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ARTICLE |

Comparisons of Characteristics and Outcomes Among Women and Men With Acute Myocardial Infarction Treated With Thrombolytic Therapy FREE

W. Douglas Weaver, MD; Harvey D. White, MB; Robert G. Wilcox, MD; Philip E. Aylward, MD; Douglas Morris, MD; Alan Guerci, MD; E. Magnus Ohman, MD; Gabriel I. Barbash, MD; Amadeo Betriu, MD; Zygmunt Sadowski, MD; Eric J. Topol, MD; Robert M. Califf, MD
[+] Author Affiliations

For a complete list of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) investigators, see N Engl J Med. 1993;329:673-682.

Reprint requests to MITI Coordinating Center, Division of Cardiology RG-22, University of Washington, 1910 Fairview Ave E, Suite 205, Seattle, WA 98102 (Dr Weaver).


JAMA. 1996;275(10):777-782. doi:10.1001/jama.1996.03530340041027
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Published online

Objective.  —To compare baseline characteristics, complications, and treatment-specific outcomes of women and men with acute myocardial infarction treated with thrombolytic therapy.

Design.  —Randomized controlled trial.

Patients and Setting.  —A total of 10315 women and 30706 men with acute myocardial infarction treated in 1081 hospitals in 15 countries as part of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I).

Intervention.  —One of four thrombolytic regimens: (1) streptokinase with subcutaneous heparin; (2) streptokinase with intravenous heparin; (3) streptokinase plus alteplase (tissue-type plasminogen activator) with intravenous heparin; or (4) accelerated alteplase with intravenous heparin.

Main Outcome Measures.  —Mortality, stroke, and nonfatal complications during 30-day follow-up.

Results.  —Women were on average 7 years older than men and delayed 18 minutes (median) longer after symptom onset before presenting to the hospital. After adjustment for age, women more often had a history of diabetes, hypertension, and smoking than men. Time to treatment was significantly longer in women (1.2 vs 1.0 hours; P<.001). Women had more nonfatal complications after treatment, including shock (9% vs 5%; P<.001), congestive heart failure (22% vs 14%; P<.001), serious bleeding (15% vs 7%; P<.001), and reinfarction (5.1% vs 3.6%; P<.001). Women had twice as many total strokes as men (2.1% vs 1.2%; P<.001), secondary to their older age at presentation. The unadjusted mortality rate was twice as high in women as men (11.3% vs 5.5%; P<.001); the relative risk (RR) of death was greater among women than men after adjustment for differences in baseline characteristics (RR=1.15; 95% confidence interval, 1.0 to 1.31). Although women and men underwent angiography at similar rates, there were small but significant differences in their rates of revascularization procedures (angioplasty: 35% of women and 32% of men; bypass surgery: 7% of women and 9% of men; P<.001 for both). The higher rate of stroke in women after treatment with alteplase (2.0% vs 1.9% with streptokinase and intravenous heparin) was offset by a greater relative reduction in mortality (10.3% vs 11.1%).

Conclusion.  —Women who received thrombolytic therapy for treatment of acute myocardial infarction were at greater risk for both fatal and nonfatal complications than men.(JAMA. 1996;275:777-782)

