The principal clinical findings from this large cohort study can be summarized as follows: (1) female patients with TVD who underwent revascularization had more unfavorable baseline risk profiles, including hypertension, diabetes mellitus, dyslipidemia, CKD, prior cerebrovascular disease and LMT disease. (2) there were no sex-related differences in the long-term outcome after coronary revascularization among patient with TVD. (3) hypertension, diabetes mellitus, atrial fibrillation, LMT involvement and LVEF ≤ 40% were independently associated with a higher MACCE rate in these patients. Female gender was not an independent predictor of MACCE.
Three-vessel disease is a severe form of CAD associated with a high risk of adverse outcomes. Evidence shows that in women with TVD, revascularization was superior to medical therapy for the primary composite endpoint of overall mortality, unstable angina that required revascularization, or Q-wave MI [10]. So far, there is a lack of sufficient evidence regarding the prognosis of TVD in female patients and the impact of gender on long-term outcomes after revascularization of TVD patients remains unclear. To the best of our knowledge, this is the first study to explore sex differences in long-term clinical outcomes following revascularization among patients with TVD.
Indeed, despite the well-established similarity in incidence of CAD among women and men, women are medically managed for their coronary disease more frequently. The study by Hollenbeak et al. reveals that women with acute MI had 24% lower odds of receiving PCI after controlling for factors such as age, race/ethnicity, severity at admission, location of the infarct, or source of admission [11]. Furthermore, studies show that women tend to have a smaller body size, smaller arterial diameter, hormonal differences, atypical and delayed presentation [12].
Research shows that female patients were on average older than male patients at the time of their first invasive cardiovascular procedure. This may presumably be due to estrogen's potentiating protective effects against coronary atherosclerosis until menopause, causing a delayed CAD process [3, 13]. Despite the high risk, females tend to have less severe obstructive epicardial CAD at elective angiography and have an increased incidence of microvascular disease, coronary spasm, and spontaneous coronary artery dissection than males [14, 15]. In our study, the number of male patients who underwent revascularization was nearly three times higher than that of female patients. Furthermore, at the time of coronary revascularization, women are older and have a worse cardiovascular risk profile and other comorbidities than men [16]. In this regard, our data are consistent with previous studies.
After adjusting baseline risk profiles, there is insufficient data about gender-based differences in the long-term outcomes following coronary revascularization [17–19]. Though some studies showed opposite results (sex-related differences were observed), in more recent trials, these differences were reduced [20]. The reason may lie in the utilization of more advanced therapeutic methods, and in particular, the implantation of drug-eluting stent (DES). According to previous studies, PCI may reduce or eliminate gender differences in mortality [11, 18]. In a recent study examining the impact of gender on prognosis in ACS patients receiving DES, although women had worse baseline characteristics, no difference in long-term outcomes among sexes was observed [21]. In the present study, all patients who underwent PCI were implanted with DES were enrolled to prevent the confounding effect in the association between gender and outcome caused by using bare-metal stents [22].
In the current study, we used propensity matching for available characteristics to create groups of women and men with balanced baseline characteristics, and showed that the long-term outcomes following coronary revascularization did not differ between the two cohorts. Furthermore, in line with former studies, we found that after adjustment for advanced age and comorbidities, sex was no longer an independent predictor of MACCE. Therefore, with the latest refinement equipment and techniques, in treating patients with TVD, revascularization should be highly preferred as the treatment option and should not be limited by gender.
Study limitations
This study is retrospective and is inherently limited by its design. Despite our efforts to adjust for all preoperative variables, there were still unadjusted confounders. A selection bias for interventional therapy may also be reflected in that females represented only one-fourth of the cohort. Moreover, as all patients in our cohort have undergone revascularization (we excluded those treated only medically), so we have no data on the outcomes of conservative treatment patients. Therefore, these findings may not reflect the outcomes of all treatment modalities for TVD patients. However, we believe that this real-world registry contributes to the present understanding of TVD prognosis in females undergoing revascularization and the impact of invasive therapy in different subgroups of both genders.