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Prediction on Admission of In-Hospital Mortality in Patients Older Than 70 Years With Acute Myocardial Infarction
Prediction on Admission of In-Hospital Mortality in Patients Older Than 70 Years With Acute Myocardial Infarction* Gonzalo Suarez, MD; Manuel Herrera, MD; Antonio Vera, MD; Eliberto Torrado, MD; julio Fimiz, MD; and jose Andres Arboleda, MD
Study objective: To identify the differential characteristics regarding risk factors, presentation, and clinical status on hospital admission in patients aged 70 years or older with acute myocardial infarction (MI) of less than 24 h of evolution, compared with patients younger than 70 years, and to analyze possible factors that could affect mortality on admission in the group of patients older than 70 years. Study design: Of 1,289 patients admitted in the coronary care unit with acute MI during the period 1988 to 1991, with a delay from onset of symptoms of less than 24 h, we defined two groups according to age: younger than 70 years (group 1) and 70 years or older (group 2) in order to analyze the possible predictive factors for mortality on hospital admission in patients older than 70 years (n =322). By means of univariate analysis, we studied clinical variables that were present on admission; age; sex; medical history of diabetes, cerebrovascular accident, stable angina, previous MI, cardiac failure, right bundle branch block, and atrial fibrillation; previous treatment with digoxin, calcium antagonists, angiotensin-converting enzyme inhibitors (ACE!), antiaggregants or .B-blockers; location and extension of the acute MI, and thrombolysis. The association between mortality, as the dependent variable, and all other
variables, as independent variables, was evaluated using a stepwise logistical regression procedure. Results: In patients older than 70 years of age, the model included the following as independent predictors of mortality: female sex (odds ratio [OR], 2.59); complete right bundle branch block (CRBBB) (OR, 4.88); Q-wave MI (OR, 0.35 for non-Q-wave MI); and Forrester grade 2 to 3 (OR, 6.36) and 4 (OR, 80.14). Conclusions: In patients with acute MI and older than 70 years at the time of admission to the coronary care unit, together with the variables indicating the degree of hemodynamic involvement and the extension of the acute MI, factors such as female sex and CRBBB stand out as independent predictors of mortality. (CHEST 1995; 108:83-88)
coronary disease is the most frequent cause of death in people older than 65 years. The possibility of suffering an acute myocardial infarction (MI) in this population group is eight times higher than in people of a less advanced age.1 More than 50% of in-hospital mortality from acute MI occurs in subjects older than 65 years.2 It is therefore an important problem, likely to increase as the population becomes progressively older. 3 There is, however, some confusion as to what is an old person and what is a very old person. There are no clear limits, since these are usually defined arbitrarily depending more on socioeconomic or political circumstances than on the prevalence or severity of
the disease.4 In the older patient, a series of circumstances exists that may influence negatively the evolution of acute MI (worse baseline functional state, previous cardiac failure, cerebrovascular accident, diabetes mellitus, hypertension), making it more difficult to determine if the factors affecting mortality are the same as those described for younger patients. However, age has proved to be a determining factor in mortality in numerous studies, which has led to a restriction in the access of older patients to coronary care units (CCUs) and to doubts concerning the suitability of otherwise aggressive treatment despite the fact that the higher mortality rate in this population group could mean a greater number of lives saved per patient treated. We therefore undertook this study to determine the basic clinical characteristics of our older patients and to analyze which were independent predictors of
*From the Coronary Unit-Intensive Care Unit , Hospital Regional Carlos Haya, Malaga, Spain. Manuscript received March 23, 1994; revision accepted September I. Reprint requests: Dr. Suarez, Hospital " Carlos Haya ," Avda Carlos Haya , Malaga 29010 Spain
ACEI=angiotensin-converting enzyme inhibitors; AF= atrial fibrillation; AV=atrioventricular; CCU=coronary care unit; CLBBB=complete left bundle branch block; CRBBB=complete right bundle branch block; CVA= cerebrovascular accident; Ml=myocardial infarction; OR=odds ratio
Key words: acute myocardial infarction; age; mortality; risk factors
CHEST / 108 / 1 / JULY, 1995
83
mortality in patients older than 70 years with acute MI of less than 24 h of evolution on admission. MATERIALS AND METHODS We carried out a retrospective study of 1,289 consecutive patients admitted to the CCU between 1988 and 1991 with a diagnosis of acute Ml at hospital discharge and a delay of less than 24 h from onset of the symptoms. A diagnosis of acute MI was established by the presence of two of the three classic defining criteria: typical pain lasting longer than 30 min, determinant changes in the ECG, or enzymatic elevation with characteristic curve of creatine phosphokinase and lactate dehydrogenase. Data were taken from the clinical history, which is codified at the time of hospital discharge of each patient using a system designed by the unit and that remained unchanged during the study period , gathering uniformly in all patients the most important personal details, such as prior treatment, characteristics of the acute Ml, clinical course, and treatment administered. We defined two groups of patients according to age: younger than 70 years (group 1) and 70 years or older (group 2), obtaining details regarding age; sex; personal history (yes/no) of diabetes, cerebrovascular accident (CVA), stable angina, prior acute MI, cardiac failure, complete right bundle branch block (CRBBB), complete left bundle branch block (CLBBB), atrioventricular (A V) block, or atrial fibrillation (AF); previous treatment (yes/ no) with digoxin, calcium antagonists, ,8-blockers, angiotensin-converting enzyme inhibitors (ACEI) or antiaggregating medication; location of the acute MI (inferior, anterior, indeterminate, or combined); extension of the acute MI (acute Q-wave MI vs acute non-Q-wave MI) and administration (yes/no) of fibrinolytics on admission.
Statistical Analysis All grouped data are expressed as the mean± standard deviation (M ± SD), unless otherwise stated. The X2 test and Student's t test were used to detect possible differences between the two groups. For the variable "age," a logarithmic transformation was used to obtain a normal distribution. To analyze the possible predictive factors for mortality on admission in patients older than 70 years, the X2 or Student's t tests were used to select those variables with a significant association (p<0.05) with mortality. The association between mortality, as the dependent variable, and all other variables, as independent variables, was evaluated using a stepwise logistical regression procedure of computer software (SPSS/PC+ ). Forward stepwise procedures were used with a cutoff p value of 0.05 for inclusion of variables in the model, maintaining those variables with a Wald Statistic significance of less than 0.1. Categorization of the variable " location" was made using the location "inferior" as the indicator; in "extension" we used acute
Table !-Patient Profiles
No. of patients Sex, M/ F (% /% ) Age, yr (M / F)I Died (% ) *<70 years.
1>70 years.
IYears: mean±SD.
