Abstract
BACKGROUND:
Studies before the turn of the century reported sex differences in procedure rates. It is unknown whether these differences persist.
OBJECTIVES:
To examine time trends and sex differences in coronary catheterization and revascularization following acute myocardial infarction (AMI).
METHODS:
A retrospective analysis was performed of all patients 20 years of age or older who were admitted to hospital in British Columbia with an AMI between April 1, 1994, and March 31, 2003. Segmented regression analysis was used to examine the inflection point of the time trend in 90-day catheterization rates post-AMI. Multivariable Cox regression modelling was used to evaluate sex differences in receiving catheterization and revascularization following AMI.
RESULTS:
Ninety-day coronary catheterization rates increased significantly over the study period for both men and women (P<0.0001 for trend), with a steeper increase beginning in September 2000. Women were less likely to undergo catheterization than men, even after adjustment for baseline differences; this sex effect was modified by age and care in the intensive care unit or cardiac care unit (ICU/CCU). Specifically, ICU/CCU admission eliminated the sex difference among patients who were younger than 65 years of age. Conditional on receiving cardiac catheterization post-AMI, female sex was not associated with a lower likelihood of receiving revascularization within one year (HR 0.96; 95% CI 0.91 to 1.02).
CONCLUSIONS:
Despite recent increases in catheterization rates post-AMI, women were less likely to undergo catheterization than men. Interestingly, access to ICU/CCU care removed the sex difference in catheterization access in patients younger than 65 years of age.
Keywords: Acute myocardial infarction, Cardiac catheterization, Revascularization, Sex
Abstract
HISTORIQUE :
Les études menées au tournant du siècle faisaient état de différences de taux d’interventions selon les sexes. On ne sait pas si ces différences persistent.
OBJECTIFS :
Examiner les tendances dans le temps et les différences selon les sexes du cathétérisme coronarien et de la revascularisation après un infarctus aigu du myocarde (IAM).
MÉTHODOLOGIE :
Les chercheurs ont procédé à une analyse rétrospective de tous les patients de 20 ans ou plus hospitalisés en Colombie-Britannique en raison d’un IAM entre le 1er avril 1994 et le 31 mars 2003. L’analyse de régression segmentée a permis d’examiner le point d’inflexion de la tendance dans le temps des taux de cathétérisme 90 jours après un IAM. Le modèle de régression de Cox multivariable a permis d’évaluer les différences d’administration de cathétérisme et de revascularisation selon les sexes après un IAM.
RÉSULTATS :
Les taux de cathétérismes coronaires au bout de 90 jours ont considérablement augmenté pendant la période de l’étude, tant chez les hommes que chez les femmes (P<0,0001 en matière de tendance), l’augmentation étant plus marquée à compter de septembre 2000. Les femmes étaient moins susceptibles de subir un cathétérisme que les hommes, même après rajustement des différences de départ. Cet effet attribuable au sexe changeait selon l’âge et les soins à l’unité de soins intensifs ou de soins cardiaques (USI-USC). Notamment, l’hospitalisation à l’USI-USC éliminait la différence selon les sexes chez les patients de moins de 65 ans. Sous réserve d’avoir reçu un cathétérisme cardiaque après l’IAM, le sexe féminin ne s’associait pas à une diminution de la probabilité d’avoir reçu une revascularisation au bout d’un an (FC 0,96; 95 % IC 0,91 à 1,02).
CONCLUSIONS :
Malgré l’augmentation récente du taux de cathétérisme après un IAM, les femmes étaient moins susceptibles de subir un cathétérisme que les hommes. Fait intéressant, l’accès à l’USI-USC faisait disparaître la différence d’accès au cathétérisme chez les patients de moins de 65 ans.
Studies published before 1999 have reported sex differences in cardiovascular procedure rates following an acute myocardial infarction (AMI). Specifically, women underwent coronary catheterization and revascularization less frequently than men (1–6). Age-adjusted mortality rates were significantly higher in women (4–6). After 1999, several trials were published demonstrating improved outcomes in patients receiving an early invasive strategy (coronary catheterization with or without percutaneous coronary intervention [PCI]) compared with a conservative approach following non-ST elevation myocardial infarction (NSTEMI) (7–9). In addition, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of patients with NSTEMI emphasized an early invasive approach in both men and women (10).
