Sex differences in mortality after percutaneous coronary intervention: a contemporary nationwide registry and prospective cohort analysis

Introduction

Despite advances in cardiovascular care, coronary artery disease (CAD) remains the leading cause of death worldwide. Previous research has demonstrated increased mortality rates among women compared to men following percutaneous coronary intervention (PCI) (1-5), though some registries show no significant difference (6,7). While both genders share common risk factors for mortality following PCI, such as hypertension (HT), dyslipidemia (DLP), chronic kidney disease (CKD), and smoking (8,9), the magnitude of their impact may differ.

Specific gender-related factors contribute to the observed sex-based mortality disparity. Females undergoing PCI are often older and present with a greater burden of comorbidities compared to males. Additional contributing risk factors include biological sex differences, such as smaller arterial diameters that may lead to technical difficulties during procedures, and sociocultural factors, such as the presentation of atypical symptoms leading to treatment delays (10-21).

Previous clinical practices have attempted to reduce this sex-based mortality disparity, but data on the specific medical care and risk factors related to in-hospital mortality have been limited. Therefore, this study aimed to identify the risk factors associated with in-hospital mortality in men and women within the Thai PCI registry to ultimately enhance patient healthcare services, optimize clinical outcomes, and improve the utilization of healthcare resources. We present this article in accordance with the STROBE reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-25-97/rc).

Methods

The Cardiac Intervention Association of Thailand (CIAT) initiated the Thai PCI Registry, a prospective, multicenter study that enrolled 19,701 patients between November 2015 and May 2018. All catheterization laboratories in Thailand were invited to participate, with 39 hospitals across the country ultimately contributing data voluntarily. The detailed methodology for the registry has been published previously (22).

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The Registry was approved by the Central Research Ethics Committee of Thailand (COA-CREC 006/2018). Further details are available on the CIAT website. Research nurses at local sites systematically recorded all data—including patient characteristics, procedural specifics, equipment and medication use, complications, and in-hospital outcomes—using a specifically-developed electronic case record form (eCRF).

The definitions used in this study were consistent with previous reports (22). Urgent PCI was defined as a semi-urgent procedure requiring a short waiting time for execution, performed within 72 hours, depending on the patient’s condition and medical facility readiness. Emergency PCI was defined as a procedure that must proceed as soon as possible. Arrhythmias requiring treatment were defined as those necessitating additional medication or intervention, such as tachyarrhythmias (e.g., ventricular fibrillation or ventricular tachycardia requiring defibrillation) or bradyarrhythmias (e.g., heart block) requiring a temporary pacemaker. Procedure complications were defined as the presence of a residual dissection, perforation, no-reflow phenomenon, major side branch occlusion, acute stent thrombosis, catheter thrombosis, device loss, dislodgement, or rupture. Procedural failure was defined as a treatment result with a residual stenosis of greater than or equal to 50% after plain old balloon angioplasty (POBA), or greater than or equal to 20% after stenting.

Statistical analysis

Continuous variables were presented as mean ± standard deviation (SD) or median and interquartile range (IQR), as appropriate. Categorical variables were described as a frequency and percentage (n, %). The age distribution was divided into four groups: below 45 years (premenopausal), 45 to 59 years (before retirement), 60 to 80 years, and over 80 years.

Differences between the sex groups for continuous variables were computed using the t-test or the Mann-Whitney U test, where appropriate. Categorical variables were compared using the χ² test or Fisher’s exact test. A simple logistic regression model was constructed to assess risk factors for in-hospital mortality, stratified by sex. Risk factors with a P value of< 0.1 in this step were simultaneously considered in a multivariate model. Only significant variables, as suggested by a likelihood ratio (LR) test were retained in the final multivariate logistic regression model. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. Statistical significance was defined as a two-sided P value of <0.05. All analyses were stratified by sex and performed using STATA version 17.0 (Stata Corp., College Station, TX, USA).

Study endpoints

The primary endpoint of this study was in-hospital mortality, defined as death from any cause during hospitalization after a PCI. The main cause of patient death was categorized into one of the following options: cardiac (heart disease, sudden death of unknown cause), neurologic, renal, vascular, infection and pulmonary (22).

Results

This study utilized a nationwide registry to examine sex differences in outcomes among 19,701 patients who underwent percutaneous coronary intervention (PCI) (22). The analysis revealed that women undergoing PCI were older than men (mean age: 67.3±11.3 vs. 62.8±11.6 years, P<0.001). This age disparity was further highlighted by the higher proportion of octogenarians among female patients (13.5%) compared to male patients (7.1%) (Table 1).

