STElevation Myocardial Infarction Thrombolytic Therapy

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While aggressive reperfusion therapy with pharmacologic agents has been shown to reduce in-hospital mortality by as much as 25-30%, women are more likely to have a contraindication to thrombolysis and, therefore, not receive thrombolytic therapy (122). This observation was confirmed in a series of1059 patients who presented with an acute myocardial infarction, which revealed that women were less likely to receive throm-bolytic agents than men (126). Moreover, it has been shown that only 55% of eligible women compared with 78% of eligible men receive tissue plasminogen activator. In contrast to these observations, a recent retrospective review of women age 50 yr or younger, who presented with an acute myocardial infarction, determined that 94% of women met eligibility criteria for thrombolytic agents, and 91% of these women were treated with drug. The most common reasons for withholding thrombolytic agents were nondiagnostic electrocardiogram and late presentation (> 12 h after symptom onset) to the emergency department (127).

Once administered, thrombolytic agents have similar efficacy in women and men as demonstrated by 90-min infarct-related artery patency rates (39 vs 38%), reocclusion rates (8.7 vs 5.1%), and left ventricular ejection fraction and regional ventricular function, which has been reported to be similar in women and men, although women have more recurrent ischemia (21.4 vs 17.0%). Despite these similarities, the 30-d mortality rate was 13.1% in women vs 4.8% in men (p < 0.0001), and after adjustment for other clinical and angiographic variables, gender remained an independent predictor of 30-d mortality (123).

In a meta-analysis of the Fibrinolytic Therapy Trialists' Collaboration Group, which included all randomized clinical trials that compared thrombolytic agents with a placebo or control group, the absolute benefit of thrombolytic therapy with regard to 35-d mortality was 2.2% in female patients compared to 1.9% in male patients. In addition, female gender and low body weight were identified as independent risk factors for cerebrovascular and hemorrhagic complications associated with thrombolytic therapy (128). Furthermore, the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) study revealed a trend toward lower total stroke rate and 30-d mortality in female patients over 75 yr of age treated with tenecteplase than in those treated with alteplase. These observations suggest that female patients, especially over 75 yr of age, will probably benefit greatly from a thrombolytic agent with a weight-based dosing regimen (128).

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial database evaluated 41,021 patients with suspected acute myocardial infarction and demonstrated a significant gender difference with respect to the unadjusted 1-yr mortality rate for the initial GUSTO-I population and 30-d survivors. For the initial population, when adjusted for age, women had a significantly worse outcome than men (odds ratio = 1.4, 95%, CI: 1.3-1.5, p < 0.001). Interestingly, for the 30-d survivors, adjustment based on age alone explained the 1-yr mortality difference (risk ratio = 0.96, 95% CI: 0.85-1.07, p = 0.441) between men and women (129).

Treatment of young women with thrombolytic therapy was previously thought to be problematic owing to the increased risk of hemorrhage associated with active menstruation. Although studies have suggested that there may be an increase in the risk of moderate bleeding in menstruating patients treated with thrombolytic agents, the GUSTO-I study revealed that the mortality reduction associated with thrombolytic therapy for acute myocardial infarction should not be withheld because of active menstruation (130).

Primary Angioplasty

Percutaneous revascularization strategies to restore coronary artery patency during acute myocardial infarction in the absence of prior thrombolytic therapy, or primary angioplasty, results in a higher infarct-related coronary artery patency rate (131), smaller enzymatic infarct size, increased preservation of left ventricular function, and improved clinical outcome compared to thrombolytic therapy (131-133). A pooled analysis of early clinical trials of primary angioplasty revealed a 44% mortality reduction during hospitalization (OR 0.56, CI: 0.53-0.94) and a 9% mortality reduction at 1 yr (134). Yet, despite the observed survival benefit, women are more likely to refuse catheterization as a therapeutic modality for acute myocardial infarction. Of the 2.4% of patients who reported that they were likely to refuse primary angioplasty, a significant proportion were older women with a history of prior myocardial infarction (135).

Women who present with acute myocardial infarction who undergo primary angio-plasty comprise a higher risk patient population compared to men. This was demonstrated in The Primary Angioplasty in Myocardial Infarction (PAMI) trial, which compared primary angioplasty with tissue-type plasminogen activator, and revealed that women were older (65.7 vs 57.7 yr,p < 0.0001) and had a higher incidence of diabetes (19 vs 10%, p < 0.03), hypertension (54 vs 39%, p < 0.005), and a history of congestive heart failure (5 vs 0%, p = 0.002) compared to men. Women were more likely to present later after symptom onset than their male counterparts (229 vs 174 min, p = 0.0004), and in-hospital mortality for women was 3.3-fold higher than men (9.3 vs 2.8%, p = 0.0005) (131,136). In the subset of women who were assigned to the angiography arm of the study, women were less likely than men to undergo percutaneous revascularization procedures owing to a higher prevalence of surgical disease or the presence of a noncritical stenosis. In women that did undergo angioplasty, the in-hospital mortality rate was similar to men (4.0 vs 2.1%), and percutaneous revascularization and younger age were independent predictors of in-hospital survival in women. Importantly, cerebrovascular hemorrhage occurred in 5.3% of women treated with a thrombolytic agent compared with 0.7% men (p = 0.037), while there was no increase in hemorrhagic events, regardless of gender, with primary angioplasty. These observations suggest that primary angioplasty improves survival in women, such that it is comparable to men, and reduces the risk of hemorrhagic stroke that is associated with thrombolytic therapy (136,137).

Women with acute myocardial infarction tend to have a worse prognosis then men because they present much later after symptom onset. To examine the influence of late presentation on the efficacy of primary angioplasty, a study of 496 patients with acute myocardial infarction who underwent primary angioplasty specifically assessed outcome in patients who were treated between 6 and 24 h. Patients who presented late were more often female, underwent primary angioplasty procedures with a lower success rate compared to patients with early presentation, resulting in a greater deterioration of left ventricular function. Patients who did undergo a successful revascularization procedure were more likely to have reocclusion of the infarct-related artery, repeat myocardial infarction, and a significantly higher mortality rate at 6 mo (138).

As coronary stents are increasingly utilized in primary revascularization procedures, the Stent-PAMI trial compared coronary stent implantation with balloon angioplasty for the treatment of acute myocardial infarction. At 6-mo follow-up, the combined primary end point of death, reinfarction, cerebrovascular accident, or target-vessel revascular-ization for ischemia, was reached by fewer patients in the stent group than in the angioplasty group (12.6 vs 20.1%, p < 0.01) (139). Women in this trial were older (66 ± 12 vs 58 ± 12 yr, p < 0.0001), had a higher incidence of hypertension, hypercholesterolemia, diabetes, and smaller size infarct-related artery at angiography compared to men. Even though TIMI grade 3 flow was restored in a greater percentage of women than men (94 vs 90.0%, p = 0.07), by 6 mo, women had increased rates of death (7.9 vs 2.0%, p = 0.0002), reinfarction (6.4 vs 2.7%, p = 0.01), and stroke (2.0 vs 0.3%, p = 0.01), with similar rates of late target vessel revascularization. These data have been confirmed in other studies (140) and demonstrate that women undergoing percutaneous revascularization in the stent era remain at high risk for adverse events (142).

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