84
Group 1*
Group 21
967 835/ 132 (855/ 13.7) 56.28±8.76/ 60.08±7.87 95 (9.8)
322 225/97 (69.9/ 30.1) 74.41 ±4.09/ 76.09±4.34 86 (26.7)
Q-wave MI as the indicator; in the Forrester grade the indicator category was grade 1 and categories 2 and 3 were grouped together owing to the small number of patients in both groups. The variables fibrinolytic treatment and extension of the infarction have been included in the analysis, although they did not attain statistical significance, as they have been considered important in a broad number of previous studies. The prediction of mortality was made when a probability of death existed with a value (calculated according to the regression equation) greater than 0.5. We later calculated the sensitivity, specificity, and correct classification rate of this equation. RESULTS
Results of the Comparative Analysis Between the Two Studied Groups Patient Characteristics: The patients were distributed into two age groups: group 1, younger than 70 years (n =967) and group 2, those 70 years or older (n=322). See Table 1. Risk Factors: We analyzed the universally accepted risk factors and compared the prevalence in each age group (later relating these factors with mortality in group 2) . See Table 2. With respect to smoking, the proportion of smokers in group 2 decreased markedly (p<0.001). Diabetes and hypertension, however, were greater in this group. We found no differences between the groups when analyzing the prevalence of hypercholesterolemia. Ischemic Cardiac History: Almost 35% of all the patients studied (453 of 1,289 cases) had a history of ischemic cardiopathy (stable angina and / or previous
Table 2-History
Risk factors Smoking Diabetes Hypertension Hypercholesterolemia Cardiovascular Previous MI Stable angina CRBBB CLBBB AF Cardiac failure Digoxin CVA Medication* Antiaggregating ~-Blockers
Nitrates ACE! Ca-Antagonists
Group 1, No. (%) of Cases (n=967)
Group 2, No.( %) of Cases (n=322)
p Value
677 (70) 189 (19.5) 391 (40.1) 203 (21)
126 (391) 106 (32.9) 150 (46 6) 69 (21.4)
<0.0001 <0.0001 0.05 NS
203 (21) 179 (19.5) 4 (0.4) 7 (0.7) 18 (1.9) 21 (2.2) 37 (3.8) 44 (4.6)
65 (20.2) 78 (244) 11 (3.4) 4 (1.2) 13 (4) 16 (5) 28 (8.7) 25 (7.8)
NS <0.05 <0.0001 NS <0.05 <0.01 <0.001 <0.05
70 (21.4) 64 (19.6) 114 (34.9) 21 (6.4) 142 (43.4)
26 (21.5) 8 (6.6) 57 (47.1) 16 (13.2) 56 (46.3)
NS <0.001 <0.05 <0.05 NS
*n=453: Group 1=332; group 2=121. Clinical Investigations
group 1 vs 21.1 % in group 2 (p < 0.001) (Table 3) .
Table 3-Data on Admission
Admission delay* Thrombolysis Thrombolysis delay* Non-Q acute MI AV block Location Inferior Anterior Indeterminate Combined
Group 1, No.(%) of Cases
Group 2, No.(%) of Cases
p Value
6.29±0.17 433 (44.8) 4.17±0.18 276 (28.6) 26 (2.7)
7.98±0.31 68 (21.1) 4.38±0.33 98 (30.4) 15 (4.7)
<0.001 <0.001 NS NS NS
470 (48.6) 409 (423) 57 (5.89) 31 (32)
135 (41.9) 155 (48.1) 14 (4.35) 18 (5.59)
*Hours: mean±SEM.
acute MI) . There were no statistical differences in previous acute MI in either group, although almost 25% of the patients in group 2 had a positive history of stable angina vs 19.5% in group 1. The prevalence of CRBBB, AF, and previous cardiac failure was significantly greater in group 2. Digoxin was prescribed more frequently in this group (p < 0.001). See Table 2. Previous Cardiovascular Medication: To analyze the possible significance of generally prescribed drugs, we selected a subgroup of patients based on the presence of prior ischemic cardiac disease (n=453) (Table 2). Antiaggregating medication presented no significant differences in either group, although the scant use of these therapeutic agents was noticeable (<22% in each group). Oral f)-blockers were used scarcely as well, despite their indication as a secondary preventive measure, their use being restricted to patients in group 1 (p< 0.001) . Nitrates were used in almost 50% of patients in group 2. Calcium antagonists were used in both groups (45% of the cases), possibly for their indication as antihypertensive agents. Analysis of Delay on Admission: There was a significant difference in the time between onset of the symptoms and admission to the CCU between the groups, being more prolonged in group 2 (Table 3). Location and Extension of the Infarction: There was a greater incidence of anterior acute MI (48.1%) in the patients in group 2, whereas in group 1 there was a predominance of inferoposterior location (48.6%) (Table 3). There were no significant differences in the extension of the acute MI. Forrester Data on Admission: Group 2 had a higher degree of hemodynamic involvement, with a lower number of patients admitted in Forrester 1 compared with the younger patients (Fig 1). Use of Thrombolytic Drugs on Admission: The use of thrombolytic drugs was significantly different, having been administered in 44.8% of patients in
Results of the Analysis of Mortality in Patients Older Than 70 Years Univariate analysis of in-hospital mortality in group 2 showed the following: the percentage of deaths related to the presence or absence of a history of risk factors is shown in Tables 4 and 5. There was no significant relation between mortality and any of the following: diabetes, hypercholesterolemia , smoking, hypertension, prior ischemic cardiopathy (acute MI or stable angina), previous cardiac failure, previous CVA, previous AF, previous treatment with calcium antagonists, f)-blockers, nitrates, ACEI, or digoxin, or with the location or extension of the present acute MI, or use of fibrinolytic treatment. On the other hand, sex, Forrester grade on admission (Fig 2) , CRBBB, and complete AV block (Table 5) on admission did show a significant relation. Those patients who died were older than those who survived (75.8 vs 74.6 years: p < 0.05). The only independent predictors of mortality included in the logistical regression model were sex (odds ratio [OR], 2.59 for women vs men), CRBBB (OR, 4.88), acute Q-wave MI (OR, 0.35 for acute non-Q-wave MI), and Forrester grades: 2 to 3 (OR, 6.36), 4 (OR, 80.14) (Table 6) . Age was excluded by the model. The model had a specificity of 98.18 % and a sensitivity of 28.4%, with a correct classification rate of 79.4%.