Baseline characteristics showed women had a higher prevalence of traditional risk factors. Common cardiovascular risk factors—such as HT, DLP, type 2 diabetes mellitus (T2DM), being underweight, prior heart failure, prior valvular surgery, and CKD—were more prevalent in women. Men, conversely, were more likely to smoke, present with ST-elevation myocardial infarction (STEMI), and undergo emergency PCI. Other risk factors, including cerebrovascular accident (CVA), peripheral artery disease (PAD), prior coronary artery bypass grafting (CABG), family history of premature CAD, prior MI, and known CAD, did not differ between the two groups. Regarding health coverage schemes, more women were using universal coverage (68%) than men (61.7%).

STEMI and emergency PCI were more frequent in men, whereas non-ST-elevation myocardial infarction (NSTEMI) and stable CAD occur more frequently in women. Additionally, the time to PCI for STEMI was delayed in women, averaging 9.0 hours compared to 7.4 hours in men (Table 1).

Regarding anatomical coronary vessels, women exhibited a higher prevalence of left main (LM) and triple-vessel disease (TVD) compared with men, though anatomical complexity in types B and C did not differ significantly between the sexes. Procedurally, women showed higher prevalence in femoral access, multiple attempts, crossover procedures, and rotablator use, while men more frequently utilized radial access; pharmacologically, men were more commonly administered glycoprotein (GP) IIb/IIIa inhibitors, ticagrelor, and prasugrel. Women experienced higher in-hospital (3.5% vs. 2.3%; P<0.001) and 1-year mortality rates (13.4% vs. 9.1%; P<0.001) and tended towards higher procedural complications (5.7% vs. 5.0%; P=0.04), with bleeding, endotracheal tube (ET-tube) use, and heart failure more prevalent in women (Table 2).

Factors associated with in-hospital mortality also varied by sex (Table 3). The in-hospital death rate increased with age for both sexes. Regarding the underlying diseases, a history of CVA (OR 2.53, P<0.001) was primarily associated with increased mortality in women. In men, factors associated with mortality included current smoking (OR 1.66, P<0.001), a history of prior valve surgery or procedure (OR 3.36, P=0.02), LM CAD (OR 3.30, P<0.001), vascular complications requiring intervention (OR 5.87, P<0.001), and bleeding complications (OR 2.65, P<0.001). Procedural failure and the use of GP IIb/IIIa inhibitors impacted mortality in both groups, but they had a more pronounced effect in women (procedural failure: OR 3.93, 95% CI: 2.63–5.88, P<0.001 among women vs. OR 2.65, 95% CI: 1.86–3.78, P<0.001 among men; GP IIb/IIIa inhibitors: OR 4.36, 95% CI: 2.95–6.42, P<0.001 among women vs. OR 2.85, 95% CI: 2.10–3.86, P<0.001 among men). Emergency PCI was also an impact factor for both groups, with a greater impact in women (OR 29.87, 95% CI: 18.46–48.32, P<0.001 among women vs. OR 17.86, 95% CI: 12.48–25.54, P<0.001 among men).

After adjusting for baseline variables (as shown in Table 4 and Figure 1), both femoral access and procedural complications were identified as statistically significant mortality risks for both sexes. Several risk factors were significant for both genders but demonstrated a greater impact on women compared with men: emergency PCI presentation (OR 14.01, 95% CI: 8.03–24.43, P<0.001 among women vs. OR 3.77, 95% CI: 2.19–6.50; P<0.001 among men), urgency (OR 5.58, 95% CI: 3.08–10.09, P<0.001 vs. OR 2.74, 95% CI: 1.64–4.58, P<0.001), new required dialysis (OR 7.10, 95% CI: 2.84–17.77, P<0.001 vs. OR 3.28, 95% CI: 1.83–5.86, P<0.001), arrhythmia requiring treatment (OR 3.66, 95% CI: 2.33–5.75, P<0.001 vs. OR 3.09, 95% CI: 2.22–4.29, P<0.001), and procedure failure (OR 3.41, 95% CI: 1.95–5.96, P<0.001 vs. OR 1.85, 95% CI: 1.16–2.95, P=0.01). Mortality risk factors also exhibited sex-specific differences. In men, the identified risk factors included HT, heart failure, PAD, STEMI, NSTEMI, prior valvular surgery, and LM CAD. Conversely, in women, the key mortality risk factors were a history of CVA (OR 2.43, 95% CI: 1.43–4.12; P=0.001), cardiogenic shock (CS) at the start of PCI (OR 5.61, 95% CI: 3.85–8.15, P<0.001), and CKD (OR 2.73, 95% CI: 1.90–3.93, P<0.001).

