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Coronary care units. A perspective on their epidemiologic impact
284
9 Maroko PR, Hillis LD, Muller JE et al. Favourable effects of hyaluronidase on electrocardiographic evidence of necrosis in patients with acute myocardial infarction. N Engl J Med 1977; 296: 898-903. General Hospital Steelhouse Lane Birmingham
Brian L. Pentecost
84, England
Coronary care units. A perspective on their epidemiologic impact As coronary care units (CCUs) celebrate their twentieth anniversary, a look at their impact on patients with acute myocardial infarction is warranted. Are such units a major contributor to the declining mortality rate from ischemic heart disease in the United States? Or, are they expensive innovations with minimal impact? Historical perspective Coronary care units were introduced nearly simultaneously in the United States, Canada, and Australia in the early 1960s in an attempt to lower the previously standard 35% mortality among hospital admissions with acute myocardial infarctions. Because each of the original reports of CCUs included patients who were resuscitated from previously fatal arrhythmias, CCUs quickly gained wide popularity. The first trials of the efficacy of CCUs seemed to substantiate the early uncontrolled observations. Marshall [l] showed a lower mortality and a higher rate of successful resuscitation among patients in a general hospital with a CCU than among concurrent patients treated by the same physicians in the same city at a Veterans Administration Hospital without a CCU. Two non-randomized Scandinavian studies [2,3] compared hospitalized ward patients to concurrent CCU patients and showed lower mortalities in the CCU, especially during the first 24 hours after admission. Norris [4] tested his coronary prognostic index on patients in two hospitals, only one of which had a CCU, and found that the CCU significantly reduced mortality in moderately ill (Norris score of 6- 10 points) patients. However, CCU mortality was not significantly lower than the mortality had been in the previous year at the same hospital when a well-organized resuscitation team had been available for the hospital wards. Norris endorsed CCUs mainly because he felt that the original results of resuscitation on the hospital wards would be hard to “ undeniable” logic of centralized monitoring and sustain, and because of the resuscitation facilities. Subsequent studies, however, have seriously disputed the results of these earlier reports. Mather et al. [5] randomized 24% of 1895 patients to home versus hospital care because they were under age 70, had adequate home situations, and did not have any medical conditions that were felt by their physicians to make randomizaInternational Journal of Cardiology, 2 (1982) 284-287 0 Elsevier Biomedical Press
285
tion inappropriate. In these selected patients, survival at 330 days was slightly better among patients randomized to home care. In another study, Hill et al. [6] sent a hospital-based medical team to the homes of 500 patients, 50% of whom were seen within 3 hours of the onset of symptoms. Patients were observed at home for 2 hours, and 349 (70%) were then randomized to home versus hospital care because they had not required resuscitation, had no complications or coincidental diseases requiring hospital admission, and had a suitable social situation for home care. At follow-up 6 weeks later, the mortality was 13% in the home group and 11% in the hospital group. There were significantly more deaths during the first 24 hours in the home care group, but several of the hospital patients who were resuscitated during the first 24 hours died subsequently during the admission. Another 8 patients were resuscitated in their homes by the study team and were never randomized. Epidemiologic perspective Given these conflicting data, is there some underlying logic to explain why two moderate-sized randomized controlled trials have not shown benefits from CCUs, yet randomized trials would be considered unethical by many experts in the United States? To explore this paradox, we must analyze some additional epidemiologic data. The highest risk of sudden death from acute myocardial infarction is in the first hours after the onset of symptoms and then declines exponentially [7]. Colling et al. [B] found that half of the deaths from acute myocardial infarction occurred nearly immediately and another 21% occurred within the next 2 hours. Because the median delay from the onset of symptoms to the arrival of medical care is 3 hours in the best of studies [6,8], 70% of the deaths from acute myocardial infarction may occur before