13,6 25,5
3 5 ,6
Forrester FIGURE L Distribution of patients according to Forrester class. CHEST / 108 / 1 / JULY, 1995
85
Table 4-Relation of the Studied Variables to Mortality in Patients Older Than 70 Years* Variable
Yest
Not
p Value
F emale sex History Diabetes Smoking H ypercholeste rolemia Hypertension Cardiovascular Stable angina Prior acute MI Cardiac failure
32.99 (97 )
24 (225 )
0.05
AF
CVA Medication Digoxin Antiarrh ythmics
(216) (196) (253) (172)
28.3 (106) 22.2 (126) 24.6 (69) 28 (150)
25.9 29.6 27.3 25.6
33.3 (78) 24.6 (65) 43.7 (16) 38.6 (13) 32 (25 )
24.6 (244) 27.2 (257 ) 25. 8 (306) 26.2 (309) 26.3 (297 )
32.1 (28) 25 ( 16)
26.2 (294) 26.8 (306)
Mo rtality (%)
100
NS
s
NS NS
NS
s
NS
s
NS
s s
*Pe rcentage o f d ae ths in pa tients who present or do not present the studied variables on admission. t% deaths ( or . of pa tients). DISCUSSION
We designed the present study in order to create an outline model of older patients who, on admission, have predictive factors of a worse evolution and a higher risk of in-hospital death and which, owing to the paucity of information available for this patient group, would facilitate decision making. Coronary disease is the most frequent cause of death in persons older than 65 years. Over half of all patients hospitalized for acute MI are over this age. 2 •5 •6 Although the percentage of our older patients was lower, we used a higher limit (70 years) and took into account only those admissions to the CCU with less than 24 h of evolution, so that a considerable number of patients were not included (the global percentage of acute MI is likely to be higher) . The main problem concerning these patients is to state a limit above which they are to be considered old, and to define the differential characteristics in this group. Age limits of 65, 70, or 75 years have all Table 5-Relation of Mortality and Clinical Data on Admission in Group 2* Variable
Yest
Not
p Value
Thrombolysis CRBBB CLBBB AV block Non-Q acute MI Location Inferior acute MI Anterior acute MI Combined acute MI Indetermina te acute MI
20.6 (68) 63.6 (11) 25 (4) 53.3 (15) 21.4 (98)
28.4 (254) 25.4 (311 ) 26.7 (318) 25.4 (307) 29 (224)
NS <0.001 NS <0.05 NS
21.5 (135) 27.7 (155) 38.9 (18) 50 (14)
FIGURE 2. Relation of mortality with Forreste r class in group 2.
been considered, as well as division of the patients into two groups, old and very old. We found that age was no longer a predictive factor of death in the group of patients older than 70 years, so we believe it is not necessary to differentiate the old from the very old. Older patients have an increased prevalence of poor prognostic factors, including a history of angina pectoris (24.4 %), previous cardiac failure (5%), previous acute MI (20.2%), systemic hypertension (46.6%), diabetes mellitus (32.9%), and female sex (30.1 %). 7 Postinfarction angor and reinfarction have a twofold incidence in older people. 8-10 Except for prior acute Ml, we found a significant increase in all these factors with respect to younger patients. It should also be noted that older patients come to the hospital later and have greater hemodynamic involvement on admission (partly explaining the higher incidence of AF or CRBBB). Age is the most important clinical variable in the Table 6-Logistic Regression Model
s NS NS NS
*Percentage of deaths in patients who present or do not present the studied variables on admission. t% deaths ( o.of patients).
86
Forrester
Sex CRBBB Non-Q acute MI F arrester 2-3 Forrester 4
Wald*
p Value
R
OR
8.6502 4.3258 8.3855 34.0785 15.7758
0.0033 0.0375 0.0038 0.0000 0.0001
0.1377 0.0814 -0.135 0.3025 0.1982
2.59 4.88 0.35 6.36 80.14
*Wald sta tistic. Clinical Investigations
prediction of the evolution of acute MI. In-hospital mortality from acute MI rises significantly as the age of the patients increases, being 2.5% in young patients, 5to 9% in middle-aged patients, and 21 % in older patients (older than 75 years), 11 -13 a similar figure to ours. Other poor prognostic factors historically related with an increase in mortality are female sex, cardiac failure , CV A, Forrester class, diabetes mellitus, high diastolic blood pressure, AF, use of digitalis, and prior acute MI.l 4- 23 Paradoxically , in our group of patients older than 70 years, only the subjects' sex, presence of AV block, degree of hemodynamic involvement on admission, and the existence of CRBBB had a statistically significant relation , although we evaluated only in-hospital mortality and not medium- or long-term mortality, so that these data are not therefore conclusive. When evaluating the previous studies published in which logistical regression analyses have been applied, only age and cardiac failure indexes appear as independent determiners of mortality in all of them. Previous acute MI, extension of the infarction , and the existence of nonpainful acute MI (not evaluated in our study) have been shown less uniformly to be independent predictors of mortality. Nevertheless, according to our results , any age over 70 years is not a determinant of mortality . The existence of CRBBB on admission 24 proved to be predictive of mortality in our model, a fact that has previously been reported by other authors who have interpreted this as an expression of greater extension of the acute MI. 25 Our model has a sensitivity of only 28.4%, but we excluded those parameters appearing during hospitalization , which might have influenced mortality (with their inclusion it is logical to suppose that the sensitivity would have improved), since on designing the study we fixed as an objective the ability to make a prediction of mortality at the time of admission. Although the prognosis after acute MI has changed significantly since the introduction of thrombolytic drugs, this treatment has been systematically denied to patients older than 75 years (despite the fact that mortality among these is higher) because of the presentation of a greater number of complications. 26-31 According to the results obtained in recently published international multicentric studies, analyzing the behavior of different population groups in relation to this treatment, the use of an age limit as a restrictive criterion for the use of thrombolytic therapy cannot now be considered appropriate. In our group, the percentage of patients receiving this treatment is high (21.1%), despite which we have been unable to detect a significant favorable influence of this fact on mortality , which we believe to be due to the limited size of the sample.32- 44 Our data , therefore, agree with previous reports
regarding the consideration of the hemodynamic situation on admission, a greater extension of the acute MI, or female sex as factors predicting mortality . We believe that these results will enable us to delimit those patients who will obtain greater benefit from their admission to the CCU, as well as the use of thrombolytic or other aggressive therapy, both always difficult decisions in this age group. CONCLUSIONS
In patients older than 70 years of age, together with the degree of hemodynamic involvement and extension of the acute MI, sex and right bundle branch block are independent predictors of mortality on admission to the hospital. Age is no longer a predictive factor of mortality in these patients, so we do not believe the differentiation into old and very old patients is necessary. REFERENCES