Figure 1 Factors associated with in-hospital mortality stratified by gender: a multivariate analysis. CAD, coronary artery disease; CI, confidence interval; CKD, chronic kidney disease; DVD, double vessel disease; HR, hazard ratio; NSTEMI, non-ST-elevation myocardial infarction; OR, odds ratio; PCI, percutaneous coronary intervention; SBP, systolic blood pressure; STEMI, ST-elevation myocardial infarction; SVD, single vessel disease; TVD, triple vessel disease.

Discussion

The principal finding was a higher in-hospital mortality rate for women undergoing PCI compared to men (3.5% vs. 2.3%, P<0.001). In women, in-hospital mortality was significantly associated with a history of CVA, the presence of CS at the start of the procedure, and CKD. The 1-year follow-up mortality rate was also significantly higher in women than in men (13.4% vs. 9.1%, P<0.001). These findings are consistent with previous studies, which reported that women with acute myocardial infarction had both lower rates of invasive procedure uptake and a higher in-hospital mortality rate than men (1,3,4,23). According to the 2014 Global Gender Gap Report by the World Economic Forum, Thailand ranked 61 out of 142 countries, indicating persistent gender disparity in economic participation, educational attainment, health, and political empowerment (24). This disparity may also extend to health outcomes, as evidenced by CAD data from the United States, where the estimated prevalence is higher in men (60%) than in women (40%) (25,26). Similarly, the Thai PCI registry reported a prevalence of PCI that was twice as high in men as in women. However, significant data gaps remain regarding the overall prevalence of CAD within Thailand.

Prior research indicates that women typically develop clinical manifestations of CAD approximately 10–20 years later than men and are more likely to receive undertreatment (27-29). Consistent with this finding, a Thai PCI registry study reported a two-fold higher prevalence of CAD among octogenarian women compared to men (13.5% vs. 7.1%). This delayed presentation of ischemic heart disease in women was also associated with a higher prevalence of cardiovascular risk factors (for example, T2DM, CKD, PAD, and history of CVA) and appeared to have a more significant impact on mortality risk compared to men (30-35).

Women with CKD experience an attenuation or loss of their inherent survival advantage over men. This disparity is attributed to a complex interaction of hormonal changes, resulting in a greater excess mortality burden in women. Biological factors contributing to this trend include the loss of estrogen’s protective effect. In the general population, estrogen confers a protective effect against cardiovascular disease. In the context of CKD, the production and balance of sex hormones are altered, which may eliminate this cardioprotective effect in women, particularly post-menopause or in advanced stages of CKD. Additionally, women with CKD exhibit a distinct vulnerability to the impact of cardiovascular disease. Some studies suggest that when these women develop cardiovascular complications, the impact is more severe, leading to disproportionately higher mortality rates compared to men with similar conditions. There is also a differential impact of risk factors, as high albuminuria appears to have a greater effect on cardiovascular risk in women than in men (36,37).

Furthermore, CKD negatively impacts the prognosis of CAD. Patients with CKD exhibit a higher prevalence of severe and complex coronary lesions, such as multivessel and LM artery disease (38-40). CKD patients presenting with STEMI frequently experience hemodynamic instability, which is associated with increased in-hospital mortality (41). In this study, CKD was more prevalent and significantly impacted mortality risk, specifically in women (OR 2.73, 95% CI: 1.90–3.93, P<0.001). The need for newly initiated dialysis was identified as a serious complication associated with mortality risk in both women (OR 7.10, 95% CI: 2.84–17.77, P<0.001) and men (OR 3.28, 95% CI: 1.83–5.86, P<0.001); however, this association was more pronounced in women.

Various studies demonstrate significant sex-based differences in the severity and etiology of CVA. The severity of CVA is reportedly higher in women than in men, with distinct underlying causes observed. Men typically exhibit large artery atherosclerosis, whereas women present with more cardiac embolic strokes, a difference attributed to a higher incidence of atrial fibrillation in women (42,43).

Increased cardiovascular and cerebrovascular mortality in women is linked to biological mechanisms such as myocardial infarction with non-obstructive coronary arteries (MINOCA), hormonal changes after menopause, and female-specific risk factors related to pregnancy. These factors lead to worse outcomes because MINOCA is often missed on standard angiography, while hormonal shifts accelerate vascular aging and HT, and pregnancy complications are underrecognized risk factors for future events.

In this study, a history of CVA was significantly associated with increased mortality in women (OR 2.43, 95% CI: 1.43–4.12, P=0.001). Additionally, a later clinical presentation and a higher burden of conventional cardiovascular risk factors were associated with worse outcomes for women.