patients come to medical care. Thus, Rose [9] estimated that CCUs probably could reduce the mortality from acute myocardial infarction by no more than 58, a figure that roughly corresponds to the percentage of patients with acute myocardial infarctions who will develop primary ventricular fibrillation in the absence of overwhelming heart failure after hospital arrival [lo]. Our own data are consistent with Rose’s estimates. Between 1973 and 1978, a period after CCUs may have contributed to a decline in sudden arrhythmic deaths, CCU care for patients with acute myocardial infarction did not contribute to the reduction in ischemic heart disease mortality in a defined geographical area near Boston, Massachusetts [ll]. Thus, the monitoring and nursing facilities of CCUs may reduce in-hospital sudden. deaths, but at present there are no data to suggest that the many subsequent innovations have substantially contributed to the decline in United States mortality rates even though they may occasionally and dramatically save individual patients. If CCUs truly reduced mortality rates from 15 to IO%, a study would need a sample size of 1800 patients to have a 90% chance of demonstrating a statistically significant reduction in mortality in the CCU group. But if such a difference existed, hospital care would save nearly 9000 lives each year in the United States. If the actual benefit from CCUs is smaller, for example, to reduce mortality from 13 to
286
11% as in the Hill study [6], a sample size of 11000 patients might be needed to show statistical significance, and CCUs would save about 3500 Americans each year. Thus, the British randomized trials [5,6] might not be of sufficient size to show the benefits of CCUs, and the potential risks to the population as a whole are substantial if we are being misled by studies which may be too small to detect clinically-important differences. Suggested roles for coronary care units Thus, the reasons for the divergent opinions on the value of CCUs seem clearer. CCUs are likely to reduce sudden arrhythmic death rates in the early phase of acute myocardial infarction, and they are most efficacious in patients who arrive within 2 or at most 6 hours after the onset of symptoms. In patients who arrive within 6 hours of the onset of pain, lidocaine in sufficient doses appears to reduce the risk of ventricular fibrillation [ 121. Such lidocaine doses probably cannot be given as safely in non-intensive care settings. If, as in the Hill study [6], it is practical to send a team to a patient’s house for observation until about 6 hours have elapsed since the onset of symptoms, a patient will be beyond the highest risk period for arrhythmias, and home care may be as safe as hospital care. Hospitalization could then be reserved for patients who had other complications that might require hospital care, although I personally believe that monitoring and resuscitative facilities ideally should be available for 24 hours [lo]. Conversely, in a country like the United States, where house calls are rarely if ever performed, the institution of such a system solely for patients with acute chest pain may be impractical, and immediate hospital transfer is much more feasible and probably safer. However, CCU care need not extend for 3 full days because virtually all of the routine benefits of the CCU for uncomplicated patients will be gleaned in the first 24 hours. For uncomplicated patients who are admitted more than 24 hours after the onset of symptoms or in whom the probability of an acute infarction is perhaps 5% or less, admission to a well-staffed hospital ward may be nearly as effective and far less costly than admission to a CCU. Finally, the utility of out-of-hospital resuscitation by lay citizens and paramedics cannot be underestimated. Among patients who are resuscitated on the streets, approximately 30% will survive to leave the hospital, and patients who survive to leave the hospital have a 4-year ‘survival of about 50% [ 131. In the future, CCUs may be used routinely for infarct size reduction, the intracoronary injection of streptokinase, or other interventions. However, these potential uses of CCU resources remain investigational, and the only proved benefit of CCUs is the prevention or treatment of sudden fatal arrhythmias. Even the treatment of myocardial infarction complicated by heart failure, using afterload reduction, vasopressors, or intra-aortic balloon counterpulsation, has limited benefits. Individual lives may be saved, but such interventions appear not to have substantially contributed to a decline in overall mortality rates in the population as a whole [ 111.