1 De Fockert JA. De klinische presentatie van het acute myocardinfarct op hogere leeftijd. Tijdschr Gerontal Geriatr 1987; 18:305-08 2 Wenger NK, Fur berg CD, Pitt E. Coronary heart disease in the elderly: review of current knowledge and research recommendations. In: Wenger NK, Furberg CD, Pitt E, eds. Coronary heart disease in the elderly. New York: Elsevier, 1986; 1-7 3 Friedewald WT. Cardiovascular disease in the elderly. J Am Coli Cardiol1 987; 10(suppl A):7 A-BA 4 Adolph RJ. The elderly, the very elderly and traditional practice patterns. J Am Coli Cardiol 1990; 16:793-94 5 Sato H, Tateishi H, Uchida T, et al. Acute myocardial infarction in the elderly. Jpn Circ J 1988; 52:454-59 6 House MA. Thrombolytic therapy for acute myocardial infarction: the elderly population. AACN Clin Issues Crit Care Nurs 1992; 3:106-13 7 Ferriz J A,Vera A, Suarez G, et al. Sexo femenino y mortalidad tras infarto agudo de miocardia. Rev Esp Cardiol 1994; 46: 796-82 8 Tofler GH, Muller JE, Stone PH, eta!. Factors leading to shorter survival after acute myocardial infarction in patients aged 65 to 75 years com pared with younger patien ts. Am J Cardiol1988; 62:860-67 9 Weaver WD, Litwin PE, Martin JS, eta!. Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction: the MITI project group. J Am Coli Cardiol 1991 ; 18:657-62 10 Martinez Sande JL, Amaro Cendon A, Gonzalez Juanatey JR, et al. Implicaciones clinicas y pron6sticas de Ia edad en el infarto agudo de miocardio. Arch Inst Cardiol Mex 1991; 61:579-86 11 Hoit BD, Gilpin EA, Henning H , et al. Myocardial infarction in young patients: an analysis by age subsets. Circulation 1986; 74:712-21 12 Montague TJ, Ikuta RM, Wong RY, et a!. Comparison of risk and patterns of practice in patients older and younger than 70 years with acute myocardial infarction in a 2-year period (1987-1989). Am J Cardiol1991; 68:843-47 13 Garcia Rubira JC, Romero D, Garcia Martinez JT, eta!. Infarto agudo de miocardio en octogenarios. Med Intensiva 1991; 15:86-8 14 Olmsted WL, Groden DL, Silverman ME. Prognosis in surviCHEST / 108 / 1 / JULY, 1995
87
vors of acute myocardial infarction occurring at age 70 years or older. Am J Cardiol1987; 60:971-75 15 Castello R, Alegria E, Olmos L, et al. El infarto agudo de miocardia en pacientes mayores de 65 aiios. Rev Med Univ Navarra 1987; 31:81-4 16 Day JJ, Bayer AJ, Pathy MS, et al. Acute myocardial infarction: diagnostic difficulties and outcome in advanced old age. Age Ageing 1987; 16:239-43 17 Castello R, Alegria E, Merino A, et al. Effect of age on long-term prognosis of patients with myocardial infarction. Int J Cardiol 1988; 20:221-30 18 Yang XS, Willems JL, Pardaens J, et al. Acute myocardial infarction in the very elderly: a comparison with younger age groups. Acta Cardiol1987; 42:59-68 19 Schafer JH, Maurer A, Arntz HR, et al. Akuter Myokardinfarkt: Aspekte der veranderten Sterblichkeit auf der Intensivstation: Ergebnisse einer prospektiven Untersuchung der Jahre 1985 bis 1987. Dtsch Med Wochenschr 1989; 114:1143-48 20 Petretta M, Canonico V, Bianchi V, et al. Influenza dell'eta sulla prognosi a breve e medio termine nei pazienti con infarto acuto del miocardio. G Ita! Cardiol1991; 21:395-408 21 Chua TS, Koo CC, Tan AT, et al. Mortality trends in the coronary care unit. Ann Acad Med Singapore 1990; 19:3-8 22 Day JJ, Bayer AJ, ChadhaJS, et al. Myocardial infarction in old people: the influence of diabetes mellitus. J Am Geriatr Soc 1988; 36:791-94 23 Chaitman BR, Thompson B, Wittry MD, et al. The use of tissue-type plasminogen activator for acute myocardial infarction in the elderly: results from thrombolysis in myocardial infarction phase I, open label studies and the thrombolysis in myocardial infarction phase II pilot study: The TIM! investigators. J Am Coli Cardiol 1989; 14:1159-65 24 Wellens HJJ. Right ventricular infarction. N Engl J Med 1993; 328:1036-38 25 Martinez Sande JL, Casariego R, Alonso 0, et al. El infarto de miocardio en el paciente geriatrico: factores pron6sticos a corto y medio plazo. Rev Esp Cardiol1992; 45:365-73 26 Vogel JH, Setty RK, Coughlin BJ, et al. Intravenous streptokinase in acute myocardial infarction at the community hospital: a 6-year experience. Am J Cardiol 1988; 62:25K-27K 27 Pedro PC, Pereirinha A, Fiuza M, et al. Trombolise no enfarte agudo de miocardio no idoso: urn risco acrescido de ruptura cardiaca? Rev Port Cardiol1991; 10:133-39 28 White H, Cross D, Scott M, et al. Comparison of effects of thrombolytic therapy on left ventricular function in patients over with those under 60 years of age. Am J Cardiol1991; 67: 913-18 29 Pendlebury WW, Iole ED, Tracy RP, et al. Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Ann Neurol1991; 29:210-13 30 Fleming C, D'Agostino RB, Selker HP. Is coronary-care-unit admission restricted for elderly patients? a multicenter study.
88
Am J Public Health 1991; 81:1121-26 31 Cragg DR, Friedman HZ, Bonema JD, et al. Outcome of patients with acute myocardial infarction who are ineligible for thrombolytic therapy. Ann Intern Med 1991; 115:173-77 32 Maggioni AP, Franzosi MG, Santoro E, et al. The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio II (GISSI-2) and the International Study Group. N Engl J Med 1992; 327:1-6 33 ISIS-3 (Third International Study of Infarct Survival) Collaborative group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41 ,299 cases of suspected acute myocardial infarction. Lancet 1992; 339:753-70 34 Krumholz HM, Pasternak RC, Weinstein MC, et al. Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. N Engl J Med 1992; 327:7-13 35 Johnston FA, Dunn FG, Hogg KJ, et al. Thrombolytic therapy in acute myocardial infarction in the elderly. Gerontology 1987; 33:331-39 36 Goldberg RJ, Gore JM, Gurwitz JH, et al. The impact of age on the incidence and prognosis of initial acute myocardial infarction: the Worcester Heart Attack Study. Am Heart J 1989; 17:543-49 37 Muller DW, Topol EJ. Selection of patients with acute myocardial infarction for thrombolytic therapy. Ann Intern Med 1990; 113:949-60 38 Feldman RL, Kaizer J, Standley M. Initial treatment of patients with acute ischemic heart disease hospitalized in a community hospital. Am J Cardiol1991 ; 68:61C-66C 39 Kline EM. Clinical controversies surrounding thrombolytic therapy in acute myocardial infarction. Heart Lung 1990; 19:596-601 40 Grines CL, de Maria AN. Optimal utilization of thrombolytic therapy for acute myocardial infarction. J Am Coli Cardiol 1990; 16:223-31 41 AIMS trial study group. Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. Lancet 1988; 1:545-49 42 ISIS-2 Collaborative group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2:349-61 43 Hendra TJ, Marshall AJ. Increased prescription of thrombolytic treatment to elderly patients with suspected acute myocardial infarction associated with audit. BMJ 1992; 304:423-25 44 Althouse R, Maynard C, Cerqueira M, et al. The western Washington Myocardial Infarction Registry and Emergency Department Tissue Plasminogen Activator Treatment Trial. Am J Cardiol1990; 66:1298-1303
Clinical Investigations
