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Long-term treatment with metoprolol after myocardial infarction: Effect on 3 year mortality and morbidity FREE

Gunnar Olsson, MD; Nina Rehnqvist, MD, PhD; Andreas Sjögren, MD, PhD; Leif Erhardt, MD, PhD; Torbjörn Lundman, MD, PhD
[+] Author Information

From the Department of Medicine, Karolinska Institute, Danderyd Hospital, Danderyd, Sweden.

Address for reprints: Gunnar Olsson, MD, Department of Medicine, Danderyd Hospital, S-182 88 Danderyd, Sweden.

American College of Cardiology Foundation

J Am Coll Cardiol. 1985;5(6):1428-1437. doi:10.1016/S0735-1097(85)80360-0
Published online

  The effects of metoprolol treatment in patients surviving acute myocardial infarction have been investigated in a double-blind randomized study. The patients were stratified according to age, infarct size and type of ventricular arrhythmias before administration of metoprolol, 100 mg twice daily (n = 154), or placebo (n = 147). All patients were followed up for 36 months. There were 31 (29 cardiac) and 25 (20 cardiac) deaths in the placebo and metoprolol groups, respectively. Subgroup analyses showed a significant reduction of cardiac death in patients with a large infarct (32.1% with placebo versus 12.5% with metoprolol, p < 0.05) as a result of active treatment.Sudden death rates were 14.7% in the placebo versus 5.8% in the metoprolol group (p < 0.05). The incidence of nonfatal reinfarction was 21.1% in the placebo versus 11.7% in the metoprolol group (p < 0.05). The reduction in nonfatal reinfarction was similar in all pretreatment risk strata. The difference between the two groups in cumulative number of cardiac deaths and patients experiencing nonfatal reinfarction increased throughout the study. Furthermore, cerebrovascular events (p < 0.05) and coronary bypass surgery (p = 0.058) were more frequent in the placebo group.In conclusion, after 36 months of metoprolol treatment after myocardial infarction, there was a significant reduction of nonfatal reinfarction and sudden death in all patients and a reduction of cardiac death in those with a large infarct.