In patients undergoing PCI, CS at the time of intervention was associated with the most severe clinical presentation. Prior research has shown that women have a higher mortality in CS cases, possibly because they were less likely to receive percutaneous left ventricular assist devices (LVADs) but more likely to receive inotropes (44). Other research has found that women have a higher mortality rate during the first eight days after intra-aortic balloon pump (IABP) insertion, with older age, more comorbidities, and mechanical complications identified as independent risk factors (45,46).

In the present study, CS present at the start of PCI was a risk factor exclusively in women (OR 5.61, 95% CI: 3.85–8.15, P<0.001). Multiple factors contribute to worse outcomes in women. Clinically, women were older and had a higher burden of comorbidities compared to men. Furthermore, atypical symptoms that can delay diagnosis and treatment, combined with smaller vessel anatomy that impedes device insertion and increases the risk of procedural failure, contribute to a more severe presentation.

Contributing factors, such as difficulties with vascular access and post-PCI complications, were more common in women and contributed to higher mortality rates. Previous studies had identified several risk factors for vascular complications that were more prevalent in women. These included a smaller radial artery diameter at the access site, which could increase bleeding risk, particularly when switching from a radial to a femoral approach due to difficulties such as an artery being too small, spastic or requiring a larger catheter. Comorbidities such as being underweight and being elderly were also associated with complex coronary lesions, leading to technical difficulties during procedures. Additionally, women’s smaller-caliber coronary arteries and a higher prevalence of plaque erosion may increase the risk of restenosis and stent thrombosis, both of which have been shown to contribute to suboptimal PCI outcomes in women (18-20,46,47).

In our study, women experienced a slightly higher prevalence of both vascular complications (0.4% vs. 0.3% in men) and procedural complications (5.7% vs. 5.0% in men); however, these differences were not statistically significant when compared with men Furthermore, several risk factors associated with vascular complications were more prominent in women, including a higher rate of multiple arterial access attempts (7.7% vs. 5.4%) and a greater prevalence of being underweight (7.4% vs. 6.2%). Women also presented with an older age and more complex coronary lesions (Class C: 63.0% vs. 61.9%) at the time of the event. Other mortality factors identified were delayed time to treatment, under-recognition of heart disease, and differences in clinical presentation that often led to less aggressive treatment strategies for women. Delayed initiation of critical medication and revascularization procedures was also more common in women, and emergent PCI was a more significant mortality factor for women than for men (10,11,21,48).

The influence of factors potentially associated with female sex on clinical outcomes may involve variables that are currently unknown. This could lead to an apparent association with adverse outcomes, even though other causative factors (e.g., hormonal status, endothelial dysfunction, or microcirculation disorders) may be involved.

In the future, an intensive focus on modifiable cardiovascular risk factors, time to first medical contact (21,48), and awareness of peri-procedural care may lead to the use of advanced devices and techniques [e.g., using drug-eluting stents (DES), evaluating vessel size and morphology by intravascular ultrasound (IVUS) or optical coherence tomography (OCT)] in women, ultimately reducing their mortality rate (6,46).

Limitations

This study has several limitations. Primarily, reliance on registry data can introduce selection bias (e.g., incomplete recording of patient demographics or procedural details) and result in a lack of data on long-term outcomes. Secondly, the study failed to sufficiently analyze female-specific risk factors for CAD, including pregnancy-related complications such as gestational diabetes, pregnancy-induced hypertension, and preeclampsia (49); emotional stress associated with stress cardiomyopathy (50,51); and autoimmune processes like systemic lupus erythematosus and rheumatoid arthritis, which can induce atherosclerosis (52).

Conclusions

Women undergoing PCI experienced significantly higher in-hospital and one-year mortality rates compared with men. Key risk factors contributing to this increased mortality in women include a history of stroke, CS, and CKD. While emergency or urgent PCI procedures, the need for dialysis initiation, the presence of arrhythmias, and procedure failure negatively affect both sexes, their impact appears to be more pronounced in women. Improving patient prognosis requires increased clinical attention to women’s specific needs and enhanced awareness of appropriate peri-procedure care to mitigate these disparities.

Acknowledgments

The authors thank the Health Systems Research Institute (HSRI) and DMU for their support and for assistance with data analyses. The authors also thank Mr. Bryan Roderick Hamman for his assistance with the English-language presentation of the manuscript.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-25-97/rc

Peer Review File: Available at https://atm.amegroups.com/article/view/10.21037/atm-25-97/prf

Funding: This study was funded by the Health System Research Institute of the Ministry of Public Health in Thailand.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-25-97/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The Registry was approved by the Central Research Ethics Committee of Thailand (COA-CREC 006/2018).

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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