Kaplan-Meier curves of 6-month survival in patients with non–ST elevation acute coronary syndrome (A) and in patients with ST elevation acute coronary syndrome (B).
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Moriel M, Behar S, Tzivoni D, Hod H, Boyko V, Gottlieb S. Management and Outcomes of Elderly Women and Men With Acute Coronary Syndromes in 2000 and 2002. Arch Intern Med. 2005;165(13):1521–1526. doi:10.1001/archinte.165.13.1521
Previous studies have suggested that women with myocardial infarction are treated less aggressively and have worse outcomes compared with men. The objective of this study was to evaluate sex differences in the management and outcomes of elderly (age ≥70 years) women and men with acute coronary syndromes (ACSs) in the new millennium.
This study includes 1331 consecutive elderly patients with ACSs admitted to all intensive coronary care units and cardiology departments in Israel from 2 prospective nationwide ACS surveys conducted in 2000 and 2002.
The mean age of women vs men was comparable (79 vs 78 years). Comorbidities were more frequent in women, whereas previous coronary disease and typical anginal pain on admission were more frequent in men. Medical treatments and revascularization procedures during the index hospitalization were comparable in both groups. Crude and covariate-adjusted mortality rates were higher in women at 7 days (12% vs 7%; P = .007; adjusted odds ratio [OR], 1.83; 95% confidence interval [CI], 1.15-2.91) but not at 6 months (21% vs 19%; adjusted OR, 1.10; 95% CI, 0.79-1.52). This difference was attributed to ST elevation (STE)–ACS in women vs men (19% vs 12%; P = .007; adjusted OR, 1.97; 95% CI, 1.14-3.46). Seven-day mortality rates were highest in patients with STE-ACS denied coronary angiography, especially women (23% vs 15%; P = .06).
In the 2000s, elderly women and men with ACSs are receiving similar medical and invasive management during the index hospitalization; however, women with STE-ACS have higher mortality rates at 7 days but not at 6 months. Mortality rates are highest in patients with STE-ACS denied coronary angiography. The benefit of invasive procedures on mortality rates in elderly patients with STE-ACS needs further investigation.
Several studies1-5 published during the early 1990s suggested that women with acute myocardial infarction (AMI) are older, are treated less aggressively than men, receive less medical therapy, and undergo fewer invasive procedures. However, among women and men enrolled in thrombolytic studies,6,7 sex-related treatment differences were not apparent. Sex differences in the management of patients with AMI were attributed mainly to the fact that women were older than men and more often had other comorbidities.8-13 Several previous studies have demonstrated that women with AMI experience worse outcomes than men owing to higher mortality rates,8-10,12-14 especially at a younger age,15 whereas in other studies,11 this difference in outcome vanished after covariate adjustment for age and comorbidities.
Studies that compare the management and outcomes of women and men, especially elderly individuals, with acute coronary syndromes (ACSs) of ST elevation (STE) and non-STE in unselected populations in the 2000s are scarce. The purpose of the present study is to evaluate sex differences in the treatment modalities and outcomes of elderly patients (age ≥70 years) with ACSs in the 2000s in a prospective, observational, community-based study.
The 1331 patients included in this study were derived from 2 prospective nationwide surveys conducted during 2-month periods (February and March) in 2000 and 2002 of all patients with ACSs admitted to all 26 intensive coronary care units (CCUs) and cardiology departments in Israel, as described elsewhere.16 The surveys were designed as prospective observational case series of all consecutive patients with ACSs with out age limit in all medical centers in the country. Demographic, historical, and clinical data; admission electrocardiography with STE and non-STE; the presence or absence of Q waves at discharge; medical therapies; invasive procedures; complications; and follow-up data were recorded on predefined forms by dedicated physicians. The diagnosis of ACS was laid down prospectively by the executive committee of the surveys, according to the usual clinical, electrocardiographic, and cardiac markers criteria.16 The organization, data acquisition, management, and follow-up were performed at the same coordinating center for the 2000 and 2002 surveys. Medical therapies and invasive procedures were determined in each CCU at the discretion of each center. Reasons for exclusion from reperfusion therapy (thrombolysis or percutaneous coronary intervention [PCI]) were recorded. On-site catheterization and coronary artery bypass grafting facilities were available in 23 and 12 of the 26 centers, respectively. Data checks for completeness and consistency were based on computerized data queries issued at the coordinating center of the Israel Society for the Prevention of Heart Attacks in Tel HaShomer and were completed from the medical reports attached to each patient form, as described elsewhere.11 Seven-day and 6-month mortality rates were assessed from hospital records or by matching the identification numbers of the patients with the Israeli National Population Register.
