Women are frequently reported to have increased morbidity after presentation with acute coronary syndromes and myocardial infarction; however, whether a greater thrombotic tendency contributes to gender differences in clinical outcomes of urgent percutaneous coronary intervention is unknown. Intraprocedural Thrombotic Events (IPTEs) are defined as new or increasing thrombus, abrupt vessel closure, no reflow or slow reflow, or distal embolization at any time during percutaneous coronary intervention. IPTEs were evaluated in this pooled analysis of 6,591 patients with stent implantation and blinded quantitative coronary angiography (QCA) analysis, from the ACUITY and HORIZONS-AMI trials. We compared major adverse cardiac events (MACE) at in-hospital, 30-day, and 1-year follow-up and major bleeding at 30 days according to gender and the presence or absence of IPTE. IPTE was identified in 507 patients (7.7%), with 119 of 1,744 (6.8%) occurring in women and 388 of 4,847 (8.0%) in men (p = 0.12). IPTE, but not gender, was independently associated with MACE at in-hospital and 30-day follow-up. At 1-year follow-up, the adjusted hazard of MACE was higher in women and in patients with IPTE; however, the risk of MACE associated with IPTE was similar among women and men. There was no significant interaction between IPTE and gender for 1-year MACE or 30-day bleeding. IPTE predicted major bleeding only in women. In conclusion, in acute coronary syndromes, women have increased risk of adverse outcome at 1 year. IPTEs are common, occur at similar frequency, and are associated with similar degree of increased MACE in both genders at short- and long-term follow-up. Higher thrombotic propensity does not offer a mechanistic explanation for the worse outcomes noted in women.
Women have increased platelet reactivity compared with men despite dual antiplatelet therapy. Multiple studies have shown that women fare worse than men after myocardial infarction (MI), especially during the early (in-hospital and subacute) post-MI phase. The underlying causes of a higher post-MI mortality in women are controversial, as several reports conclude that gender differences are explained by age, later presentation, and more severe baseline comorbidities in women. Therefore, it is of interest to link the higher platelet reactivity with an elevated thrombotic tendency as a plausible causal explanation for the increased rates of major adverse cardiac events (MACE) in women after MI. Intraprocedural thrombotic events (IPTEs) have recently emerged as a cardiovascular risk marker and are strongly associated with adverse ischemic and bleeding outcomes in patients undergoing percutaneous coronary intervention (PCI). An IPTE is a composite of new or worsened thrombus, abrupt vessel closure, distal embolization, and no reflow or slow reflow with thrombus being a major contributor to this composite. The aims of the present study were to compare the incidence of IPTEs in women and men and to investigate whether IPTEs account for the observed gender differences in outcomes after acute coronary syndrome (ACS).
Methods
We compared MACE according to gender and the presence or absence of IPTE in a pooled analysis of the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trials. The study design, protocol, and primary results of the HORIZONS-AMI and ACUITY trials have been previously described in detail.
In brief, the HORIZONS-AMI trial was a large-scale, prospective, dual-arm, open-label, multicenter, randomized study designed to determine the safety and efficacy of the direct thrombin inhibitor bivalirudin compared with unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPIs), and the paclitaxel-eluting TAXUS stent (Boston Scientific, Natick, Massachusetts) compared with an otherwise identical bare-metal EXPRESS stent (Boston Scientific) in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary PCI. A total of 3,602 patients undergoing primary PCI were enrolled internationally at 123 medical centers and randomized in a 1:1 ratio before coronary arteriography to UFH with a GPI or bivalirudin, with the provisional use of GPIs for strictly defined thrombotic conditions in the cardiac catheterization laboratory. Aspirin was administered indefinitely, and clopidogrel was prescribed for ≥6 months (≥1 year was recommended). Of the 3,602 patients enrolled in HORIZONS-AMI, 3,280 patients had stents implanted during primary PCI, and for 3,163 of those patients films were available and evaluable for quantitative coronary angiography (QCA) analysis.
In ACUITY, 13,819 patients presenting with non–ST-elevation ACS were prospectively randomized to 1 of 3 antithrombotic regimens, UHF plus a GPI, bivalirudin plus a GPI, or bivalirudin alone. Angiography was performed in all patients within 72 hours followed by triage to PCI, coronary artery bypass graft surgery (CABG), or medical therapy at the discretion of the physician. Aspirin loading was done before catheterization, whereas clopidogrel was given to all patients either before catheterization or within 2 hours after PCI. Aspirin was continued indefinitely, and clopidogrel was continued for 1 year after hospital discharge. A prespecified angiographic ACUITY substudy was undertaken in 6,921 consecutive patients from US centers. From this group, PCI was performed in 3,428 patients.
Consequently, the present study was a pooled analysis in 6,591 patients with 3,163 STEMI patients with available QCA originating from the HORIZONS-AMI trial and 3,428 patients with non-ST segment elevation with available QCA originating from the ACUITY trial ( Figure 1 ).