REFERENCES

Maynard C, Litwin PE, Martin JS, Weaver WD.  Gender differences in the treatment and outcome of acute myocardial infarction: results from the Myocardial Infarction, Triage, and Intervention Registry. Arch Intern Med . 1992;;152:972-976.
Maynard C, Litwin PE, Martin JS, Weaver DW.  Treatment and outcome of acute myocardial infarction in women 75 years of age and older: findings from the Myocardial Infarction, Triage, and Intervention Registry. Cardiol Elderly . 1993;;1:121-125.
Tofler GH, Stone PH, Muller JE, Braunwald E.  Mortality for women after acute myocardial infarction: MILIS Study Group. Am J Cardiol . 1989;;64: 256.
Tofler GH, Stone PH, Muller JE, et al, for the MILIS Study Group.  Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women. J Am Coll Cardiol . 1987;;9:473-482.
Behar S, Zahavi Z, Goldbourt U, Reicher-Reiss H.  Long-term prognosis of patients with paroxysmal atrial fibrillation complicating acute myocardial infarction: SPRINT Study Group. Eur Heart J . 1992;;13:45-50.
Gomez-Marin O, Folsom AR, Kottke TE, et al.  Improvement in long-term survival among patients hospitalized with acute myocardial infarction: 1970 to 1980. N Engl J Med . 1987;;316:1353-1359.
Dittrich H, Gilpin E, Nicod P, Cali G, Henning H, Ross J Jr.  Acute myocardial infarction in women: influence of gender on mortality and prognostic variables. Am J Cardiol . 1988;;62:1-7.
Puletti M, Sunseri L, Curione M, Erba SM, Borgia C.  Acute myocardial infarction: sex-related differences in prognosis. Am Heart J . 1984;;108:63-66.
Fibrinolytic Therapy Trialists' (FTT) Collaborative Group.  Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet . 1994;;343:311-322.
White HD, Barbash GI, Modan M.  After correcting for worse baseline characteristics, women treated with thrombolytic therapy for acute myocardial infarction have the same mortality and morbidity as men except for a higher incidence of hemorrhagic stroke: the investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Study. Circulation . 1993;;88:2097-2103.
Fiebach NH, Viscoli CM, Horwitz RI.  Differences between women and men in survival after myocardial infarction: biology or methodology? JAMA . 1990;;263:1092-1096.
Greenland P, Reicher-Reiss H, Goldbourt U, Behar S, for the Israeli SPRINT Investigators.  In-hospital and 1-year mortality in 1,524 women after myocardial infarction: comparison with 4,315 men. Circulation . 1991;;83:484-491.
Lincoff AM, Califf RM, Ellis SG, et al, for the Thrombolysis and Angioplasty in Myocardial Infarction Study Group.  Thrombolytic therapy for women with myocardial infarction: is there a gender gap? J Am Coll Cardiol . 1993;;22:1780-1787.
Steingart RM, Packer M, Hamm P, et al, for the Survival and Ventricular Enlargement Investigators.  Sex differences in the management of coronary artery disease. N Engl J Med . 1991;;325:226-230.
Krumholz HM, Douglas PS, Lauer MS, Pasternak RC.  Selection of patients for coronary angiography and coronary revascularization early after myocardial infarction: is there evidence for gender bias? Ann Intern Med . 1991;;116:785-790.
Ayanian JZ, Epstein AM.  Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med . 1991;;325:221-225.
Mueller HS, Cohen LS, Braunwald E, et al, for the TIMI Investigators.  Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction: analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II. Circulation . 1992;;85: 1254-1264.
The GUSTO Investigators.  An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med . 1993;;329:673-682.
Lee KL, Woodlief LH, Topol EJ, et al, for the GUSTO-I Investigators.  Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41,021 patients. Circulation . 1995;;91:1659-1668.
The GUSTO Angiographic Investigators.  The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med . 1993;;329:1615-1622.
Weaver WD, Litwin PE, Martin JS, et al.  Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction: the MITI Project Group. J Am Coll Cardiol . 1991;;18:657-662.
Weaver WD, for the National Registry of Myocardial Infarction Investigators.  Factors influencing the time to hospital administration of thrombolytic therapy: results from a large national registry. Circulation . 1992;;86:1-16.
Ridolfo B, Jamrozik KD, Hobbs M, Parsons RW, Broadhurst RJ, Thompson PL.  Gender bias in management of myocardial infarction: prevalence and relevance to outcome. J Am Coll Cardiol . 1993;; 21:238A.
Maggioni AP, Franzosi MG, Santoro E, White H, Van de Werf F, Tognoni G, for the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico II (GISSI-2) and International Study Group.  The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. N Engl J Med . 1992;; 327:1-6.
Mazeika PK, Nadazdin A, Oakley CM.  Influence of haemodynamics and myocardial ischaemia on Doppler transmitral flow in patients undergoing dobutamine echocardiography. Eur Heart J . 1994;; 15:17-25.
Vasan RS, Benjamin EJ, Levy D.  Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol . 1995;;26:1565-1574.
Higginbotham MB, Morris KG, Coleman RE, Cobb FR.  Sex related differences in the normal cardiac response to upright exercise. Circulation . 1984;;70:357-366.
Chiriboga DE, Yarzebski J, Goldberg RJ, et al.  A community-wide perspective of gender differences and temporal trends in the use of diagnostic and revascularization procedures for acute myocardial infarction. Am J Cardiol . 1993;;71:268-273.
Maynard C, Weaver WD.  Treatment of women with acute MI: new findings from the MITI Registry. J Myocardial Ischemia . 1992;;4:27-37.