All analyses were performed using statistical software (SAS; SAS Institute Inc, Cary, NC). To determine the significance of the differences between proportions and means, χ2 and t tests, respectively, were used. Results of continuous variables are reported as mean ± SD. The nonparametric Wilcoxon test was used to compare the time from pain onset to thrombolytic therapy or PCI in women and men. Two-sided probability values are reported.
Seven-day mortality rates, 6-month mortality rates in 7-day survivors, and cumulative 6-month mortality rates in women and men were compared in terms of odds ratio (OR) and 95% confidence interval (CI) using logistic regression analysis (SAS LOGISTIC Procedure). In the mortality models for the entire cohort and for patients with non-STE–ACS, adjustment was performed for age, diabetes mellitus, hypertension, current smoking, previous MI, past revascularization, typical pain on hospital admission, Killip class II or higher on admission, first ward of hospitalization (CCU vs internal medicine ward), peak creatine kinase concentration, and coronary angiography performance. Similar variables were included in the mortality models for patients with STE-ACS, including the variables of reperfusion (primary PCI or thrombolysis). Survival curves were estimated using the Kaplan-Meier method. The significance of the difference between the survival curves was assessed using the log-rank test (SAS LIFETEST Procedure).
The study population included all 1331 patients 70 years or older (range, 71-102 years), which consisted of 37% of the 3577 patients from the 2 ACS surveys (1508 patients in 2000 and 2049 patients in 2002). The clinical characteristics of the 511 women (38%) and 820 men (62%) included in this study are summarized in Table 1. The mean age of women and men was similar. Diabetes mellitus, hypertension, and hyperlipidemia were more frequent in women vs men, whereas men were more frequently smokers and patients with chronic renal failure. Histories of previous angina pectoris, MI, and revascularization were less frequent in women.
Women and men who underwent coronary angiography were younger than their counterparts who did not (mean ± SD age: 77 ± 4 vs 80 ± 6 years in women and 77 ± 5 vs 80 ± 6 years in men). Women and men who underwent coronary angiography had previous PCI more often but had chronic renal failure and Killip class II or higher less often. The other clinical characteristics of women and men did not differ from those of the entire cohort whether they underwent coronary angiography or not.
Typical anginal pain on hospital admission was slightly less frequent in women. ST elevation on admission electrocardiography and a discharge diagnosis of Q wave MI were slightly more frequent in women than in men. Infarct size determined by peak creatine kinase level was comparable in both sexes.
Time from symptom onset to arrival at the emergency department was longer by 34 minutes in women (Table 2). Admission rates to the CCU as the first ward or transfer from internal medicine wards were similar in women and men. The medical and invasive managements, including coronary angiography, PCI, and coronary bypass surgery management, of women and men were comparable. The frequency of revascularization in patients who had coronary angiography was slightly lower in women than in men (73% vs 79%; P = .08). Among patients with STE-ACS, the frequency of acute reperfusion therapy, ie, thrombolysis or primary PCI, was similar in women and men.
In-hospital complications were comparable in both sexes, except for acute mitral regurgitation, which was more frequent in women (Table 3). At 30 days, 11% of women and men were rehospitalized urgently, whereas 5% and 6%, respectively, were rehospitalized electively for a cardiac cause.
For the entire cohort, crude and covariate-adjusted mortality rates were higher in women than in men at 7 days (12% vs 7%; P = .007; adjusted OR, 1.83; 95% CI, 1.15-2.91) but not at 6 months (21% vs 19%; adjusted OR, 1.10; 95% CI, 0.79-1.52) (Table 4). In the entire cohort, in patients who underwent coronary angiography, 7-day mortality rates were higher in women vs men (8% vs 3%; P = .01), a difference that vanished at 6 months (15% vs 12%; P = .17). Women and men who did not undergo coronary angiography had higher mortality rates at 7 days (15% vs 11%; P = .16) and at 6 months (26% vs 27%; P = .71). Use of coronary angiography was associated with better outcomes at 7 days (OR, 0.38; 95% CI, 0.23-0.62) and at 6 months (OR, 0.51; 95% CI, 0.37-0.71) in women and men.
