Acute Coronary Syndromes

Abstract

12. Acute Coronary SyndromesDoes Sex Matter?Judith S. Hochman, MD Jacqueline E. Tamis-Holland, MD I N 1960, THE AMERICAN HEART ASSOCIATION (AHA) SPONsored a conference in Portland, Ore about women and cardiovascular disease (CVD) entitled "How I Can Help My Husband Cope With Heart Disease." Today, recognizing that cardiovascular disease is the leading cause of death for women older than 50 years, the AHA now routinely holds conferences about heart disease in women, and the National Heart, Lung, and Blood Institute and the National Institutes of Health Office of Research on Women's Health devote substantial attention to this area. Do women and men respond to cardiovascular therapies in the same way? For the most part, yes. However, biological differences, down to the cellular level, might account for different therapeutic effects and adverse responses.1 For example, women are at greater risk from drugs that prolong the QT interval, including antiarrhythmics, antibiotics, and antihistamines.2 Similarly, in patients with congestive heart failure, a recent study suggested that digitalis use was associated with excess risk of death in women but not in men. 3 In this issue of THE JOURNAL, Glaser and colleagues 4 report an important observation from the TACTICS-TIMI 18 (Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) study-that an early invasive strategy in women with non-ST-segment elevation acute coronary syndrome (ACS) results in similar benefits to men so treated. This observation stands in contrast to the findings of 2 previously reported studies testing an invasive strategy for non-ST-segment elevation ACS, the FRISC II (Fragmin and Revascularization during Instability in Coronary artery disease II) 5 and RITA-3 (Randomized Intervention Trial of unstable Angina 3) studies. 6 These studies reported benefit for men and a suggestion of harm for women. Why the different results?In TACTICS-TIMI 18, 2220 patients with non-STsegment elevation ACS, including myocardial infarction (MI) and unstable angina, were randomly assigned to receive either an invasive strategy (routine coronary angiography, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) or a conservative strategy (medical therapy, with revascularization reserved for patients with spontaneous or inducible ischemia). One third of the participants were women; they were older than the men and had higher rates of hypertension and diabetes, and lower rates of prior MI and revascularization. Women had higher rates of no significant coronary artery stenoses compared with men, and less often had elevated levels of cardiac troponin T. These findings are consistent with the results from other trials and registries of patients with ACS. Earlier studies have also reported more nonspecific electrocardiographic changes and atypical symptoms in women with ACS. 7,8 Women more often have coronary spasm with minimal coronary stenoses, as well as card...

Gender Bias in Cardiovascular Testing Persists after Adjustment for Presenting Characteristics and Cardiac Risk

“…36,38 In both our study and other studies, 8,30,38 women who received a cardiac catheterization were less likely than male counterparts to have CAD. Others have reported that women are 30%-50% less likely to have CAD, 9,10,31 which is consistent with our finding that 57% of women and 73% of men who received cardiac catheterization were found to have CAD. Anticipating this finding, we adjusted for cardiac risk to determine if it might account for the increased likelihood of men receiving more diagnostic testing.…”

Percutaneous Coronary Intervention and Adjunctive Pharmacotherapy in Women

“…71,74 Potential explanations for the differences between TACTICS-TIMI 18 versus RITA-3 and FRISC-II include the delayed timing of intervention in the invasive arm of FRISC-II, an apparent low rate of events for women in the conservative strategy in the latter 2 studies (suggesting a lower-risk population), lack of routine use of GP IIb/IIIa antagonists, and greater use of coronary artery bypass graft surgery (CABG) with an associated high risk of death for women in FRISC-II (9.9% in women versus 1.2% in men, PϽ0.001). 75 In summary, women with UA/ NSTEMI and high-risk features benefit from an invasive strategy with early intervention (within 48 hours) and adjunctive GP IIb/IIIa antagonist use. 69 …”

Application of Current Guidelines to the Management of Unstable Angina and Non-ST-Elevation Myocardial Infarction

“…The benefit of GP IIb/IIIa administration in women with elevated troponin concentrations were similar to those in men. 59 The relation between gender and the benefit of an early invasive management strategy has been examined in four studies. A significant interaction between gender and the treatment effect of an invasive strategy was observed in FRISC II 51 and RITA 3, 53 with absence of benefit in women.…”

“…Yet in TACTICS-TIMI 18 16 and in a prospective cohort study, 60 no difference in response was observed. Whereas the explanation for these differences is not entirely clear, 59 it is inappropriate to withhold an invasive strategy from women at high or intermediate risk who have obstructed coronary arteries that are suitable for revascularization.…”