References

Snow  PJD; Effect of propranolol in myocardial infarction. Lancet. 2 1965:551-553.
CrossRef | PubMed
Wilhelmsson  C, Vedin  JA, Wilhelmsen  L, Tibblin  G, Werkö  L; Reduction of sudden deaths after myocardial infarction by treatment with alprenolol. Lancet. 2 1974:1157-1160.
CrossRef | PubMed
Ahlmark  G, Saetre  H, Korsgren  M; Reduction of sudden deaths after myocardial infarction (letter). Lancet. 2 1974:1563
CrossRef | PubMed
 A Multicenter International Study. Improvement in prognosis of myocardial infarction by long-term beta-adrenoceptor blockade using prac-tolol. Br Med J. 3 1975:735-740.
CrossRef | PubMed
Hampton  JR; Should every survivor of a heart attack be given a beta-blocker? Part I. Evidence from clinical trials. Br Med J. 285 1982:33-36.
CrossRef
Breckenridge  A; Should every survivor of a heart attack be given a beta-blocker? Part II. Evidence from a clinical pharmacological standpoint. Br Med J. 285 1982:37-39.
CrossRef
Helmers  C; Short and long-term prognostic indices in acute myocardial infarction. Acta Med Scand. 555 (suppl) 1974:1-86.
Rehnqvist  N; Ventricular arrhythmias after an acute myocardial infarction. Prognostic weight and natural history. Eur J Cardiol. 7 1978:169-187.
PubMed
The Norwegian Multicenter Study Group Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med. 304 1981:801-807.
CrossRef | PubMed
Beta-Blocker Heart Attack Trial Research Group A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA. 247 1982:1707-1714.
CrossRef | PubMed
Hjalmarsson  Å, Herlitz  J, Malek  I; Effect on mortality of me-toprolol in acute myocardial infarction. Lancet. 2 1981:823-827.
CrossRef | PubMed
Rehnqvist  N; Ventricular arrhythmias prior to discharge after acute myocardial infarction. Eur J Cardiol. 4 1976:63-70.
PubMed
Erhardt  LR; Clinical and pathological observations in different types of acute myocardial infarction. Acta Med Scand. 560 (suppl) 1974:1-78.
Scandinavian Committee on Enzymes Recommended methods for the determination of four enzymes in blood. Scand J Clin Lab Invest. 33 1974:291-306.
CrossRef | PubMed
Brydon  WG, Smith  AF; An appraisal of routine methods for the determination of the anodal isoenzymes of lactate dehydrogenase. Clin Chim Acta. 43 1973:361-369.
CrossRef | PubMed
Olsson  G, Hjemdahl  P, Rehnqvist  N; Rebound phenomena following gradual withdrawal of chronic metoprolol treatment in patients with ischemic heart disease. Am Heart J. 108 1984:454-462.
CrossRef | PubMed
Olsson  G, Rehnqvist  N; Ventricular arrhythmias during the first year after acute myocardial infarction: influence of long-term treatment with propranolol. Circulation. 69 1984:1129-1134.
CrossRef | PubMed
Olsson  G, Rehnqvist  N, Lundman  T, Melcher  A; Metoprolol treatment after acute myocardial infarction. Effects on ventricular arrhythmias and exercise tests during 6 months. Acta Med Scand. 210 1981:59-65.
CrossRef | PubMed
Herlitz  J, Hjalmarsson  Å, Waldenström  J; Relationship between en-zymatically estimated infarct size and short- and long-term survival after acute myocardial infarction. Acta Med Scand. 216 1984:261-267.
CrossRef | PubMed
Sobel  BE, Bresnahan  GF, Shell  WE, Yoder  RD; Estimation of infarct size in man and its relation to prognosis. Circulation. 46 1972:640-648.
CrossRef | PubMed
Freiman  JA, Chalmers  TC, Smith  H  Jr, Kuebler  RR; The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trials: survey of 71 “negative” trials. N Engl J Med. 299 1978:690-694.
CrossRef | PubMed
Hansteen  V, Møinichen  E, Lorentsen  E; One year's treatment with propranolol after myocardial infarction: preliminary report of Norwegian multicenter trial. Br Med J. 284 1982:155-160.
CrossRef
Andersen  MP, Bechsgaard  P, Frederiksen  J; Effect of alprenolol on mortality among patients with definite or suspected acute myocardial infarction. Preliminary report. Lancet. 2 1979:865-872.
CrossRef | PubMed
Gundersen  T, Abrahamsen  AM, Kjekshus  J, Rønnevik  PK; Timolol-related reduction in mortality and reinfarction in patients ages 65–75 years surviving acute myocardial infarction. Circulation. 66 1982:1179-1184.
CrossRef | PubMed
Hawkins  CM, Richardson  DW, Vokonas  PS; Effect of propranolol in reducing mortality in older myocardial infarction patients. The beta-blocker heart attack trial experience. Circulation. 67 (suppl I) 1983:I-94-I-97.
Rehnqvist  N, Lundman  T, Sjögren  A; Prognostic implications of ventricular arrhythmias registered before discharge and one year after acute myocardial infarction. Acta Med Scand. 204 1978:203-209.
CrossRef | PubMed
Rydén  L, Ariniego  R, Amman  K; A double-blind trial of metoprolol in acute myocardial infarction: effects on ventricular tachyarrhythmias. N Engl J Med. 308 1983:614-618.
CrossRef | PubMed
Julian  DG, Jackson  FS, Prescott  RJ, Szekely  P; Controlled trial of Sotalol for one year after myocardial infarction. Lancet. 1 1982:1142-1147.
CrossRef | PubMed
Tasgal  J, Vaughan Williams  EM; The effect of prolonged propranolol administration on myocardial transmural capillary density in young rabbits. J Physiol. 315 1981:353-367.
PubMed
Campbell  WB, Callahan  KS, Johnson  AR, Graham  RM; Antiplatelet activity of beta-adrenergic antagonists: inhibition of thromboxane syn- thesis and platelet aggregation in patients receiving long-term propranolol treatment. Lancet. 2 1981:1382-1384.
CrossRef | PubMed
Leren  P, Helgeland  A, Holme  I, Foss  PO, Hjermann  I, Lund-Johansen  PG; Effect of propranolol and prazosin on blood lipids. The Oslo Study. Lancet. 2 1981:4-6.
PubMed
Shulman  RS, Herbert  PN, Capone  RJ; Effects of propranolol on blood lipids and lipoproteins in myocardial infarction. Circulation. 67 (suppl I) 1983:I-19-I-21.