Among patients with non-STE–ACS, crude and covariate-adjusted mortality rates were similar in women and men at 7 days (4% vs 4%; adjusted OR, 1.12; 95% CI, 0.43-2.79) and at 6 months (16% vs 15%; OR, 1.01; 95% CI, 0.61-1.65) (Table 4 and Figure, A). Among patients who underwent coronary angiography, a trend toward higher mortality rates at 7 days and 6 months was noted in women vs men (2% vs 0.4%; P = .09; and 12% vs 9%, respectively; P = .25). Women and men who did not undergo coronary angiography had higher mortality rates at 7 days (6% vs 8%; P = .45) and at 6 months (19% vs 22%; P = .46). Use of coronary angiography was associated with better outcomes at 7 days (OR, 0.19; 95% CI, 0.05-0.54) and at 6 months (OR, 0.62; 95% CI, 0.38-1.00) in women and men.
Among patients with STE-ACS, crude and covariate-adjusted mortality rates were significantly higher in women than in men at 7 days (19% vs 12%; P = .007; adjusted OR, 1.97; 95% CI, 1.14-3.46) (Table 4 and Figure, B); however, this difference vanished at 6 months (26% vs 25%; adjusted OR, 1.10; 95% CI, 0.69-1.76). Mortality rates at 7 days among patients with STE-ACS who underwent coronary angiography were higher in women than in men (14% vs 7%; P = .07). Women and men who did not undergo coronary angiography had higher mortality rates at 7 days, which were higher in women (23% vs 15%; P = .06). These sex differences in mortality vanished at 6 months among those who underwent coronary angiography (19% and 16%; P = .53) and those who did not (32% and 33%; P = .95). Use of coronary angiography was associated with better outcomes at 7 days (OR, 0.45; 95% CI, 0.25-0.80) and at 6 months (OR, 0.40; 95% CI, 0.25-0.64) in women and men.
Most early studies in the reperfusion era comparing management and outcomes of men and women with AMI found that women were less likely to be treated with thrombolysis and other medical therapies, including revascularization, but that most of theses differences did not persist after adjustment for age and other baseline characteristics.17 Studies that compare the management and outcomes of elderly women and men with ACSs in unselected populations in the 2000s are scarce, especially in the elderly.
This prospective, observational, community-based survey of consecutive elderly patients with ACSs in Israel in 2000 and 2002 revealed that women experience worse outcomes compared with men at 7 days but not at 6 months. The worse outcome at 7 days was noted in women with STE-ACS but not in those with non-STE–ACS. Women and men in this cohort were of similar age, but women more frequently had comorbidities and less frequently had previously known coronary artery disease. The time delay between the onset of symptoms and arrival at the emergency department was longer in elderly women than in elderly men. In-hospital management, including medical treatment and revascularization procedures, was similar in the 2 sexes.
This study reveals that one third of elderly patients of both sexes with ACSs experience heart failure or cardiogenic shock. Similar frequencies of life-threatening ventricular arrhythmias, advanced heart block, mitral regurgitation, and recurrent ischemia or infarction were also noted in this group of elderly women and men. These results are discordant to those of other studies7,9-11,14,15 performed in younger patient populations, which demonstrated higher frequencies of heart failure, cardiogenic shock, mitral regurgitation, and advanced heart block in women compared with men. However, few data are available on sex differences in the elderly.
In contrast to previous studies11,12,15 that demonstrated some sex differences in the medical treatment of patients with AMI, the elderly women and men in the present study received similar medical therapies, including aspirin, heparin, ticlopidine hydrochloride or clopidogrel bisulfate, β-blockers, angiotensin-converting enzyme inhibitors, diuretics, and statins.