It is unknown whether sex differences in cardiac procedure rates post-AMI persist in the era emphasizing an early invasive strategy. We sought to examine trends in catheterization and revascularization rates following an AMI in British Columbia (BC) from 1994 to 2003. Specifically, we examined the effect of sex on receiving catheterization and revascularization adjusted for potential confounders.
METHODS
Study populations
Two patient cohorts were studied. The first cohort (the AMI cohort) included 47,535 patients (20 years of age or older) who were admitted to hospital with a diagnosis of AMI between April 1, 1994, and March 31, 2003, in BC. Data were extracted from the BC Hospitalization Database, which includes data on all hospital admissions in BC and all cardiac catheterization procedures, both inpatient and outpatient. An AMI was defined according to the WHO’s International Statistical Classification of Diseases and Related Health Problems, Ninth Revision coding system. All patients with a primary discharge diagnosis of AMI (410.x) with at least two days of stay in the hospital were eligible. A total of 5625 patients who had a previous AMI or previous catheterization, PCI or coronary artery bypass grafting (CABG) within one year of the index AMI were excluded because previous AMIs and cardiac procedures can affect the likelihood of receiving catheterization. Also, 1031 patients who died within the first two days of the index AMI admission date were excluded because of insufficient time to start treatments. After all exclusions, the final AMI cohort comprised 40,879 patients. The primary outcome was time to catheterization within one year of the index AMI.
The database used in the present analysis does not distinguish between ST elevation myocardial infaction (STEMI) and NSTEMI within the AMI diagnosis. Therefore, analyses were limited by the inability to distinguish between STEMI and NSTEMI patients in the present cohort. It is recognized that significantly fewer women than men present with ST elevation (27% versus 37%) (11). In addition, the recent literature supporting an early invasive strategy describes the NSTEMI population only. Despite these limitations, the results of the present study are important, particularly with regard to the interplay between sex, age and access to an intensive care unit or cardiac care unit (ICU/CCU). In addition, there is no evidence that there have been any changes in the proportion of patients with NSTEMI over time. Therefore, the data trend is still of importance.
In the second study cohort (the catheterization cohort), the aim was to evaluate the utilization of PCI or CABG by using the Cardiac Services BC Registry (CSBCR), a data set that includes substantive clinical detail, including coronary anatomy and ejection fraction. The CSBCR is a detailed prospective clinical registry of all cardiac procedures performed in BC. The present catheterization study cohort comprised 9531 patients with an AMI between May 1, 1999, and March 31, 2003, who underwent coronary catheterization within one year of their index AMI. A total of 298 patients with a normal angiogram were excluded, resulting in a final catheterization cohort of 9233 patients. The primary outcome of interest was sex differences in receiving revascularization (PCI or CABG) within one year of the index catheterization among patients with angiographic evidence of coronary artery disease (CAD).
Definitions
Index AMI admission was defined as the first AMI admission between April 1, 1994, and March 31, 2003, based on discharge diagnosis from hospital. Index coronary catheterization was defined as the first catheterization following the index AMI admission. Case complexity was defined according to the grouping methodology of the Canadian Institute for Health Information, which uses a four-level resource utilization index (1 = no complexity; 2 = complexity related to chronic conditions; 3 = complexity related to serious/important conditions; and 4 = complexity related to potentially life-threatening conditions).
Statistical analyses
Univariate comparisons of baseline characteristics between men and women were conducted using the χ2 test. Time trend analysis for 90-day catheterization rates was conducted using the Mantel-Haenszel χ2 test. The inflection point of the time trend in 90-day catheterization rates was also examined using the segmented regression model. Ninety days was chosen as the cut-off for catheterization rate analysis because the majority of catheterizations post-AMI were expected to be performed within 90 days.