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References

Snow  PJD; Effect of propranolol in myocardial infarction. Lancet. 2 1965:551-553.
CrossRef | PubMed
Wilhelmsson  C, Vedin  JA, Wilhelmsen  L, Tibblin  G, Werkö  L; Reduction of sudden deaths after myocardial infarction by treatment with alprenolol. Lancet. 2 1974:1157-1160.
CrossRef | PubMed
Ahlmark  G, Saetre  H, Korsgren  M; Reduction of sudden deaths after myocardial infarction (letter). Lancet. 2 1974:1563
CrossRef | PubMed
 A Multicenter International Study. Improvement in prognosis of myocardial infarction by long-term beta-adrenoceptor blockade using prac-tolol. Br Med J. 3 1975:735-740.
CrossRef | PubMed
Hampton  JR; Should every survivor of a heart attack be given a beta-blocker? Part I. Evidence from clinical trials. Br Med J. 285 1982:33-36.
CrossRef
Breckenridge  A; Should every survivor of a heart attack be given a beta-blocker? Part II. Evidence from a clinical pharmacological standpoint. Br Med J. 285 1982:37-39.
CrossRef
Helmers  C; Short and long-term prognostic indices in acute myocardial infarction. Acta Med Scand. 555 (suppl) 1974:1-86.
Rehnqvist  N; Ventricular arrhythmias after an acute myocardial infarction. Prognostic weight and natural history. Eur J Cardiol. 7 1978:169-187.
PubMed
The Norwegian Multicenter Study Group Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med. 304 1981:801-807.
CrossRef | PubMed
Beta-Blocker Heart Attack Trial Research Group A randomized trial of propranolol in patients with acute myocardial infarction. I. Mortality results. JAMA. 247 1982:1707-1714.
CrossRef | PubMed
Hjalmarsson  Å, Herlitz  J, Malek  I; Effect on mortality of me-toprolol in acute myocardial infarction. Lancet. 2 1981:823-827.
CrossRef | PubMed
Rehnqvist  N; Ventricular arrhythmias prior to discharge after acute myocardial infarction. Eur J Cardiol. 4 1976:63-70.
PubMed
Erhardt  LR; Clinical and pathological observations in different types of acute myocardial infarction. Acta Med Scand. 560 (suppl) 1974:1-78.
Scandinavian Committee on Enzymes Recommended methods for the determination of four enzymes in blood. Scand J Clin Lab Invest. 33 1974:291-306.
CrossRef | PubMed
Brydon  WG, Smith  AF; An appraisal of routine methods for the determination of the anodal isoenzymes of lactate dehydrogenase. Clin Chim Acta. 43 1973:361-369.
CrossRef | PubMed
Olsson  G, Hjemdahl  P, Rehnqvist  N; Rebound phenomena following gradual withdrawal of chronic metoprolol treatment in patients with ischemic heart disease. Am Heart J. 108 1984:454-462.
CrossRef | PubMed
Olsson  G, Rehnqvist  N; Ventricular arrhythmias during the first year after acute myocardial infarction: influence of long-term treatment with propranolol. Circulation. 69 1984:1129-1134.
CrossRef | PubMed
Olsson  G, Rehnqvist  N, Lundman  T, Melcher  A; Metoprolol treatment after acute myocardial infarction. Effects on ventricular arrhythmias and exercise tests during 6 months. Acta Med Scand. 210 1981:59-65.
CrossRef | PubMed
Herlitz  J, Hjalmarsson  Å, Waldenström  J; Relationship between en-zymatically estimated infarct size and short- and long-term survival after acute myocardial infarction. Acta Med Scand. 216 1984:261-267.
CrossRef | PubMed
Sobel  BE, Bresnahan  GF, Shell  WE, Yoder  RD; Estimation of infarct size in man and its relation to prognosis. Circulation. 46 1972:640-648.
CrossRef | PubMed
Freiman  JA, Chalmers  TC, Smith  H  Jr, Kuebler  RR; The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trials: survey of 71 “negative” trials. N Engl J Med. 299 1978:690-694.
CrossRef | PubMed
Hansteen  V, Møinichen  E, Lorentsen  E; One year's treatment with propranolol after myocardial infarction: preliminary report of Norwegian multicenter trial. Br Med J. 284 1982:155-160.
CrossRef
Andersen  MP, Bechsgaard  P, Frederiksen  J; Effect of alprenolol on mortality among patients with definite or suspected acute myocardial infarction. Preliminary report. Lancet. 2 1979:865-872.
CrossRef | PubMed
Gundersen  T, Abrahamsen  AM, Kjekshus  J, Rønnevik  PK; Timolol-related reduction in mortality and reinfarction in patients ages 65–75 years surviving acute myocardial infarction. Circulation. 66 1982:1179-1184.
CrossRef | PubMed
Hawkins  CM, Richardson  DW, Vokonas  PS; Effect of propranolol in reducing mortality in older myocardial infarction patients. The beta-blocker heart attack trial experience. Circulation. 67 (suppl I) 1983:I-94-I-97.
Rehnqvist  N, Lundman  T, Sjögren  A; Prognostic implications of ventricular arrhythmias registered before discharge and one year after acute myocardial infarction. Acta Med Scand. 204 1978:203-209.
CrossRef | PubMed
Rydén  L, Ariniego  R, Amman  K; A double-blind trial of metoprolol in acute myocardial infarction: effects on ventricular tachyarrhythmias. N Engl J Med. 308 1983:614-618.
CrossRef | PubMed
Julian  DG, Jackson  FS, Prescott  RJ, Szekely  P; Controlled trial of Sotalol for one year after myocardial infarction. Lancet. 1 1982:1142-1147.
CrossRef | PubMed
Tasgal  J, Vaughan Williams  EM; The effect of prolonged propranolol administration on myocardial transmural capillary density in young rabbits. J Physiol. 315 1981:353-367.
PubMed
Campbell  WB, Callahan  KS, Johnson  AR, Graham  RM; Antiplatelet activity of beta-adrenergic antagonists: inhibition of thromboxane syn- thesis and platelet aggregation in patients receiving long-term propranolol treatment. Lancet. 2 1981:1382-1384.
CrossRef | PubMed
Leren  P, Helgeland  A, Holme  I, Foss  PO, Hjermann  I, Lund-Johansen  PG; Effect of propranolol and prazosin on blood lipids. The Oslo Study. Lancet. 2 1981:4-6.
PubMed
Shulman  RS, Herbert  PN, Capone  RJ; Effects of propranolol on blood lipids and lipoproteins in myocardial infarction. Circulation. 67 (suppl I) 1983:I-19-I-21.

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