From the Istituto di Ricerche Farmacologiche "Mario Negri,"
Milan, Italy.
Correspondence to Dr Maria Grazia Franzosi, ACE Inhibitor Collaborative Group, GISSI Coordinating Centre, Istituto di Ricerche Farmacologiche "Mario Negri," Via Eritrea 62, 20157 Milano, Italy. E-mail depcardio{at}irfmn.mnegri.it
Background—Several large-scale
trials have demonstrated improved survival with
ACE-inhibitor therapy started during acute myocardial
infarction. A systematic overview was conducted to resolve
uncertainties regarding time of initiation, time course of effect, and
identification of patients in whom the benefits or the risks may
be greater.
Methods and Results—This overview aimed to include individual
data from all randomized trials involving more than 1000 patients in
which ACE-inhibitor treatment was started in the acute
phase (0 to 36 hours) of myocardial infarction and continued for a
short time (4 to 6 weeks). Data were available for 98 496 patients
from 4 eligible trials, and the results were consistent among
the trials. Thirty-day mortality was 7.1% among patients allocated to
ACE inhibitors and 7.6% among control subjects,
corresponding to a 7% (SD, 2%) proportional reduction (95% CI, 2%
to 11%; 2P<0.004). This represented
avoidance of
Conclusions—These results support the use of ACE
inhibitors early in the treatment of acute MI, either to a
wide range of patients or selectively in patients with anterior MI and
in those at increased risk of death.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Indications for ACE Inhibitors in the Early Treatment of Acute Myocardial Infarction
Systematic Overview of Individual Data From 100 000 Patients in Randomized Trials
5 (SD, 2) deaths per 1000 patients, with most of the
benefit observed within the first week. The proportional benefit was
similar in patients at different underlying risk. The absolute benefit
was particularly large in some high-risk groups (ie, Killip class 2 to
3, heart rate 
100 bpm at entry) and in anterior MI.
ACE-inhibitor therapy also reduced the incidence of
nonfatal cardiac failure (14.6% versus 15.2%, 2P=0.01)
but was associated with an excess of persistent hypotension (17.6%
versus 9.3%, 2P<0.01) and renal dysfunction (1.3%
versus 0.6%, 2P<0.01).
Key Words: ACE inhibitors • myocardial infarction • trials • systematic overview
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J. H. O'Keefe, M. Wetzel, R. R. Moe, K. Brosnahan, and C. J. Lavie Should an angiotensin-converting enzyme inhibitor be standard therapy for patients with atherosclerotic disease? J. Am. Coll. Cardiol., January 1, 2001; 37(1): 1 - 8. [Abstract] [Full Text] [PDF]
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Q.-G. Xia, O. Chung, H. Spitznagel, S. Illner, G. Janichen, B. Rossius, P. Gohlke, and T. Unger Significance of timing of angiotensin AT1 receptor blockade in rats with myocardial infarction-induced heart failure Cardiovasc Res, January 1, 2001; 49(1): 110 - 117. [Abstract] [Full Text] [PDF]
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H. Oxenham and N. Sharpe Angiotensin-converting enzyme inhibitor treatment after myocardial infarction: A selective approach for maximum benefit J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2054 - 2055. [Full Text] [PDF]
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W. J. Rogers, J. G. Canto, C. T. Lambrew, A. J. Tiefenbrunn, B. Kinkaid, D. A. Shoultz, P. D. Frederick, N. Every, and for the Investigators in the National Registry of Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the U.S. from 1990 through 1999: The National Registry of Myocardial Infarction 1, 2 and 3 J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2056 - 2063. [Abstract] [Full Text] [PDF]
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S. E WIEGERS and M. S. J. SUTTON When should ACE inhibitors or warfarin be discontinued after myocardial infarction? Heart, October 1, 2000; 84(4): 361 - 362. [Full Text]
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W. S. Waring Early initiation of ACE inhibitor treatment after acute myocardial infarction - a missed therapeutic opportunity? Journal of Renin-Angiotensin-Aldosterone System, September 1, 2000; 1(3): 245 - 251. [PDF]