Kaplan-Meier estimates and the log-rank test were used to evaluate the univariate association between sex and receiving catheterization within one year after index AMI admission. In the AMI cohort, a Cox regression model was used to evaluate the sex effect on receiving catheterization, adjusted for potential confounders including age, renal disease, congestive heart failure (CHF), cerebrovascular disease (CVD), diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), peripheral vascular disease (PVD), hypertension, hyperlipidemia, liver disease, cancer, presentation with shock or ventricular fibrillation arrest, ICU/CCU use, admission year, hospital category (with or without catheterization facilities), physician specialty, case complexity level and neighbourhood income. Physician specialty was classified into three categories – cardiologist, internist, and general practitioner or other physician type – based on the specialty of the most responsible physician at the index AMI admission. The set of potential confounders was selected based on clinical relevance among all available risk factors in the BC Hospitalization Database. The interactions between sex and age, sex and ICU/CCU use, and sex and year of AMI admission were also examined.
In the catheterization cohort (ie, patients who underwent catheterization within one year of their index AMI), a Cox regression model was used to examine the association between sex and receiving revascularization within one year of index catheterization. This was adjusted for age, extent of CAD, ejection fraction, DM, CHF, renal disease, hyperlipidemia, hypertension, PVD, CVD, COPD, liver disease, cancer, neighbourhood income group and catheterization year. The set of potential confounders was selected based on clinical relevance of all available risk factors in the CSBCR. The interactions between sex and age, and between sex and catheterization year were also examined.
All statistical analyses were performed using SAS version 9 (SAS Institute Inc, USA) and R version 2.2.1 (an open-source statistical language).
RESULTS
Sex differences in coronary catheterization rates post-AMI
Women comprised 34.3% of the AMI cohort. Women were older and had significantly more hypertension, DM, CHF, CVD, COPD and shock, and a higher case complexity level than men. In contrast, men tended to have more hyperlipidemia. Women 75 years of age or older were significantly less likely to access ICU/CCU care compared with men 75 years of age or older (56.6% versus 62.7%). Women were more likely to live in low-income neighborhoods than men (47.4% versus 41.0%) (Table 1).
TABLE 1.
Baseline characteristics of acute myocardial infarction patients by sex (n=40,879)
| Characteristics | Women (n=14,038) | Men (n=26,841) | P |
|---|---|---|---|
| Age, years | <0.01 | ||
| <55 | 8.1 | 19.8 | |
| 55–64 | 12.5 | 22.0 | |
| 65–74 | 25.3 | 27.1 | |
| ≥75 | 54.2 | 31.4 | |
| Diabetes | 20.8 | 17.1 | <0.01 |
| Heart failure | 27.0 | 17.6 | <0.01 |
| Renal disease | 2.8 | 2.7 | 0.58 |
| Hyperlipidemia | 5.5 | 7.0 | <0.01 |
| Hypertension | 27.9 | 21.1 | <0.01 |
| Peripheral vascular disease | 1.4 | 1.5 | 0.28 |
| Cerebrovascular disease | 3.8 | 2.9 | <0.01 |
| Pulmonary disease | 8.9 | 8.0 | <0.01 |
| Liver disease | 0.1 | 0.2 | 0.28 |
| Cancer | 0.1 | 0.0 | 0.04 |
| Shock | 2.5 | 1.5 | <0.01 |
| Arrest/ventricular fibrillation | 3.7 | 3.7 | 0.95 |
| Case complexity level | <0.01 | ||
| Level 1 | 75.2 | 79.6 | |
| Level 2 | 12.0 | 10.6 | |
| Level 3 | 7.6 | 6.3 | |
| Level 4 | 5.2 | 3.6 | |
| Intensive/cardiac care unit use | 65.7 | 73.8 | <0.01 |
| Admitted to hospital | 25.1 | 24.8 | 0.49 |
| Admitting physician | <0.01 | ||
| Cardiologist | 27.2 | 31.3 | |
| Internist | 33.6 | 37.3 | |
| General practitioner/other | 39.2 | 31.4 | |
| Neighbourhood income | <0.01 | ||
| Low | 47.4 | 41.0 | |
| Middle | 17.4 | 17.8 | |
| High | 30.2 | 35.3 | |
| Data missing | 5.1 | 6.0 |
Data presented as %
In both women and men, 90-day coronary catheterization rates increased over the study period (April 1, 1994, through December 31, 2002) (P<0.0001 for trend). In women, the 90-day coronary catheterization rates increased from 31.0% in 1994 to 49.4% in 2002; in men, this rate increased from 41.6% to 66.1% (Figure 1). Similar increasing trends in 90-day catheterization rates post-AMI were observed for both women and men over the study period. A segmented regression model with a common slope and one common inflection point for men and women was developed. The common inflection point was estimated to be September 2000 (95% CI April 2000 to February 2001). The common slope surrounding the inflection point indicated that the 90-day catheterization rates increased by 0.26% pre- and 2.19% postinflection point for every three-month period. The sex difference in 90-day coronary catheterization rates persisted throughout the nine-year study period (Figure 1).