287
References 1 Marshall RM, Blount SG, Genton E. Acute myocardial infarction: influence of a coronary care unit. Arch Intern Med 1968; 122: 473-475. S. Influence of treatment in a CCU on prognosis in acute myocardial infarction. Acta 2 Hofvendahl Med Stand (Suppl) 1971; 519: l-78. 3 Christensen I, Iverson K, Skouby AP. Benefits obtained by the introduction of a coronary-care unit. Acta Med Stand 1971; 189: 285-291. 4 Norris RM, Brandt PWT, Lee AJ. Mortality in a coronary-care unit analysed by a new coronary prognostic index. Lancet 1969; 1: 278-281. 5 Mather HG, Morgan DC, Pearson NG, et al. Myocardial infarction: a comparison between home and hospital care for patients. Br Med J 1976; 1: 925-929. JR, Mitchell JRA. A randomized trial of home-versus-hospital management for 6 Hill JD, Hampton patients with suspected myocardial infarction. Lancet 1978; 1: 837-841. 7 Adgey AAJ, Geddes JS, Webb SW, et al. Acute phase of myocardial infarction. Lancet 1971: 2: 50 I-504. 8 Colling A. Dellipiani AW, Donaldson RJ, MacCormack P. Teesside coronary survey: an epidemiological study of acute attacks of myocardial infarction. Br Med J 1976; 2: 1169-l 172. Rose G. The contribution of intensive coronary care. Br J Prev Sot Med 1975; 29: 147-150. Goldman L, Batsford WP. Risk-benefit stratification as a guide to lidocaine prophylaxis of primary ventricular fibrillation in acute myocardial infarction: an analytic review. Yale J Biol Med 1979; 52: 455-466. Goldman L, Cook F, Hashimoto B, Stone P. Muller J. Loscalzo A. Evidence that hospital care for acute myocardial infarction has not contributed to the decline in coronary mortality between 1973-1974 and 1978-1979. Circulation 1982; 65: 936-942. Lie KI, Wellens HJ, Van Capelle FJ. Durrer D. Lidocaine in the prevention of primary ventricular fibrillation. N Engl J Med 1974; 291: 1324-1326. Eisenberg MS, Hallstrom A, Bergner L. Long-term survival after out-of-hospital cardiac arrest. New Engl J Med 1982; 306: 1340- 1343. Department of Medicine Brigham and Women’s Hospital 75 Francis Street Boston, MA 02115. U.S.A.
Lee Goldman
*
Mode of development of calcific aortic stenosis and its clinical implications Paul Wood in his classic paper [l] analyzed 250 cases of aortic stenosis; he considered as the etiological factor congenital heart disease in 20% and rheumatic heart disease in 80% of cases. A new approach to the etiology of aortic stenosis was introduced later by Edwards [2] who postulated that calcific aortic stenosis may be related to a nonspecific degenerative process involving aortic valve cusps either congenitally deformed or mildly damaged by acquired processes. The commonest mechanism for aortic stenosis of old age according to this view is a congenital * Dr. Goldman Kaiser
Family
is a teaching Foundation
and research scholar of the American College of Physicians Scholar in Genera1 Internal Medicine.
International Journal of Cardiology. 2 (1982) 287-291 0 Elsevier Biomedical Press
and a Henry J.
9 Maroko PR, Hillis LD, Muller JE et al. Favourable effects of hyaluronidase on electrocardiographic evidence of necrosis in patients with acute myocardial infarction. N Engl J Med 1977; 296: 898-903. General Hospital Steelhouse Lane Birmingham
Brian L. Pentecost
84, England
Coronary care units. A perspective on their epidemiologic impact As coronary care units (CCUs) celebrate their twentieth anniversary, a look at their impact on patients with acute myocardial infarction is warranted. Are such units a major contributor to the declining mortality rate from ischemic heart disease in the United States? Or, are they expensive innovations with minimal impact? Historical perspective Coronary care units were introduced nearly simultaneously in the United States, Canada, and Australia in the early 1960s in an attempt to lower the previously standard 35% mortality among hospital admissions with acute myocardial infarctions. Because each of the original reports of CCUs included patients who were resuscitated from previously fatal arrhythmias, CCUs quickly gained wide popularity. The first trials of the efficacy of CCUs seemed to substantiate the early uncontrolled observations. Marshall [l] showed a lower mortality and a higher rate of successful resuscitation among patients in a general hospital with a CCU than among concurrent patients treated by the same physicians in the same city at a Veterans Administration Hospital without a CCU. Two non-randomized Scandinavian studies [2,3] compared hospitalized ward patients to concurrent CCU patients and showed lower mortalities in the CCU, especially during the first 24 hours after admission. Norris [4] tested his coronary prognostic index on patients in two hospitals, only one of which had a CCU, and found that the CCU significantly reduced mortality in moderately ill (Norris score of 6- 10 points) patients. However, CCU mortality was not significantly lower than the mortality had been in the previous year at the same hospital when a well-organized resuscitation team had been available for the hospital wards. Norris endorsed CCUs mainly because he felt that the original results of resuscitation on the hospital wards would be hard to “ undeniable” logic of centralized monitoring and sustain, and because of the resuscitation facilities. Subsequent studies, however, have seriously disputed the results of these earlier reports. Mather et al. [5] randomized 24% of 1895 patients to home versus hospital care because they were under age 70, had adequate home situations, and did not have any medical conditions that were felt by their physicians to make randomizaInternational Journal of Cardiology, 2 (1982) 284-287 0 Elsevier Biomedical Press
285