Study objective: To identify the differential characteristics regarding risk factors, presentation, and clinical status on hospital admission in patients aged 70 years or older with acute myocardial infarction (MI) of less than 24 h of evolution, compared with patients younger than 70 years, and to analyze possible factors that could affect mortality on admission in the group of patients older than 70 years. Study design: Of 1,289 patients admitted in the coronary care unit with acute MI during the period 1988 to 1991, with a delay from onset of symptoms of less than 24 h, we defined two groups according to age: younger than 70 years (group 1) and 70 years or older (group 2) in order to analyze the possible predictive factors for mortality on hospital admission in patients older than 70 years (n =322). By means of univariate analysis, we studied clinical variables that were present on admission; age; sex; medical history of diabetes, cerebrovascular accident, stable angina, previous MI, cardiac failure, right bundle branch block, and atrial fibrillation; previous treatment with digoxin, calcium antagonists, angiotensin-converting enzyme inhibitors (ACE!), antiaggregants or .B-blockers; location and extension of the acute MI, and thrombolysis. The association between mortality, as the dependent variable, and all other
variables, as independent variables, was evaluated using a stepwise logistical regression procedure. Results: In patients older than 70 years of age, the model included the following as independent predictors of mortality: female sex (odds ratio [OR], 2.59); complete right bundle branch block (CRBBB) (OR, 4.88); Q-wave MI (OR, 0.35 for non-Q-wave MI); and Forrester grade 2 to 3 (OR, 6.36) and 4 (OR, 80.14). Conclusions: In patients with acute MI and older than 70 years at the time of admission to the coronary care unit, together with the variables indicating the degree of hemodynamic involvement and the extension of the acute MI, factors such as female sex and CRBBB stand out as independent predictors of mortality. (CHEST 1995; 108:83-88)
coronary disease is the most frequent cause of death in people older than 65 years. The possibility of suffering an acute myocardial infarction (MI) in this population group is eight times higher than in people of a less advanced age.1 More than 50% of in-hospital mortality from acute MI occurs in subjects older than 65 years.2 It is therefore an important problem, likely to increase as the population becomes progressively older. 3 There is, however, some confusion as to what is an old person and what is a very old person. There are no clear limits, since these are usually defined arbitrarily depending more on socioeconomic or political circumstances than on the prevalence or severity of
the disease.4 In the older patient, a series of circumstances exists that may influence negatively the evolution of acute MI (worse baseline functional state, previous cardiac failure, cerebrovascular accident, diabetes mellitus, hypertension), making it more difficult to determine if the factors affecting mortality are the same as those described for younger patients. However, age has proved to be a determining factor in mortality in numerous studies, which has led to a restriction in the access of older patients to coronary care units (CCUs) and to doubts concerning the suitability of otherwise aggressive treatment despite the fact that the higher mortality rate in this population group could mean a greater number of lives saved per patient treated. We therefore undertook this study to determine the basic clinical characteristics of our older patients and to analyze which were independent predictors of
*From the Coronary Unit-Intensive Care Unit , Hospital Regional Carlos Haya, Malaga, Spain. Manuscript received March 23, 1994; revision accepted September I. Reprint requests: Dr. Suarez, Hospital " Carlos Haya ," Avda Carlos Haya , Malaga 29010 Spain
ACEI=angiotensin-converting enzyme inhibitors; AF= atrial fibrillation; AV=atrioventricular; CCU=coronary care unit; CLBBB=complete left bundle branch block; CRBBB=complete right bundle branch block; CVA= cerebrovascular accident; Ml=myocardial infarction; OR=odds ratio
Key words: acute myocardial infarction; age; mortality; risk factors
CHEST / 108 / 1 / JULY, 1995
83
mortality in patients older than 70 years with acute MI of less than 24 h of evolution on admission. MATERIALS AND METHODS We carried out a retrospective study of 1,289 consecutive patients admitted to the CCU between 1988 and 1991 with a diagnosis of acute Ml at hospital discharge and a delay of less than 24 h from onset of the symptoms. A diagnosis of acute MI was established by the presence of two of the three classic defining criteria: typical pain lasting longer than 30 min, determinant changes in the ECG, or enzymatic elevation with characteristic curve of creatine phosphokinase and lactate dehydrogenase. Data were taken from the clinical history, which is codified at the time of hospital discharge of each patient using a system designed by the unit and that remained unchanged during the study period , gathering uniformly in all patients the most important personal details, such as prior treatment, characteristics of the acute Ml, clinical course, and treatment administered. We defined two groups of patients according to age: younger than 70 years (group 1) and 70 years or older (group 2), obtaining details regarding age; sex; personal history (yes/no) of diabetes, cerebrovascular accident (CVA), stable angina, prior acute MI, cardiac failure, complete right bundle branch block (CRBBB), complete left bundle branch block (CLBBB), atrioventricular (A V) block, or atrial fibrillation (AF); previous treatment (yes/ no) with digoxin, calcium antagonists, ,8-blockers, angiotensin-converting enzyme inhibitors (ACEI) or antiaggregating medication; location of the acute MI (inferior, anterior, indeterminate, or combined); extension of the acute MI (acute Q-wave MI vs acute non-Q-wave MI) and administration (yes/no) of fibrinolytics on admission.
Statistical Analysis All grouped data are expressed as the mean± standard deviation (M ± SD), unless otherwise stated. The X2 test and Student's t test were used to detect possible differences between the two groups. For the variable "age," a logarithmic transformation was used to obtain a normal distribution. To analyze the possible predictive factors for mortality on admission in patients older than 70 years, the X2 or Student's t tests were used to select those variables with a significant association (p<0.05) with mortality. The association between mortality, as the dependent variable, and all other variables, as independent variables, was evaluated using a stepwise logistical regression procedure of computer software (SPSS/PC+ ). Forward stepwise procedures were used with a cutoff p value of 0.05 for inclusion of variables in the model, maintaining those variables with a Wald Statistic significance of less than 0.1. Categorization of the variable " location" was made using the location "inferior" as the indicator; in "extension" we used acute
Table !-Patient Profiles
No. of patients Sex, M/ F (% /% ) Age, yr (M / F)I Died (% ) *<70 years.
1>70 years.
IYears: mean±SD.