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A. P Maggioni Secondary prevention: improving outcomes following myocardial infarction Heart, September 1, 2000; 84(90001): 5i - 7. [Full Text]
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A. Cargnoni, C. Ceconi, P. Bernocchi, A. Boraso, G. Parrinello, S. Curello, and R. Ferrari Reduction of oxidative stress by carvedilol: role in maintenance of ischaemic myocardium viability Cardiovasc Res, August 18, 2000; 47(3): 556 - 566. [Abstract] [Full Text] [PDF]
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R. Latini, G. Tognoni, A. P. Maggioni, C. Baigent, E. Braunwald, Z.-M. Chen, R. Collins, M. Flather, M. Franzosi, J. Kjekshus, et al. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: Systematic overview of individual data from 96,712 randomized patients J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1801 - 1807. [Abstract] [Full Text] [PDF]
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C. Torp-Pedersen and L. Kober Prolongation of life with angiotensin converting enzyme inhibitor therapy. Eur. Heart J., April 2, 2000; 21(8): 597 - 598. [PDF]
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J. Muntwyler and T.F. Luscher Assessment of cardiovascular risk: time to apply genetic risk factors? Eur. Heart J., April 2, 2000; 21(8): 611 - 613. [PDF]
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W. J. Rogers, J. G. Canto, H. V. Barron, J. A. Boscarino, D. A. Shoultz, N. R. Every, and for the Investigators in the National Registry of Treatment and outcome of myocardial infarction in hospitals with and without invasive capability J. Am. Coll. Cardiol., February 1, 2000; 35(2): 371 - 379. [Abstract] [Full Text] [PDF]
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D. W. O'Brien, Y. Xu, V. Menon, and B. I. Jugdutt Efficacy of Pretreatment With the Angiotensin II Type 1 Receptor Blocker UP269-6 and Losartan in the Dog: Effect on Hemodynamics and Ischemia-Reperfusion Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(2): 129 - 137. [Abstract] [PDF]
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R. D. Feldman, N. Campbell, P. Larochelle, P. Bolli, E. D. Burgess, S. G. Carruthers, J. S. Floras, R. B. Haynes, G. Honos, F. H.H. Leenen, et al. 1999 Canadian recommendations for the management of hypertension Can. Med. Assoc. J., December 14, 1999; 161(90120): S1 - 17. [Abstract] [Full Text] [PDF]
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V. Gaussin and M. D. Schneider Surviving Infarction One Gene at a Time : Decreased Remodeling and Mortality in Engineered Mice Lacking the Angiotensin II Type 1A Receptor Circulation, November 16, 1999; 100(20): 2043 - 2044. [Full Text] [PDF]
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M. A. Leesar, M. F. Stoddard, S. Manchikalapudi, and R. Bolli Bradykinin-induced preconditioning in patients undergoing coronary angioplasty J. Am. Coll. Cardiol., September 1, 1999; 34(3): 639 - 650. [Abstract] [Full Text] [PDF]
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J. K. French, D. J. Amos, B. F. Williams, D. B. Cross, J. M. Elliott, H. H. Hart, M. G. Williams, R. M. Norris, N. G. Ashton, R. M. L. Whitlock, et al. Effects of early captopril administration after thrombolysis on regional wall motion in relation to infarct artery blood flow J. Am. Coll. Cardiol., January 1, 1999; 33(1): 139 - 145. [Abstract] [Full Text] [PDF]
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S. KAUL Myocardial contrast echocardiography in acute myocardial infarction: time to test for routine clinical use? Heart, January 1, 1999; 81(1): 2 - 5. [Full Text]
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C. J. Pepine, E. Handberg-Thurmond, R. G. Marks, M. Conlon, R. Cooper-Dehoff, P. Volkers, P. Zellig, and for The INVEST Investigators Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1228 - 1237. [Abstract] [Full Text] [PDF]
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