Typical symptoms
Atypical symptoms
Chest pain
Pressure
Tightness
Squeezing
Sharp
Pleuritic
Burning
Aching
Soreness
Reproducible
Additional symptoms
Irradiation of pain to neck, jaw, shoulders, arms, and back
Dyspnea
Nausea and vomit
Profused diaphoresis
Unusual shortness of breath
Neck, jaw, arm, and/or shoulder pain
Back pain
Flu-like symptoms
Dizziness
Anxiety
Generalized weakness
Indigestion symptoms
Palpitations
Multiple studies have shown that women with STEMI are less likely to be treated with guideline-directed medical therapies, less likely to undergo cardiac catheterization, and less likely to receive timely reperfusion [14–18].
A recently published analysis of the VIRGO study showed that young women presenting with STEMI are less likely to receive reperfusion and more prone to experience delays in receiving reperfusion as compared with similarly aged men [19]. Furthermore, women with >50 % coronary stenosis documented at cardiac catheterization were less likely to receive revascularization as compared with men. After adjustment for confounders, female gender persisted as an independent factor in the delay of reperfusion therapy. In addition, a differential access to treatment has been observed, with young women being less likely to receive revascularization than young men with subsequently higher in-hospital mortality as well as longer in-hospital stay [20].
Notably, previous data have indicated that when women are given effective reperfusion therapy with primary percutaneous coronary intervention (PCI), they experience the same risk of death as men [21]. A prompt diagnosis of STEMI and an adequate strategy to provide prompt myocardial reperfusion is crucial for women as for men. Therefore, it is important to maintain a high degree of awareness for STEMI in women with potential symptoms of ischemia. It must be underscored that delays in the timely implementation of reperfusion strategies represent key issues in the management of STEMI, since the greatest benefit achieved with reperfusion occurs within the first 2–3 h after symptoms onset. Optimal management of patients with STEMI – irrespective of sex – including pre- and in-hospital pathways and reperfusion strategies within 12 h of first medical contact with ideal time interval for interventions as recommended by the current European guidelines are depicted in Fig. 5.1 [22].
Fig. 5.1
Optimal management and reperfusion strategies in patients with STEMI within 12 h of first medical contact with ideal time interval for interventions. DI-DO door-in to door-out time, DTB door-to-balloon time, EMS emergency medical service, FMC first medical contact, FMCTB first-medical-contact-to-balloon time, PCI percutaneous coronary intervention, STEMI ST-segment elevation myocardial infarction (Reproduced with permission from [22])
5.4 Reperfusion in Women with STEMI
A prompt restoration of coronary flow and myocardial tissue perfusion has been consistently shown to improve survival in women and men with STEMI [22]. According to the European and American guidelines, for women and men with STEMI within 12 h of symptom onset and with persistent electrocardiographic changes (ECG), early mechanical (PCI) or pharmacological reperfusion should be performed as early as possible [23]. There is general agreement that reperfusion strategies should be implemented also among patients with symptoms onset >12 h in case of clinical and/or electrocardiographic evidence of ongoing ischemia. Overall, as reflected by current guidelines, available evidence consistently indicates that patients with STEMI should be timely treated with reperfusion therapy irrespective of sex.
5.5 Mechanical Reperfusion: Primary PCI in Women
Primary PCI is the preferred reperfusion strategy in patients with STEMI, provided that it can be performed expeditiously by experienced operators [4, 22]. During the last 15 years, primary PCI has become established as the dominant reperfusion therapy across the great majority of the European countries.
Since female patients represent a group at high risk of complications from pharmacological reperfusion with fibrinolysis, it is not unsurprising that they benefit the most from primary PCI – mainly due to the near elimination of the risk of major bleeding. In a pooled analysis of 22 randomized trials, women with STEMI had a lower risk of mortality with primary PCI as compared to fibrinolysis, irrespective of whether they presented within the first 2 h of symptom onset (7.7 % vs. 9.6 %) or >2-h delay (8.5 % vs. 14.4 %) [24]. It must be underscored that primary PCI resulted as an independent predictor of survival in women. The favorable treatment effect of primary PCI over fibrinolysis in women with STEMI was corroborated by a substudy of the GUSTO IIB, with primary PCI preventing 56 deaths per 1000 treated women as compared with 42 deaths per 1000 treated men [25].
However, despite the improvement in clinical outcomes among women treated with primary PCI, a meta-analysis of observational studies found that women have a higher risk of in-hospital mortality as compared with men after adjustment for baseline risk differences (RR 1.48; 95 % CI 1.07–2.05) [26]. Moreover, while primary PCI has eliminated the risk of intracranial bleeding as compared to fibrinolysis, female patients remain at higher risk of bleeding events and vascular complications as compared to male patients [27]. These findings indicate the need for a further optimization in the treatment of women with STEMI.
