Gender-specific issues in the management of patients with acute coronary syndrome
2008; Lippincott Williams & Wilkins; Volume: 121; Issue: 23 Linguagem: Inglês
10.1097/00029330-200812010-00001
ISSN2542-5641
Autores Tópico(s)Antiplatelet Therapy and Cardiovascular Diseases
ResumoAcute coronary syndrome (ACS) represents a continuum of acute myocardial ischemia including non-ST-elevation myocardial infarction and unstable angina, synonymous with non-ST-elevation ACS (NSTE-ACS), and ST-elevation myocardial infarction (STEMI). A large body of clinical evidence has demonstrated the great impact of gender differences on the treatment of ACS and clinical outcomes of these patients.1-5 In general, women develop coronary artery disease about 10 years later than men though the reasons for this remain unclear. The prevalence of obstructive coronary disease is lower in women across all age groups than that in men, but increases dramatically in women after the age of 50 years.6,7 The correlation of symptoms with coronary disease is less accurate and less precise in women than that in men, and risk assessment of coronary artery disease in women is usually more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. Compared with men, women with ACS at a high risk undergo less coronary angiography,2 and among patients undergoing urgent coronary angiography for ACS, women have a higher prevalence of non-obstructive coronary arteries, leading to diagnostic uncertainty and delayed treatment.8 These patients receive less frequently coronary revascularization therapy, and have increased rates of refractory ischemia and re-hospitalization.2 In approximately 60% of cases, the initial presentation of ischemic heart disease in women is acute myocardial infarction or sudden cardiac death,9 resulting mainly from plaque rupture (which contains a large necrotic core and disrupted fibrous cap infiltrated by macrophages and lymphocytes) in older women or from plaque erosion and intima exposure in their younger counterparts. Nevertheless, all these changes in atherosclerotic plaques lead to a great tendency toward thrombus formation. In the setting of acute or chronic obstructive coronary disease, women have an overall prognosis worse than men,1-5,9 driven by the acuity of presentation and the degree of co-morbidity.10 In the management of patients with NSTE-ACS, reliance on symptoms, electrocardiographic changes, cardiac biomarkers, and status of left ventricular function and coronary disease for risk stratification is crucial because of the differences in presentation between men and women. In a TACTICS-TIMI 18 sub-study, a different pattern of presenting biomarkers was revealed. Men are more likely to have elevated levels of creatine kinase-MB and troponins, whereas women are more likely to have elevated levels of C-reactive protein and brain natriuretic peptide. This suggests that a broader, multi-marker approach may aid initial risk assessment of NSTE-ACS, especially in women.11 Likewise, significant disparities exist in gender regarding practical treatment strategy for patients with NSTE-ACS. The analysis of the CRUSADE data showed that the time of electro-cardiography was longer for women than for men, women were less likely cared by a cardiologist, and invasive diagnostic measures and treatments were less frequently used in women. Although women with NSTE-ACS are at a higher risk for unadjusted adverse clinical outcomes during hospitalization, they less frequently received guidelines-recommended therapy than men. These patterns of relative under-treatment in women were similar whether older, more established or newer therapies are considered.3 Moreover, women who undergo myocardial revascularization may fare worse than men, in that women tend to be older, have more cardiac risk factors, and smaller coronary arteries that may not be amendable to percutaneous coronary intervention (PCI).1 The RITA-3 gender-specific subgroup analysis showed that women at a moderate risk had no significant reduction in the composite of death and myocardial infarction at one year with early PCI treatment compared with men,12 emphasizing the need to make our decisions of early coronary intervention according to the presence of high-risk features in the management of NSTE-ACS patients. The gender differences in risk factors for STEMI, the use of therapeutic modalities, and clinical outcomes of patients have been extensively investigated. The INTERHEART global case-control study showed that women experienced their first acute STEMI on average 9 years later than men, and men were significantly more likely to suffer a myocardial infarction prior to 60 years of age than women. The difference in age of the first myocardial infarction is largely explained by the higher risk factor levels at younger ages in men compared with women.13 For example, if younger men reduced their smoking and lipid to the levels seen in younger women, they would live 9-10 years longer before their first myocardial infarction.14 Hypertension, diabetes, psychosocial factors, lack of physical activity, and lack of alcohol consumption were more potent risk factors for acute STEMI in women than those in men.13 More than 30% of patients with acute STEMI could not survive to hospitalization, and women were more likely to die before hospitalization than men.15 Moreover, the proportion of unrecognized myocardial infarction in women (54%) was higher than that in men (33%).16 In general, women with acute STEMI have a higher crude hospital mortality rate than men. This difference has partly been ascribed to their older age, higher prevalence of co-morbidities, and less aggressive hospital management in women.17-19 However, age-adjusted hospital mortality was higher for women and was associated with a lower rate of PCI. Women would benefit from more frequent use of PCI, although the procedure appears to be less protective in women than that in men.19 Younger women presenting acute STEMI are also at a particularly high risk of death, as recently reported in the National Registry of Myocardial Infarction-2 database, in part due to co-morbidity, infarct severity, and medical management differences. There are also discrepancies in the rate of therapeutic interventions between two genders, as men have substantially higher rates of thrombolysis and coronary angiography compared with women.4 Myocardial reperfusion with primary PCI has become the first treatment of choice for the management of acute STEMI.20-23 The results of CADILLAC trial indicate that the higher mortality rate in women compared with men after primary PCI for acute STEMI may be explained by differences in body size and clinical risk factors, although female gender remains an important independent determinant of overall adverse outcomes. In women, the addition of platelet glycoprotein IIb/IIIa receptor inhibitor reduced the 30-day target vessel revascularization rate without increasing bleeding risk, and primary PCI with bare-metal stents reduced 1-year major adverse cardiac events compared with single balloon dilation.24 Previous studies in the bare-metal stent era have shown gender differences in PCI with more adverse events observed in women.2,3,12,24 So far, there has been a paucity of evidence regarding the gender effects on outcomes after PCI with drug-eluting stent implantation. Morice et al25 compared the mid-term outcome between men and women treated with PCI in the ARTS II trial. They found that women of old age and less smoking had more diabetes, hypertension, obesity, worse angina, and better ejection fraction than men, but angiographic and procedural characteristics were similar between the two genders. There were no gender-specific differences in terms of in-hospital outcome and incidence of major adverse cardiac and cerebrovascular events at one-year follow-up. In this issue of the Chinese Medical Journal, Liu et al26 retrospectively analyzed clinical, angiographic and follow-up data of 259 patients with acute STEMI. Primary PCI was performed within 12 hours of symptoms and drug-eluting stents were applied to about 80% of patients. Similarly, they found that hypertension, diabetes, and 3-vessel disease were more common but cigarette smoking was less often in female than that in male patients. After PCI, both genders had high infarct-related artery patency and procedural success rates as well as favorable in-hospital outcomes. However, women experienced more major adverse cardiac events during follow-up (average 16 months). These “real-world” observations suggest that female patients still have worse long-term prognosis even treated with primary PCI and drug-eluting stent implantation. It is still unknown whether such gender difference reflects differential risk profiles of the female patients, the time between symptom-onset and intervention, the adjunctive medical therapies, or as yet unidentified factors. To further delineate the importance of gender difference in the interventional management of patients with acute STEMI in the drug-eluting stent era, clinical trials with a large number of patients are warranted. Because women make up at least 50% of our patient population, we must be vigilant and continue to search for explanation for these gender disparities and new treatment options.27
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