Figure 1).
Three-month time trend of 90-day catheterization rates. The proportion of patients undergoing catheterization within 90 days of index admission in three-month intervals are represented by open circles and triangles for women and men, respectively. The line of best fit for each sex (thick solid line) was determined by segmented regression analysis. The inflection point is represented by the vertical solid line and the associated 95% CIs by the vertical dashed lines. AMI Acute myocardial infarction
The probability of undergoing catheterization within one year of AMI was 42.5% for women and 57.9% for men (Figure 2). After adjustment for baseline characteristics, women were still less likely to undergo catheterization, but this sex effect was modified by age and ICU/CCU use (P<0.0001 for interaction of sex and age; P<0.0001 for interaction of sex and ICU/CCU use). For patients who did not receive ICU/CCU care, women were consistently less likely to receive catheterization in all age groups; in contrast, in patients who received ICU/CCU care, sex differences only appeared in older patients (65 years of age or older) (Figure 3). There was no interaction between sex and AMI admission year.
Figure 2).
Cumulative probability of receiving catheterization after acute myocardial infarction within one year
Figure 3).
Adjusted sex ‘risk’ in receiving catheterization presented as HR (95% CI). CCU Cardiac care unit; ICU Intensive care unit. Age presented in years
Sex differences in coronary revascularization after cardiac catheterization following AMI
In the cardiac catheterization cohort, comprising 9233 patients, 2525 (27.3%) were women. Women were older and had significantly more DM, hypertension, PVD, CHF, CVD, COPD and liver disease than men. In contrast, women had fewer diseased coronary vessels and less hyperlipidemia (Table 2). Similar to the AMI cohort, more women than men came from a low-income neighbourhood (47.6% versus 40.7%).
TABLE 2.
Baseline characteristics of patients undergoing coronary revascularization by sex (n=9233)
| Characteristic | Women (n=2525) | Men (n=6708) | P |
|---|---|---|---|
| Age, years | <0.01 | ||
| <55 | 13.3 | 26.1 | |
| 55–64 | 20.9 | 27.4 | |
| 65–74 | 31.0 | 28.1 | |
| ≥75 | 34.8 | 18.4 | |
| Pulmonary disease | 12.7 | 9.8 | <0.01 |
| Renal disease | 4.4 | 3.9 | 0.26 |
| Hyperlipidemia | 53.1 | 56.2 | <0.01 |
| Hypertension | 61.9 | 48.5 | <0.01 |
| Heart failure | 22.0 | 14.2 | <0.01 |
| Cerebrovascular disease | 9.6 | 7.0 | <0.01 |
| Diabetes | 28.8 | 23.4 | <0.01 |
| Peripheral vascular disease | 10.1 | 7.1 | <0.01 |
| Liver disease | 5.5 | 4.1 | <0.01 |
| Cancer | 6.4 | 5.2 | 0.03 |
| Extent of diseased vessel | <0.01 | ||
| Less than 50% | 5.1 | 2.0 | |
| 1-vessel disease | 28.6 | 24.6 | |
| 2-vessel disease | 25.1 | 26.7 | |
| 3-vessel disease | 33.9 | 37.8 | |
| Left main disease | 7.4 | 9.0 | |
| Ejection fraction, % | 0.02 | ||
| <30 | 4.1 | 5.0 | |
| 30–50 | 28.2 | 30.2 | |
| >50 | 51.4 | 50.6 | |
| Data missing | 16.2 | 14.3 | |
| Neighbourhood income | <0.01 | ||
| Low | 47.6 | 40.7 | |
| Middle | 19.0 | 18.3 | |
| High | 29.9 | 35.9 | |
| Data missing | 3.5 | 5.1 |
Data presented as %
The probability of receiving revascularization within one year of the index catheterization following an AMI was 72.8% for women and 79.6% for men (log-rank P<0.0001). After adjusting for baseline characteristics, women were as likely to undergo revascularization as men (HR 0.96; 95% CI 0.91 to 1.02). While younger age was significantly associated with receiving revascularization, there was no interaction between sex and age. Also, there was no interaction between sex and catheterization year.