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Maynard C, Litwin PE, Martin JS, Weaver WD.  Gender differences in the treatment and outcome of acute myocardial infarction: results from the Myocardial Infarction, Triage, and Intervention Registry. Arch Intern Med . 1992;;152:972-976.
Maynard C, Litwin PE, Martin JS, Weaver DW.  Treatment and outcome of acute myocardial infarction in women 75 years of age and older: findings from the Myocardial Infarction, Triage, and Intervention Registry. Cardiol Elderly . 1993;;1:121-125.
Tofler GH, Stone PH, Muller JE, Braunwald E.  Mortality for women after acute myocardial infarction: MILIS Study Group. Am J Cardiol . 1989;;64: 256.
Tofler GH, Stone PH, Muller JE, et al, for the MILIS Study Group.  Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women. J Am Coll Cardiol . 1987;;9:473-482.
Behar S, Zahavi Z, Goldbourt U, Reicher-Reiss H.  Long-term prognosis of patients with paroxysmal atrial fibrillation complicating acute myocardial infarction: SPRINT Study Group. Eur Heart J . 1992;;13:45-50.
Gomez-Marin O, Folsom AR, Kottke TE, et al.  Improvement in long-term survival among patients hospitalized with acute myocardial infarction: 1970 to 1980. N Engl J Med . 1987;;316:1353-1359.
Dittrich H, Gilpin E, Nicod P, Cali G, Henning H, Ross J Jr.  Acute myocardial infarction in women: influence of gender on mortality and prognostic variables. Am J Cardiol . 1988;;62:1-7.
Puletti M, Sunseri L, Curione M, Erba SM, Borgia C.  Acute myocardial infarction: sex-related differences in prognosis. Am Heart J . 1984;;108:63-66.
Fibrinolytic Therapy Trialists' (FTT) Collaborative Group.  Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet . 1994;;343:311-322.
White HD, Barbash GI, Modan M.  After correcting for worse baseline characteristics, women treated with thrombolytic therapy for acute myocardial infarction have the same mortality and morbidity as men except for a higher incidence of hemorrhagic stroke: the investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Study. Circulation . 1993;;88:2097-2103.
Fiebach NH, Viscoli CM, Horwitz RI.  Differences between women and men in survival after myocardial infarction: biology or methodology? JAMA . 1990;;263:1092-1096.
Greenland P, Reicher-Reiss H, Goldbourt U, Behar S, for the Israeli SPRINT Investigators.  In-hospital and 1-year mortality in 1,524 women after myocardial infarction: comparison with 4,315 men. Circulation . 1991;;83:484-491.
Lincoff AM, Califf RM, Ellis SG, et al, for the Thrombolysis and Angioplasty in Myocardial Infarction Study Group.  Thrombolytic therapy for women with myocardial infarction: is there a gender gap? J Am Coll Cardiol . 1993;;22:1780-1787.
Steingart RM, Packer M, Hamm P, et al, for the Survival and Ventricular Enlargement Investigators.  Sex differences in the management of coronary artery disease. N Engl J Med . 1991;;325:226-230.
Krumholz HM, Douglas PS, Lauer MS, Pasternak RC.  Selection of patients for coronary angiography and coronary revascularization early after myocardial infarction: is there evidence for gender bias? Ann Intern Med . 1991;;116:785-790.
Ayanian JZ, Epstein AM.  Differences in the use of procedures between women and men hospitalized for coronary heart disease. N Engl J Med . 1991;;325:221-225.
Mueller HS, Cohen LS, Braunwald E, et al, for the TIMI Investigators.  Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction: analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II. Circulation . 1992;;85: 1254-1264.
The GUSTO Investigators.  An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med . 1993;;329:673-682.
Lee KL, Woodlief LH, Topol EJ, et al, for the GUSTO-I Investigators.  Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41,021 patients. Circulation . 1995;;91:1659-1668.
The GUSTO Angiographic Investigators.  The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med . 1993;;329:1615-1622.
Weaver WD, Litwin PE, Martin JS, et al.  Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction: the MITI Project Group. J Am Coll Cardiol . 1991;;18:657-662.
Weaver WD, for the National Registry of Myocardial Infarction Investigators.  Factors influencing the time to hospital administration of thrombolytic therapy: results from a large national registry. Circulation . 1992;;86:1-16.
Ridolfo B, Jamrozik KD, Hobbs M, Parsons RW, Broadhurst RJ, Thompson PL.  Gender bias in management of myocardial infarction: prevalence and relevance to outcome. J Am Coll Cardiol . 1993;; 21:238A.
Maggioni AP, Franzosi MG, Santoro E, White H, Van de Werf F, Tognoni G, for the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico II (GISSI-2) and International Study Group.  The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. N Engl J Med . 1992;; 327:1-6.
Mazeika PK, Nadazdin A, Oakley CM.  Influence of haemodynamics and myocardial ischaemia on Doppler transmitral flow in patients undergoing dobutamine echocardiography. Eur Heart J . 1994;; 15:17-25.
Vasan RS, Benjamin EJ, Levy D.  Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol . 1995;;26:1565-1574.
Higginbotham MB, Morris KG, Coleman RE, Cobb FR.  Sex related differences in the normal cardiac response to upright exercise. Circulation . 1984;;70:357-366.
Chiriboga DE, Yarzebski J, Goldberg RJ, et al.  A community-wide perspective of gender differences and temporal trends in the use of diagnostic and revascularization procedures for acute myocardial infarction. Am J Cardiol . 1993;;71:268-273.
Maynard C, Weaver WD.  Treatment of women with acute MI: new findings from the MITI Registry. J Myocardial Ischemia . 1992;;4:27-37.
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