84
Group 1*
Group 21
967 835/ 132 (855/ 13.7) 56.28±8.76/ 60.08±7.87 95 (9.8)
322 225/97 (69.9/ 30.1) 74.41 ±4.09/ 76.09±4.34 86 (26.7)
Q-wave MI as the indicator; in the Forrester grade the indicator category was grade 1 and categories 2 and 3 were grouped together owing to the small number of patients in both groups. The variables fibrinolytic treatment and extension of the infarction have been included in the analysis, although they did not attain statistical significance, as they have been considered important in a broad number of previous studies. The prediction of mortality was made when a probability of death existed with a value (calculated according to the regression equation) greater than 0.5. We later calculated the sensitivity, specificity, and correct classification rate of this equation. RESULTS
Results of the Comparative Analysis Between the Two Studied Groups Patient Characteristics: The patients were distributed into two age groups: group 1, younger than 70 years (n =967) and group 2, those 70 years or older (n=322). See Table 1. Risk Factors: We analyzed the universally accepted risk factors and compared the prevalence in each age group (later relating these factors with mortality in group 2) . See Table 2. With respect to smoking, the proportion of smokers in group 2 decreased markedly (p<0.001). Diabetes and hypertension, however, were greater in this group. We found no differences between the groups when analyzing the prevalence of hypercholesterolemia. Ischemic Cardiac History: Almost 35% of all the patients studied (453 of 1,289 cases) had a history of ischemic cardiopathy (stable angina and / or previous
Table 2-History
Risk factors Smoking Diabetes Hypertension Hypercholesterolemia Cardiovascular Previous MI Stable angina CRBBB CLBBB AF Cardiac failure Digoxin CVA Medication* Antiaggregating ~-Blockers
Nitrates ACE! Ca-Antagonists
Group 1, No. (%) of Cases (n=967)
Group 2, No.( %) of Cases (n=322)
p Value
677 (70) 189 (19.5) 391 (40.1) 203 (21)
126 (391) 106 (32.9) 150 (46 6) 69 (21.4)
<0.0001 <0.0001 0.05 NS
203 (21) 179 (19.5) 4 (0.4) 7 (0.7) 18 (1.9) 21 (2.2) 37 (3.8) 44 (4.6)
65 (20.2) 78 (244) 11 (3.4) 4 (1.2) 13 (4) 16 (5) 28 (8.7) 25 (7.8)
NS <0.05 <0.0001 NS <0.05 <0.01 <0.001 <0.05
70 (21.4) 64 (19.6) 114 (34.9) 21 (6.4) 142 (43.4)
26 (21.5) 8 (6.6) 57 (47.1) 16 (13.2) 56 (46.3)
NS <0.001 <0.05 <0.05 NS
*n=453: Group 1=332; group 2=121. Clinical Investigations
group 1 vs 21.1 % in group 2 (p < 0.001) (Table 3) .
Table 3-Data on Admission
Admission delay* Thrombolysis Thrombolysis delay* Non-Q acute MI AV block Location Inferior Anterior Indeterminate Combined
Group 1, No.(%) of Cases
Group 2, No.(%) of Cases
p Value
6.29±0.17 433 (44.8) 4.17±0.18 276 (28.6) 26 (2.7)
7.98±0.31 68 (21.1) 4.38±0.33 98 (30.4) 15 (4.7)
<0.001 <0.001 NS NS NS
470 (48.6) 409 (423) 57 (5.89) 31 (32)
135 (41.9) 155 (48.1) 14 (4.35) 18 (5.59)
*Hours: mean±SEM.
acute MI) . There were no statistical differences in previous acute MI in either group, although almost 25% of the patients in group 2 had a positive history of stable angina vs 19.5% in group 1. The prevalence of CRBBB, AF, and previous cardiac failure was significantly greater in group 2. Digoxin was prescribed more frequently in this group (p < 0.001). See Table 2. Previous Cardiovascular Medication: To analyze the possible significance of generally prescribed drugs, we selected a subgroup of patients based on the presence of prior ischemic cardiac disease (n=453) (Table 2). Antiaggregating medication presented no significant differences in either group, although the scant use of these therapeutic agents was noticeable (<22% in each group). Oral f)-blockers were used scarcely as well, despite their indication as a secondary preventive measure, their use being restricted to patients in group 1 (p< 0.001) . Nitrates were used in almost 50% of patients in group 2. Calcium antagonists were used in both groups (45% of the cases), possibly for their indication as antihypertensive agents. Analysis of Delay on Admission: There was a significant difference in the time between onset of the symptoms and admission to the CCU between the groups, being more prolonged in group 2 (Table 3). Location and Extension of the Infarction: There was a greater incidence of anterior acute MI (48.1%) in the patients in group 2, whereas in group 1 there was a predominance of inferoposterior location (48.6%) (Table 3). There were no significant differences in the extension of the acute MI. Forrester Data on Admission: Group 2 had a higher degree of hemodynamic involvement, with a lower number of patients admitted in Forrester 1 compared with the younger patients (Fig 1). Use of Thrombolytic Drugs on Admission: The use of thrombolytic drugs was significantly different, having been administered in 44.8% of patients in
Results of the Analysis of Mortality in Patients Older Than 70 Years Univariate analysis of in-hospital mortality in group 2 showed the following: the percentage of deaths related to the presence or absence of a history of risk factors is shown in Tables 4 and 5. There was no significant relation between mortality and any of the following: diabetes, hypercholesterolemia , smoking, hypertension, prior ischemic cardiopathy (acute MI or stable angina), previous cardiac failure, previous CVA, previous AF, previous treatment with calcium antagonists, f)-blockers, nitrates, ACEI, or digoxin, or with the location or extension of the present acute MI, or use of fibrinolytic treatment. On the other hand, sex, Forrester grade on admission (Fig 2) , CRBBB, and complete AV block (Table 5) on admission did show a significant relation. Those patients who died were older than those who survived (75.8 vs 74.6 years: p < 0.05). The only independent predictors of mortality included in the logistical regression model were sex (odds ratio [OR], 2.59 for women vs men), CRBBB (OR, 4.88), acute Q-wave MI (OR, 0.35 for acute non-Q-wave MI), and Forrester grades: 2 to 3 (OR, 6.36), 4 (OR, 80.14) (Table 6) . Age was excluded by the model. The model had a specificity of 98.18 % and a sensitivity of 28.4%, with a correct classification rate of 79.4%.