DISCUSSION
Coronary catheterization rates post-AMI increased significantly over the nine-year study period for both men and women. A steeper increase in 90-day catheterization rates post-AMI began in September 2000. Women were significantly less likely than men to receive coronary catheterization post-AMI and, after adjustment for baseline differences, this finding persisted in all age groups for patients who were not receiving ICU/CCU care. For patients who received ICU/CCU care, the sex difference appeared only in the older patients (65 years of age or older). Among patients who received coronary catheterization following AMI, women were as likely as men to undergo revascularization procedures (PCI or CABG).
Time trends in coronary catheterization rates post-AMI
Several studies have documented marked increases in the rates of coronary catheterization (3–6) and revascularization (3–6,11–13) following an AMI between 1975 and 2004. The first study (7) to report on the benefit of an early invasive approach following NSTEMI was published in August 1999 (Fragmin and Fast Revascularisation during InStability in Coronary artery disease [FRISC-II]). This was followed by two more publications in 2001 (Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction [TACTICS-TIMI]-18) (8) and 2002 (Randomized Intervention Trial of unstable Angina [RITA]-3) (9) that further supported this strategy. Importantly, in September 2000, the ACC/AHA guidelines for the management of patients with NSTEMI emphasized an early invasive approach (10). In Ontario, the inflection point for post-AMI angiography use predated publication of the FRISC-II trial by 11 months (14). In contrast, based on our BC data, the inflection point for post-AMI catheterization use was September 2000, which was 13 months following publication of the FRISC-II trial and coincident with the release of the 2000 ACC/AHA guidelines. It is possible that the acute rise in catheterizations in BC was, in part, a result of these publications; however, other potential factors, such as advances in technology, may also have had an important role. Of note, during the time-frame of the present study, the number of interventional cardiologists and cardiac catheterization laboratories remained stable.
Sex differences in coronary catheterization rates post-AMI
Earlier studies (1–3,15–18) from the United States and Europe support our findings of a significant sex difference in catheterization rates post-AMI. In Canada, studies from Quebec (1988 to 1995) (4), Ontario (1992 to 1996) (5) and Alberta (1994 to 1999) (6) all confirm lower catheterization rates in women than in men.
The studies mentioned above were conducted before the year 2000. Our study provides updated trends, confirming the continued finding of a sex difference in patients of all ages, although, only in the absence of ICU/CCU care. Interestingly, among patients who did receive ICU/CCU care, the sex difference remained only in patients 65 years of age or older. Perhaps the decision regarding whether to proceed to angiography is made earlier on, specifically in the process of deciding on referral to an acute care centre with an ICU/CCU.
Sex differences in coronary revascularization rates post-AMI
Earlier studies (1,3–6,16,17,19–23) found differing results regarding sex differences in revascularization rates, and some studies (1,4,6,19–22) have reported lower rates of revascularization in women than in men post-AMI. In our study, sex was significantly associated with receiving revascularization univariately, but this effect disappeared after the adjustment for age and extent of CAD. Our results are consistent with the results of the study by Ghali et al (23), in which the sex differences in rates of revascularization were fully explained after adjusting for baseline characteristics, mainly extent of CAD. This underlines the importance of proper and complete correction for baseline differences.