tion inappropriate. In these selected patients, survival at 330 days was slightly better among patients randomized to home care. In another study, Hill et al. [6] sent a hospital-based medical team to the homes of 500 patients, 50% of whom were seen within 3 hours of the onset of symptoms. Patients were observed at home for 2 hours, and 349 (70%) were then randomized to home versus hospital care because they had not required resuscitation, had no complications or coincidental diseases requiring hospital admission, and had a suitable social situation for home care. At follow-up 6 weeks later, the mortality was 13% in the home group and 11% in the hospital group. There were significantly more deaths during the first 24 hours in the home care group, but several of the hospital patients who were resuscitated during the first 24 hours died subsequently during the admission. Another 8 patients were resuscitated in their homes by the study team and were never randomized. Epidemiologic perspective Given these conflicting data, is there some underlying logic to explain why two moderate-sized randomized controlled trials have not shown benefits from CCUs, yet randomized trials would be considered unethical by many experts in the United States? To explore this paradox, we must analyze some additional epidemiologic data. The highest risk of sudden death from acute myocardial infarction is in the first hours after the onset of symptoms and then declines exponentially [7]. Colling et al. [B] found that half of the deaths from acute myocardial infarction occurred nearly immediately and another 21% occurred within the next 2 hours. Because the median delay from the onset of symptoms to the arrival of medical care is 3 hours in the best of studies [6,8], 70% of the deaths from acute myocardial infarction may occur before patients come to medical care. Thus, Rose [9] estimated that CCUs probably could reduce the mortality from acute myocardial infarction by no more than 58, a figure that roughly corresponds to the percentage of patients with acute myocardial infarctions who will develop primary ventricular fibrillation in the absence of overwhelming heart failure after hospital arrival [lo]. Our own data are consistent with Rose’s estimates. Between 1973 and 1978, a period after CCUs may have contributed to a decline in sudden arrhythmic deaths, CCU care for patients with acute myocardial infarction did not contribute to the reduction in ischemic heart disease mortality in a defined geographical area near Boston, Massachusetts [ll]. Thus, the monitoring and nursing facilities of CCUs may reduce in-hospital sudden. deaths, but at present there are no data to suggest that the many subsequent innovations have substantially contributed to the decline in United States mortality rates even though they may occasionally and dramatically save individual patients. If CCUs truly reduced mortality rates from 15 to IO%, a study would need a sample size of 1800 patients to have a 90% chance of demonstrating a statistically significant reduction in mortality in the CCU group. But if such a difference existed, hospital care would save nearly 9000 lives each year in the United States. If the actual benefit from CCUs is smaller, for example, to reduce mortality from 13 to
286
11% as in the Hill study [6], a sample size of 11000 patients might be needed to show statistical significance, and CCUs would save about 3500 Americans each year. Thus, the British randomized trials [5,6] might not be of sufficient size to show the benefits of CCUs, and the potential risks to the population as a whole are substantial if we are being misled by studies which may be too small to detect clinically-important differences. Suggested roles for coronary care units Thus, the reasons for the divergent opinions on the value of CCUs seem clearer. CCUs are likely to reduce sudden arrhythmic death rates in the early phase of acute myocardial infarction, and they are most efficacious in patients who arrive within 2 or at most 6 hours after the onset of symptoms. In patients who arrive within 6 hours of the onset of pain, lidocaine in sufficient doses appears to reduce the risk of ventricular fibrillation [ 121. Such lidocaine doses probably cannot be given as safely in non-intensive care settings. If, as in the Hill study [6], it is practical to send a team to a patient’s house for observation until about 6 hours have elapsed since the onset of symptoms, a patient will be beyond the highest risk period for arrhythmias, and home care may be as safe as hospital care. Hospitalization could then be reserved for patients who had other complications that might require hospital care, although I personally believe that monitoring and resuscitative facilities ideally should be available for 24 hours [lo]. Conversely, in a country like the United States, where house calls are rarely if ever performed, the institution of such a system solely for patients with acute chest pain may be impractical, and immediate hospital transfer is much more feasible and probably safer. However, CCU care need not extend for 3 full days because virtually all of the routine benefits of the CCU for uncomplicated patients will be gleaned in the first 24 hours. For uncomplicated patients who are admitted more than 24 hours after the onset of symptoms or in whom the probability of an acute infarction is perhaps 5% or less, admission to a well-staffed hospital ward may be nearly as effective and far less costly than admission to a CCU. Finally, the utility of out-of-hospital resuscitation by lay citizens and paramedics cannot be underestimated. Among patients who are resuscitated on the streets, approximately 30% will survive to leave the hospital, and patients who survive to leave the hospital have a 4-year ‘survival of about 50% [ 131. In the future, CCUs may be used routinely for infarct size reduction, the intracoronary injection of streptokinase, or other interventions. However, these potential uses of CCU resources remain investigational, and the only proved benefit of CCUs is the prevention or treatment of sudden fatal arrhythmias. Even the treatment of myocardial infarction complicated by heart failure, using afterload reduction, vasopressors, or intra-aortic balloon counterpulsation, has limited benefits. Individual lives may be saved, but such interventions appear not to have substantially contributed to a decline in overall mortality rates in the population as a whole [ 111.