13,6 25,5
3 5 ,6
Forrester FIGURE L Distribution of patients according to Forrester class. CHEST / 108 / 1 / JULY, 1995
85
Table 4-Relation of the Studied Variables to Mortality in Patients Older Than 70 Years* Variable
Yest
Not
p Value
F emale sex History Diabetes Smoking H ypercholeste rolemia Hypertension Cardiovascular Stable angina Prior acute MI Cardiac failure
32.99 (97 )
24 (225 )
0.05
AF
CVA Medication Digoxin Antiarrh ythmics
(216) (196) (253) (172)
28.3 (106) 22.2 (126) 24.6 (69) 28 (150)
25.9 29.6 27.3 25.6
33.3 (78) 24.6 (65) 43.7 (16) 38.6 (13) 32 (25 )
24.6 (244) 27.2 (257 ) 25. 8 (306) 26.2 (309) 26.3 (297 )
32.1 (28) 25 ( 16)
26.2 (294) 26.8 (306)
Mo rtality (%)
100
NS
s
NS NS
NS
s
NS
s
NS
s s
*Pe rcentage o f d ae ths in pa tients who present or do not present the studied variables on admission. t% deaths ( or . of pa tients). DISCUSSION
We designed the present study in order to create an outline model of older patients who, on admission, have predictive factors of a worse evolution and a higher risk of in-hospital death and which, owing to the paucity of information available for this patient group, would facilitate decision making. Coronary disease is the most frequent cause of death in persons older than 65 years. Over half of all patients hospitalized for acute MI are over this age. 2 •5 •6 Although the percentage of our older patients was lower, we used a higher limit (70 years) and took into account only those admissions to the CCU with less than 24 h of evolution, so that a considerable number of patients were not included (the global percentage of acute MI is likely to be higher) . The main problem concerning these patients is to state a limit above which they are to be considered old, and to define the differential characteristics in this group. Age limits of 65, 70, or 75 years have all Table 5-Relation of Mortality and Clinical Data on Admission in Group 2* Variable
Yest
Not
p Value
Thrombolysis CRBBB CLBBB AV block Non-Q acute MI Location Inferior acute MI Anterior acute MI Combined acute MI Indetermina te acute MI
20.6 (68) 63.6 (11) 25 (4) 53.3 (15) 21.4 (98)
28.4 (254) 25.4 (311 ) 26.7 (318) 25.4 (307) 29 (224)
NS <0.001 NS <0.05 NS
21.5 (135) 27.7 (155) 38.9 (18) 50 (14)
FIGURE 2. Relation of mortality with Forreste r class in group 2.
been considered, as well as division of the patients into two groups, old and very old. We found that age was no longer a predictive factor of death in the group of patients older than 70 years, so we believe it is not necessary to differentiate the old from the very old. Older patients have an increased prevalence of poor prognostic factors, including a history of angina pectoris (24.4 %), previous cardiac failure (5%), previous acute MI (20.2%), systemic hypertension (46.6%), diabetes mellitus (32.9%), and female sex (30.1 %). 7 Postinfarction angor and reinfarction have a twofold incidence in older people. 8-10 Except for prior acute Ml, we found a significant increase in all these factors with respect to younger patients. It should also be noted that older patients come to the hospital later and have greater hemodynamic involvement on admission (partly explaining the higher incidence of AF or CRBBB). Age is the most important clinical variable in the Table 6-Logistic Regression Model
s NS NS NS
*Percentage of deaths in patients who present or do not present the studied variables on admission. t% deaths ( o.of patients).
86
Forrester
Sex CRBBB Non-Q acute MI F arrester 2-3 Forrester 4
Wald*
p Value
R
OR
8.6502 4.3258 8.3855 34.0785 15.7758
0.0033 0.0375 0.0038 0.0000 0.0001
0.1377 0.0814 -0.135 0.3025 0.1982
2.59 4.88 0.35 6.36 80.14
*Wald sta tistic. Clinical Investigations
prediction of the evolution of acute MI. In-hospital mortality from acute MI rises significantly as the age of the patients increases, being 2.5% in young patients, 5to 9% in middle-aged patients, and 21 % in older patients (older than 75 years), 11 -13 a similar figure to ours. Other poor prognostic factors historically related with an increase in mortality are female sex, cardiac failure , CV A, Forrester class, diabetes mellitus, high diastolic blood pressure, AF, use of digitalis, and prior acute MI.l 4- 23 Paradoxically , in our group of patients older than 70 years, only the subjects' sex, presence of AV block, degree of hemodynamic involvement on admission, and the existence of CRBBB had a statistically significant relation , although we evaluated only in-hospital mortality and not medium- or long-term mortality, so that these data are not therefore conclusive. When evaluating the previous studies published in which logistical regression analyses have been applied, only age and cardiac failure indexes appear as independent determiners of mortality in all of them. Previous acute MI, extension of the infarction , and the existence of nonpainful acute MI (not evaluated in our study) have been shown less uniformly to be independent predictors of mortality. Nevertheless, according to our results , any age over 70 years is not a determinant of mortality . The existence of CRBBB on admission 24 proved to be predictive of mortality in our model, a fact that has previously been reported by other authors who have interpreted this as an expression of greater extension of the acute MI. 25 Our model has a sensitivity of only 28.4%, but we excluded those parameters appearing during hospitalization , which might have influenced mortality (with their inclusion it is logical to suppose that the sensitivity would have improved), since on designing the study we fixed as an objective the ability to make a prediction of mortality at the time of admission. Although the prognosis after acute MI has changed significantly since the introduction of thrombolytic drugs, this treatment has been systematically denied to patients older than 75 years (despite the fact that mortality among these is higher) because of the presentation of a greater number of complications. 26-31 According to the results obtained in recently published international multicentric studies, analyzing the behavior of different population groups in relation to this treatment, the use of an age limit as a restrictive criterion for the use of thrombolytic therapy cannot now be considered appropriate. In our group, the percentage of patients receiving this treatment is high (21.1%), despite which we have been unable to detect a significant favorable influence of this fact on mortality , which we believe to be due to the limited size of the sample.32- 44 Our data , therefore, agree with previous reports
regarding the consideration of the hemodynamic situation on admission, a greater extension of the acute MI, or female sex as factors predicting mortality . We believe that these results will enable us to delimit those patients who will obtain greater benefit from their admission to the CCU, as well as the use of thrombolytic or other aggressive therapy, both always difficult decisions in this age group. CONCLUSIONS
In patients older than 70 years of age, together with the degree of hemodynamic involvement and extension of the acute MI, sex and right bundle branch block are independent predictors of mortality on admission to the hospital. Age is no longer a predictive factor of mortality in these patients, so we do not believe the differentiation into old and very old patients is necessary. REFERENCES