Possible explanations for the sex difference in procedure access
Several theories attempt to explain the sex differences observed in cardiac care. One observation is that women tend to present with more atypical AMI symptoms than men (24). Second, it remains controversial whether women derive the same benefit from an early invasive approach following AMI compared with men (25–27). Third, physician bias may also contribute to the sex differences observed. Schulman et al (28) demonstrated that sex independently affected whether a physician referred a patient with chest pain for coronary catheterization even after adjusting for baseline characteristics, symptoms and the physician’s estimation of the likelihood of CAD. Interestingly, the sex of the treating physician does not appear to contribute to the sex difference (29). Fourth, patient willingness to undergo invasive cardiac procedures may contribute to the sex difference. Women tend to rate their cardiac disease as less severe than men, even after controlling for other measures of disease severity (30). Finally, our results demonstrate that ICU/CCU care modified the sex effect on catheterization rates. Perhaps sex differences in catheterization are driven more by the decision to refer for ICU/CCU care in a tertiary centre than the decision to proceed with an invasive approach.
Limitations
Our study has several limitations inherent to administrative data. First, the International Statistical Classification of Diseases and Related Health Problems, Ninth Revision coding system cannot differentiate between STEMI and NSTEMI patients. Many of our conclusions regarding trends in catheterization rates with respect to the publication of major trials were in the NSTEMI population. While NSTEMI patients represent the bulk of acute coronary syndrome cases, we were unable to determine whether the trends we reported applied to STEMI or NSTEMI patients, or both. Second, while we did correct for factors such as age, comorbidities, physician and hospital characteristics, neighbourhood income level, admission year and case complexity, we were unable to correct for procedure appropriateness. Third, our reported rates of comorbidities tended to be lower than those quoted in clinical trials. While this under-reporting of comorbidities is a limitation in the study, it is unlikely that this phenomenon varied by sex.
CONCLUSIONS
Catheterization rates post-AMI increased significantly from 1994 through 2003. Women were significantly less likely to undergo catheterization even after adjustment for baseline characteristics; however, this sex effect was modified by age and ICU/CCU care. Specifically, among patients who did not receive ICU/CCU care, women were less likely than men to undergo catheterization in all age groups. For patients with ICU/CCU care, only older women (65 years of age or older) were less likely than men to receive coronary catheterization. Among patients who underwent coronary catheterization following their index AMI, women were as likely as men to undergo coronary revascularization within one year of catheterization.
Acknowledgments
The authors acknowledge the CSBCR, funded by the Provincial Health Services Authority, which provided data used in this study. The CSBCR is supported by cardiac surgeons, cardiologists, nurses and technologists at St Paul’s Hospital (Vancouver, BC), Vancouver Hospital and Health Sciences Centre (Vancouver), Royal Columbian Hospital (New Westminster, BC), Royal Jubilee Hospital (Victoria, BC) and Kelowna General Hospital (Kelowna, BC).
Footnotes
DISCLOSURES: Drs Humphries, Khan and Quan are Canadian Institutes of Health Research (CIHR) New Investigators. Dr Humphries is a Michael Smith Foundation Senior Scholar, Dr Quan is an Alberta Heritage Foundation Medical Research Population Investigator, and Dr Khan is a Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond (GENESIS) scholar.
FUNDING: The authors acknowledge the CIHR for directly funding this project, as well as the Canadian Cardiovascular Outcomes Team, and the Gender and Sex Differences in Cardiovascular Disease team, which are funded by the CIHR and the Heart and Stroke Foundation. The CIHR funded a larger project, of which the present study is a sub-analysis. The CIHR did not influence the design or conduct of the study; the management, interpretation and analysis of data; or the preparation, review and approval of the manuscript.
INSTITUTIONS WHERE WORK ORIGINATED: University of British Columbia, Vancouver, BC; Centre for Health Evaluation & Outcome Sciences, Vancouver; St Paul’s Hospital, Vancouver; the Department of Community Health Sciences and Centre for Health and Policy Studies, Calgary, Alberta; and the University of Calgary, Calgary.