5.5.1 Multivessel Treatment Strategies in Women with STEMI
The infarct-related artery should be systematically treated during the initial intervention. This strategy is valid for both men and women with the aim of a rapid and stable reperfusion. In case of multivessel disease, evidence supporting complete revascularization with PCI of non-infarct-related lesions is a matter of debate [28]. The presence of extensive multivessel CAD has been associated with a reduced success in reperfusion and impaired clinical outcomes following primary PCI, supporting the need for complete revascularization in women and men with STEMI. Along this line, in the preventative angioplasty in acute myocardial infarction (PRAMI) trial, 465 patients with STEMI and multivessel CAD were randomly allocated to preventive PCI in non-infarct-related coronary arteries with stenosis ≥50 % or PCI limited to the infarct artery [29]. During a mean follow-up of 23 months, preventive PCI was associated with a reduced risk of the composite of death, myocardial infarction, or refractory angina as compared with PCI limited to the infarct-related artery (HR 0.35; 95 % CI 0.21–0.58; p < 0.001). A stratified analysis of the primary endpoint showed that the treatment effect of preventive PCI with respect to the primary endpoint was consistent among women (HR 0.24, 95 % CI 0.08–0.73) and men (HR 0.39, 95 % CI 0.22–0.68) with no evidence of statistical interaction [29]. With respect to timing, staged PCI in STEMI patients with multivessel disease and no hemodynamic compromise has been identified as an independent predictor of survival. Moreover, a higher risk of ischemic events has been associated with simultaneous PCI of multiple vessels (in addition to the culprit vessel) at the time of STEMI as compared with staged revascularization of STEMI patients with multivessel disease. Based on the available evidence, current guidelines recommend to consider multivessel PCI in STEMI patients with cardiogenic shock in the presence of multiple, critical stenoses or highly unstable lesions, and if there is persistent ischemia after PCI on the culprit lesion [4, 22].
5.5.2 Stent Selection
Stenting is the default strategy over balloon angioplasty in women and men with STEMI treated with primary PCI, since it has been shown to reduce the risk of abrupt vessel closure, reinfarction, and repeat revascularization [30, 31]. Although early-generation drug-eluting stents (DES) have not been associated with an increased risk of death, myocardial infarction, or stent thrombosis during long-term follow-up [32], there have been concerns of an increased risk of very late stent thrombosis owing to delayed arterial healing of stents implanted into unstable lesions underlying STEMI [33, 34]. Two randomized trials in STEMI patients undergoing primary PCI directly compared new-generation DES with bare-metal stents (BMS). In the EXAMINATION trial, everolimus-eluting stent implantation in STEMI patients resulted into lower risks of target lesion revascularization (2.1 % vs. 5.0 %, p = 0.003) and definite stent thrombosis (0.5 % vs. 1.9 %, p = 0.02) as compared to BMS [35]. Similarly, the COMFORTABLE AMI trial reported a lower risk of the composite primary endpoint of cardiac death, target-vessel myocardial infarction, and target lesion revascularization (4.3 % vs. 8.7 %; HR 0.49, 95 % CI 0.30–0.80, p = 0.004) as well as a lower risk of target-vessel myocardial infarction (0.5 % vs. 2.7 %; HR 0.20, 95 % CI 0.06–0.69, p = 0.01) and a trend towards a lower risk of definite stent thrombosis (0.9 % vs. 2.1 %; HR 0.42, 95 % CI 0.15–1.19, p = 0.10) in patients assigned to treatment with biolimus-eluting stents with a biodegradable polymer compared with BMS [36]. Results were maintained throughout longer-term follow-up and a pooled analysis of both trials confirmed a lower risk of stent thrombosis and reinfarction with DES compared with BMS [37]. As a matter of fact, the improved safety and efficacy of new-generation DES over early-generation DES as well as BMS has been shown in a pooled analysis of 26 randomized trials including 11,557 women with no evidence of interaction between treatment effect and acute presentation at baseline (Fig. 5.2) [38]. Taken together, these findings suggest that new-generation DES are more effective and potentially safer than BMS as well as early-generation DES during primary PCI in women and men with STEMI.
Fig. 5.2
Progressive improvements in safety and efficacy associated with coronary stent iterations in women. DES drug-eluting stents, BMS bare-metal stents (With permission from [38])
5.5.3 Arterial Access Site Selection
Access site selection may be of particular relevance in women with STEMI. Radial strategy has been shown to reduce the incidence of acute bleeding events, particularly in acute coronary syndromes, and was associated with lower mortality in the subset of STEMI patients enrolled in the RIVAL trial [39–41]. However, the beneficial effect of radial over femoral access appears to be dependent upon the radial expertise of operators [42]. In a sex-based subanalysis of the RIVAL trial, female patients resulted to have a higher risk of vascular access site complications compared with male patients, and radial access emerged as an effective method to reduce these complications [43]. In the recently published MATRIX trial, 8,404 patients with acute coronary syndrome (with or without ST-segment elevation) were randomly allocated to radial (4197) or femoral (4207) access for coronary angiography and PCI [44]. At 30 days, radial access resulted in a reduced risk of the co-primary endpoints of major adverse cardiac events (MACE: death, myocardial infarction, or stroke; RR 0.85, 95 % CI 0.74–0.99; p = 0.0307) and net adverse clinical events (NACE: major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding; RR 0.83, 95 % CI 0.73–0.96; p = 0.0092). A stratified analysis of the co-primary endpoints showed a more pronounced treatment effect in women (MACE: RR 0 · 73, 95 % CI 0 · 56–0 · 95; NACE: RR 0 · 72, 95 % CI 0 · 56–0 · 93) than men (MACE: RR 0 · 92, 95 % CI 0 · 77–1 · 09; NACE: RR 0 · 89 95 % CI 0 · 76–1 · 05) without formal statistical interaction. Overall, available evidence consistently indicate that radial access may improve the safety and efficacy outcomes of primary PCI in both sexes and might effectively reduce the gender difference in prognosis.
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