1 De Fockert JA. De klinische presentatie van het acute myocardinfarct op hogere leeftijd. Tijdschr Gerontal Geriatr 1987; 18:305-08 2 Wenger NK, Fur berg CD, Pitt E. Coronary heart disease in the elderly: review of current knowledge and research recommendations. In: Wenger NK, Furberg CD, Pitt E, eds. Coronary heart disease in the elderly. New York: Elsevier, 1986; 1-7 3 Friedewald WT. Cardiovascular disease in the elderly. J Am Coli Cardiol1 987; 10(suppl A):7 A-BA 4 Adolph RJ. The elderly, the very elderly and traditional practice patterns. J Am Coli Cardiol 1990; 16:793-94 5 Sato H, Tateishi H, Uchida T, et al. Acute myocardial infarction in the elderly. Jpn Circ J 1988; 52:454-59 6 House MA. Thrombolytic therapy for acute myocardial infarction: the elderly population. AACN Clin Issues Crit Care Nurs 1992; 3:106-13 7 Ferriz J A,Vera A, Suarez G, et al. Sexo femenino y mortalidad tras infarto agudo de miocardia. Rev Esp Cardiol 1994; 46: 796-82 8 Tofler GH, Muller JE, Stone PH, eta!. Factors leading to shorter survival after acute myocardial infarction in patients aged 65 to 75 years com pared with younger patien ts. Am J Cardiol1988; 62:860-67 9 Weaver WD, Litwin PE, Martin JS, eta!. Effect of age on use of thrombolytic therapy and mortality in acute myocardial infarction: the MITI project group. J Am Coli Cardiol 1991 ; 18:657-62 10 Martinez Sande JL, Amaro Cendon A, Gonzalez Juanatey JR, et al. Implicaciones clinicas y pron6sticas de Ia edad en el infarto agudo de miocardio. Arch Inst Cardiol Mex 1991; 61:579-86 11 Hoit BD, Gilpin EA, Henning H , et al. Myocardial infarction in young patients: an analysis by age subsets. Circulation 1986; 74:712-21 12 Montague TJ, Ikuta RM, Wong RY, et a!. Comparison of risk and patterns of practice in patients older and younger than 70 years with acute myocardial infarction in a 2-year period (1987-1989). Am J Cardiol1991; 68:843-47 13 Garcia Rubira JC, Romero D, Garcia Martinez JT, eta!. Infarto agudo de miocardio en octogenarios. Med Intensiva 1991; 15:86-8 14 Olmsted WL, Groden DL, Silverman ME. Prognosis in surviCHEST / 108 / 1 / JULY, 1995
87
vors of acute myocardial infarction occurring at age 70 years or older. Am J Cardiol1987; 60:971-75 15 Castello R, Alegria E, Olmos L, et al. El infarto agudo de miocardia en pacientes mayores de 65 aiios. Rev Med Univ Navarra 1987; 31:81-4 16 Day JJ, Bayer AJ, Pathy MS, et al. Acute myocardial infarction: diagnostic difficulties and outcome in advanced old age. Age Ageing 1987; 16:239-43 17 Castello R, Alegria E, Merino A, et al. Effect of age on long-term prognosis of patients with myocardial infarction. Int J Cardiol 1988; 20:221-30 18 Yang XS, Willems JL, Pardaens J, et al. Acute myocardial infarction in the very elderly: a comparison with younger age groups. Acta Cardiol1987; 42:59-68 19 Schafer JH, Maurer A, Arntz HR, et al. Akuter Myokardinfarkt: Aspekte der veranderten Sterblichkeit auf der Intensivstation: Ergebnisse einer prospektiven Untersuchung der Jahre 1985 bis 1987. Dtsch Med Wochenschr 1989; 114:1143-48 20 Petretta M, Canonico V, Bianchi V, et al. Influenza dell'eta sulla prognosi a breve e medio termine nei pazienti con infarto acuto del miocardio. G Ita! Cardiol1991; 21:395-408 21 Chua TS, Koo CC, Tan AT, et al. Mortality trends in the coronary care unit. Ann Acad Med Singapore 1990; 19:3-8 22 Day JJ, Bayer AJ, ChadhaJS, et al. Myocardial infarction in old people: the influence of diabetes mellitus. J Am Geriatr Soc 1988; 36:791-94 23 Chaitman BR, Thompson B, Wittry MD, et al. The use of tissue-type plasminogen activator for acute myocardial infarction in the elderly: results from thrombolysis in myocardial infarction phase I, open label studies and the thrombolysis in myocardial infarction phase II pilot study: The TIM! investigators. J Am Coli Cardiol 1989; 14:1159-65 24 Wellens HJJ. Right ventricular infarction. N Engl J Med 1993; 328:1036-38 25 Martinez Sande JL, Casariego R, Alonso 0, et al. El infarto de miocardio en el paciente geriatrico: factores pron6sticos a corto y medio plazo. Rev Esp Cardiol1992; 45:365-73 26 Vogel JH, Setty RK, Coughlin BJ, et al. Intravenous streptokinase in acute myocardial infarction at the community hospital: a 6-year experience. Am J Cardiol 1988; 62:25K-27K 27 Pedro PC, Pereirinha A, Fiuza M, et al. Trombolise no enfarte agudo de miocardio no idoso: urn risco acrescido de ruptura cardiaca? Rev Port Cardiol1991; 10:133-39 28 White H, Cross D, Scott M, et al. Comparison of effects of thrombolytic therapy on left ventricular function in patients over with those under 60 years of age. Am J Cardiol1991; 67: 913-18 29 Pendlebury WW, Iole ED, Tracy RP, et al. Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Ann Neurol1991; 29:210-13 30 Fleming C, D'Agostino RB, Selker HP. Is coronary-care-unit admission restricted for elderly patients? a multicenter study.
88
Am J Public Health 1991; 81:1121-26 31 Cragg DR, Friedman HZ, Bonema JD, et al. Outcome of patients with acute myocardial infarction who are ineligible for thrombolytic therapy. Ann Intern Med 1991; 115:173-77 32 Maggioni AP, Franzosi MG, Santoro E, et al. The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio II (GISSI-2) and the International Study Group. N Engl J Med 1992; 327:1-6 33 ISIS-3 (Third International Study of Infarct Survival) Collaborative group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41 ,299 cases of suspected acute myocardial infarction. Lancet 1992; 339:753-70 34 Krumholz HM, Pasternak RC, Weinstein MC, et al. Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. N Engl J Med 1992; 327:7-13 35 Johnston FA, Dunn FG, Hogg KJ, et al. Thrombolytic therapy in acute myocardial infarction in the elderly. Gerontology 1987; 33:331-39 36 Goldberg RJ, Gore JM, Gurwitz JH, et al. The impact of age on the incidence and prognosis of initial acute myocardial infarction: the Worcester Heart Attack Study. Am Heart J 1989; 17:543-49 37 Muller DW, Topol EJ. Selection of patients with acute myocardial infarction for thrombolytic therapy. Ann Intern Med 1990; 113:949-60 38 Feldman RL, Kaizer J, Standley M. Initial treatment of patients with acute ischemic heart disease hospitalized in a community hospital. Am J Cardiol1991 ; 68:61C-66C 39 Kline EM. Clinical controversies surrounding thrombolytic therapy in acute myocardial infarction. Heart Lung 1990; 19:596-601 40 Grines CL, de Maria AN. Optimal utilization of thrombolytic therapy for acute myocardial infarction. J Am Coli Cardiol 1990; 16:223-31 41 AIMS trial study group. Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. Lancet 1988; 1:545-49 42 ISIS-2 Collaborative group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2:349-61 43 Hendra TJ, Marshall AJ. Increased prescription of thrombolytic treatment to elderly patients with suspected acute myocardial infarction associated with audit. BMJ 1992; 304:423-25 44 Althouse R, Maynard C, Cerqueira M, et al. The western Washington Myocardial Infarction Registry and Emergency Department Tissue Plasminogen Activator Treatment Trial. Am J Cardiol1990; 66:1298-1303
Clinical Investigations