REFERENCES
- 1.Anand SS, Xie CC, Mehta S, et al. Differences in the management and prognosis of women and men who suffer from acute coronary syndromes. J Am Coll Cardiol. 2005;46:1845–51. doi: 10.1016/j.jacc.2005.05.091. [DOI] [PubMed] [Google Scholar]
- 2.Rathore SS, Wang Y, Radford M, et al. Sex differences in cardiac catheterization after acute myocardial infarction: The role of procedure appropriateness. Ann Intern Med. 2002;137:487–93. doi: 10.7326/0003-4819-137-6-200209170-00008. [DOI] [PubMed] [Google Scholar]
- 3.Harrold LR, Esteban J, Lessard D, et al. Narrowing sex differences in procedure use for acute myocardial infarction. J Gen Intern Med. 2003;18:423–31. doi: 10.1046/j.1525-1497.2003.20929.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Pilote L, Lavoie F, Ho V, et al. Changes in the treatment and outcomes of acute myocardial infarction in Quebec, 1988–1995. CMAJ. 2000;163:31–6. [PMC free article] [PubMed] [Google Scholar]
- 5.Tu JV, Naylor CD, Austin P. Temporal changes in the outcomes of acute myocardial infarction in Ontario, 1992–1996. CMAJ. 1999;161:1257–61. [PMC free article] [PubMed] [Google Scholar]
- 6.Quan H, Cujec B, Jin Y, et al. Acute myocardial infarction in Alberta: Temporal changes in outcomes, 1994 to 1999. Can J Cardiol. 2004;20:213–9. [PubMed] [Google Scholar]
- 7.Fragmin and Fast Revascularisation during InStability in Coronary artery disease (FRISC-II) investigators Invasive compared with non-invasive treatment in unstable coronary artery disease. FRISC-II prospective randomised multicentre study. Lancet. 1999;354:708–15. [PubMed] [Google Scholar]
- 8.Cannon CP, Weintraub WS, Demopoulos LA, et al. for the TACTICS-Thrombolysis in Myocardial Infarction-18 investigators Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001;344:1879–87. doi: 10.1056/NEJM200106213442501. [DOI] [PubMed] [Google Scholar]
- 9.Fox KA, Poole-Wilson PA, Henderson RA, et al. Randomized Intervention Trial of unstable Angina investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: The British Heart Foundation RITA-3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet. 2002;360:743–51. doi: 10.1016/s0140-6736(02)09894-x. [DOI] [PubMed] [Google Scholar]
- 10.Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2000;36:971–1044. doi: 10.1016/s0735-1097(00)00889-5. [DOI] [PubMed] [Google Scholar]
- 11.Hochman HS, Tamis JE, Thompson TD, et al. Sex, clinical presentation, and outcomes in patients with acute coronary syndromes. GUSTO IIb investigators. N Engl J Med. 1999;341:226–32. doi: 10.1056/NEJM199907223410402. [DOI] [PubMed] [Google Scholar]
- 12.McGovern PG, Pankow JS, Shahar E, et al. Recent trends in acute coronary heart disease. N Engl J Med. 1996;334:884–90. doi: 10.1056/NEJM199604043341403. [DOI] [PubMed] [Google Scholar]
- 13.Heidenreich PA, McClellan M. Trends in treatment and outcomes for acute myocardial infarction: 1975–1995. Am J Med. 2001;110:165–74. doi: 10.1016/s0002-9343(00)00712-9. [DOI] [PubMed] [Google Scholar]
- 14.Singh SM, Austin PC, Chong A, et al. Coronary angiography following acute myocardial infarction in Ontario, Canada. Arch Intern Med. 2007;167:808–13. doi: 10.1001/archinte.167.8.808. [DOI] [PubMed] [Google Scholar]
- 15.Kilaru PK, Kelly RF, Calvin JE, Parrillo JE. Utilization of coronary angiography and revascularization after acute myocardial infarction in men and women risk stratified by the American College of Cardiology/American Heart Association guidelines. J Am Coll Cardiol. 2000;35:974–9. doi: 10.1016/s0735-1097(99)00641-5. [DOI] [PubMed] [Google Scholar]