287
References 1 Marshall RM, Blount SG, Genton E. Acute myocardial infarction: influence of a coronary care unit. Arch Intern Med 1968; 122: 473-475. S. Influence of treatment in a CCU on prognosis in acute myocardial infarction. Acta 2 Hofvendahl Med Stand (Suppl) 1971; 519: l-78. 3 Christensen I, Iverson K, Skouby AP. Benefits obtained by the introduction of a coronary-care unit. Acta Med Stand 1971; 189: 285-291. 4 Norris RM, Brandt PWT, Lee AJ. Mortality in a coronary-care unit analysed by a new coronary prognostic index. Lancet 1969; 1: 278-281. 5 Mather HG, Morgan DC, Pearson NG, et al. Myocardial infarction: a comparison between home and hospital care for patients. Br Med J 1976; 1: 925-929. JR, Mitchell JRA. A randomized trial of home-versus-hospital management for 6 Hill JD, Hampton patients with suspected myocardial infarction. Lancet 1978; 1: 837-841. 7 Adgey AAJ, Geddes JS, Webb SW, et al. Acute phase of myocardial infarction. Lancet 1971: 2: 50 I-504. 8 Colling A. Dellipiani AW, Donaldson RJ, MacCormack P. Teesside coronary survey: an epidemiological study of acute attacks of myocardial infarction. Br Med J 1976; 2: 1169-l 172. Rose G. The contribution of intensive coronary care. Br J Prev Sot Med 1975; 29: 147-150. Goldman L, Batsford WP. Risk-benefit stratification as a guide to lidocaine prophylaxis of primary ventricular fibrillation in acute myocardial infarction: an analytic review. Yale J Biol Med 1979; 52: 455-466. Goldman L, Cook F, Hashimoto B, Stone P. Muller J. Loscalzo A. Evidence that hospital care for acute myocardial infarction has not contributed to the decline in coronary mortality between 1973-1974 and 1978-1979. Circulation 1982; 65: 936-942. Lie KI, Wellens HJ, Van Capelle FJ. Durrer D. Lidocaine in the prevention of primary ventricular fibrillation. N Engl J Med 1974; 291: 1324-1326. Eisenberg MS, Hallstrom A, Bergner L. Long-term survival after out-of-hospital cardiac arrest. New Engl J Med 1982; 306: 1340- 1343. Department of Medicine Brigham and Women’s Hospital 75 Francis Street Boston, MA 02115. U.S.A.
Lee Goldman
*
Mode of development of calcific aortic stenosis and its clinical implications Paul Wood in his classic paper [l] analyzed 250 cases of aortic stenosis; he considered as the etiological factor congenital heart disease in 20% and rheumatic heart disease in 80% of cases. A new approach to the etiology of aortic stenosis was introduced later by Edwards [2] who postulated that calcific aortic stenosis may be related to a nonspecific degenerative process involving aortic valve cusps either congenitally deformed or mildly damaged by acquired processes. The commonest mechanism for aortic stenosis of old age according to this view is a congenital * Dr. Goldman Kaiser
Family
is a teaching Foundation
and research scholar of the American College of Physicians Scholar in Genera1 Internal Medicine.
International Journal of Cardiology. 2 (1982) 287-291 0 Elsevier Biomedical Press
and a Henry J.