Although several previous studies8,12,15-20 in the 1990s revealed that women with AMI were less likely to receive thrombolytic therapy even after adjustment for older age, comorbidities, and late hospital arrival, sex-related bias was not evident in the present study or in others.11,21,22 Although some previous studies2,3,5,8,10,12,15,23,24 also suggested that women with AMI were less likely than men to undergo coronary angiography, others4,6,11,25-27 did not demonstrate such a sex-dependent difference. In the present study, the frequency of coronary angiography and PCI during the index hospitalization were similarly high in older women and men, a fact that reflects changes in the practice of the management of patients with ACSs in recent years.
The present study demonstrated higher crude and covariate-adjusted mortality rates in elderly women with ACSs at 7 days but not at 6 months. These findings are in accordance with numerous previous studies3,6-11,14,15,17,28-31 that described higher unadjusted and adjusted early mortality rates among women after AMI compared with men. Adjustment for age and other clinical characteristics decreased the magnitude of the increased relative risk of women but did not eliminate it, except in previous studies.11,32
In a publication by Vaccarino et al,15 the risk of in-hospital mortality after AMI was twice as high among women younger than 50 years compared with men; however, the sex difference decreased with age and was not evident at 74 years or older. In accordance with previous studies,11,28,29,32 after the increased mortality at the early phase after AMI, women had a similar outcome as men at the late phase after AMI.
The present study revealed a worse early outcome in elderly women with STE-ACS compared with men after adjustment for comorbidities, whereas similar outcomes in both sexes were noted among elderly patients with non-STE–ACS. In a study by Hochman et al,10 a nonsignificant trend toward an increased risk of death or reinfarction among women with STE-ACS compared with men was observed (OR, 1.27; 95% CI, 0.98-1.63); however, this population was significantly younger than ours. In a recent publication by Hasdai et al,33 female sex was not independently associated with worse in-hospital mortality, irrespective of the ACS type; however, this study population was also younger than ours. The discordance between our study results and these studies may be explained by different prognoses in elderly populations compared with younger populations.
Although the rate of reperfusion procedures (primary PCI and thrombolysis) among elderly patients with STE-ACS was relatively high (47%) in women and men, the mortality rates at 7 days (19% and 12%) and at 6 months (26% vs 25%) were high. It would have been expected that the high revascularization rate would improve the survival of patients with STE-ACS; the benefit of these procedures on mortality in this older population is not clear34 and should be further investigated.
The present study included elderly patients with ACSs who were hospitalized in all CCUs in Israel but not those who died before arrival or at the emergency department or those who were hospitalized in internal medicine wards. The decision to admit patients with ACSs to CCUs was left to the discretion of each center and to bed availability; hence, it is conceivable that older patients were admitted more frequently to internal medicine wards, as described earlier.35 Also, the decision to perform coronary angiography was left to the discretion of each center, and the reason for not performing coronary angiography was not registered in the survey. Thus, we could not differentiate between patients who refused angiography and those who were “denied” the procedure. Differences in referral may reflect different preferences for sicker patients. Nonetheless, this retrospective analysis represents the management and outcomes of elderly women and men with ACSs in “real life.”
This prospective observational survey of consecutive elderly patients with ACSs in Israel in 2000 and 2002 revealed that patients of both sexes, especially those with STE-ACS, have high mortality rates at the early and late phases. Elderly women with STE-ACS fare worse than men early after the event but not thereafter. Sex differences in treatment modalities were not apparent in this cohort and were characterized by a high revascularization rate. The benefit of invasive procedures on the mortality outcome in elderly patients with STE-ACS should be further studied.
Correspondence: Mady Moriel, MD, Department of Cardiology, Shaare Zedek Medical Center, 12 Hans Beyth St, PO Box 3235, Jerusalem 91031, Israel (firstname.lastname@example.org).
Accepted for Publication: December 3, 2004.
Previous Presentation: This study was presented in part at the American College of Cardiology Scientific Sessions; March 3, 2004; New Orleans, La.
Acknowledgment: We thank the Israel Society for the Prevention of Heart Attacks, the Working Group on Intensive Cardiac Care of the Israel Heart Society, and the Israel Center for Disease Control, Tel Aviv, and Sherri Aharoni for her technical support.
Financial Disclosure: None.