- 16.Bertoni A, Bonds D, Lovato J, Goff DC, Brancati FL. Sex disparities in procedure use for acute myocardial infarction in the United States, 1995 to 2001. Am Heart J. 2004;147:1054–60. doi: 10.1016/j.ahj.2003.11.019. [DOI] [PubMed] [Google Scholar]
- 17.Woods KL, Ketley D, Agusti A, et al. Use of coronary angiography and revascularization procedures following acute myocardial infarction: A European perspective. Eur Heart J. 1998;19:1348–54. doi: 10.1053/euhj.1998.1027. [DOI] [PubMed] [Google Scholar]
- 18.Williams RI, Fraser AG, West RR. Sex differences in management of myocardial infarction: Not ‘sexism’ but a reflection of age at presentation. J Public Health. 2004;26:259–63. doi: 10.1093/pubmed/fdh159. [DOI] [PubMed] [Google Scholar]
- 19.Pilote L, Merret P, Karp I, et al. Cardiac procedures after an acute myocardial infarction across nine Canadian provinces. Can J Cardiol. 2004;20:491–500. [PubMed] [Google Scholar]
- 20.Milcent C, Dormont B, Durand-Zaleski I, et al. Sex differences in hospital mortality and use of percutaneous coronary intervention in acute myocardial infarction: Microsimulation analysis of the 1999 nationwide French hospitals database. Circulation. 2007;115:833–9. doi: 10.1161/CIRCULATIONAHA.106.664979. [DOI] [PubMed] [Google Scholar]
- 21.Fang J, Alderman MH. Sex differences of revascularization in patients with acute myocardial infarction. Am J Cardiol. 2006;97:1722–6. doi: 10.1016/j.amjcard.2006.01.032. [DOI] [PubMed] [Google Scholar]
- 22.Doyle F, De La Harpe D, McGee H, et al. Sex differences in the presentation and management of acute coronary syndromes: A national sample of 1365 admissions. Eur J Cardiovasc Prev Rehabil. 2005;12:376–9. doi: 10.1097/01.hjr.0000160725.82293.63. [DOI] [PubMed] [Google Scholar]
- 23.Ghali WA, Faris PD, Galbraith PD, et al. Sex differences in access to coronary revascularization after cardiac catheterization: Importance of detailed clinical data. Ann Intern Med. 2002;136:723–32. doi: 10.7326/0003-4819-136-10-200205210-00007. [DOI] [PubMed] [Google Scholar]
- 24.Milner KA, Funk M, Richards S, et al. Sex differences associated with coronary heart disease. Am J Cardiol. 1999;84:396–9. doi: 10.1016/s0002-9149(99)00322-7. [DOI] [PubMed] [Google Scholar]
- 25.Clayton TC, Pocock SJ, Henderson RA, et al. Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST elevation myocardial infarction? The impact of sex in the RITA 3 trial. Eur Heart J. 2004;25:1641. doi: 10.1016/j.ehj.2004.07.032. [DOI] [PubMed] [Google Scholar]
- 26.Lagerqvist B, Safstrom K, Stahle E, et al. Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? J Am Coll Cardiol. 2001;38:41–8. doi: 10.1016/s0735-1097(01)01308-0. [DOI] [PubMed] [Google Scholar]
- 27.Glaser R, Herrman HC, Murphy SA, et al. Benefit of an early invasive management strategy in women with acute coronary syndromes. JAMA. 2002;288:3124–9. doi: 10.1001/jama.288.24.3124. [DOI] [PubMed] [Google Scholar]
- 28.Schulman KA, Berlin JA, Harless W, et al. The effect of race and sex on physician’s recommendations for cardiac catheterization. N Engl J Med. 1999;340:618–26. doi: 10.1056/NEJM199902253400806. [DOI] [PubMed] [Google Scholar]
- 29.Rathore SS, Chen J, Wang Y, Radford MJ, Vaccarino V, Krumholz HM. Sex differences in cardiac catheterization: The role of physician sex. JAMA. 2001;286:2849–56. doi: 10.1001/jama.286.22.2849. [DOI] [PubMed] [Google Scholar]
- 30.Nau DP, Ellis JJ, Kline-Rogers EM, et al. Sex and perceived severity of cardiac disease: Evidence that women are “tougher”. Am J Med. 2005;118:1256–61. doi: 10.1016/j.amjmed.2005.08.006. [DOI] [PubMed] [Google Scholar]