial infarction in patients never graduated from high school with that in more educated patients. Multicenter Investigation of the Limitation of Infarct Size (MILIS). Am J Cardiol. 1993 May 1;71(12):1031-5. doi: 10.1016/0002-9149(93)90568-w.
• Background Kloner RA, Muller J, Davis V. Effects of previous angina pectoris in patients with first acute myocardial infarction not receiving thrombolytics. MILIS Study Group. Multicenter Investigation of the Limitation of Infarct Size. Am J Cardiol. 1995 Mar 15;75(8):615-7. doi: 10.1016/s0002-9149(99)80628-6. No abstract available.
• Background Mullin SM, Warwick S, Akers M, Beecher P, Helminger K, Moses B, Rigby PA, Taplin NE, Werner W, Wettach R. An acute intervention trial: the research nurse coordinator's role. Control Clin Trials. 1984 Jun;5(2):141-56. doi: 10.1016/0197-2456(84)90120-x.

Drugs

Indications