We retrospectively enrolled ACS patients aged 80 years or older (n = 1,676) between January 2013 and May 2020, who entered the Cardiovascular Center of Beijing Friendship Hospital Database (CBD) Bank. The study flow chart and protocol were described in Figure 1: (1) Consecutive ACS patients aged ≥ 80 years old (n = 1,676) were enrolled. (2) All the patients were classified by gender: female group (n = 842), and male group (n = 834). (3) Within the male group, patients were categorized into the male PCI group (M-PCI group, n = 321) and the male conservative management group (M-con group, n = 513). (4) Within the female group, patients were divided into the female PCI group (F-PCI group, n = 283) and the female conservative management group (F-con group, n = 559). (5) All the patients undergoing PCI were divided into groups with (n = 118) and without MACCE (n = 486), according to whether MACCE occurred or not during the follow-up period. Clinical characteristics on admission and incidences of MACCE during follow-up were compared in different sex groups and treatment groups. Meanwhile, predictive factors for MACCE after PCI were detected and assessed in this very elderly cohort.

ACS, including ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI), and unstable angina pectoris (UAP), were diagnosed by symptoms, electrocardiogram (ECG) changes, and cardiac biomarkers. The treatment options (conservative management or PCI) were decided by two cardiologists simultaneously based on international standards and guidelines (16). The study was approved by the Institutional Ethics Committee of Beijing Friendship Hospital and was also in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

The patients' demographic information, initial clinical presentation at admission, and past medical history (hypertension, diabetes, dyslipidemia, prior MI/stroke, and smoking) were retrospectively collected from the clinical information database. Laboratory examination results included high sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), hemoglobin A1c (HbA1C), lipid spectrum, and creatinine that were measured during hospitalization. M-mode and two-dimensional echocardiography (ECHO) were performed (Philips IE33 or EPIQ 7C) for routine parameters, such as left ventricular end-diastolic diameter (LVEDD) and ejection fraction (LVEF). The characteristics of stent implantation and coronary artery were detected by angiographic and PCI procedures, presented in the medical records.

Chronic total occlusion (CTO) referred to 100% coronary artery occlusion with thrombolysis in myocardial infarction (TIMI) grade 0 flow and angiographic evidence of occlusion duration > 3 months (17). Successful PCI was defined as final residual diameter stenosis of < 20% by visual estimation and the presence of normal epicardial coronary flow (TIMI-3 flow) (18). Major hemorrhage was defined by TIMI criteria as hemoglobin decrease ≥5 g/dl or any intracranial bleeding (19). Medication after discharge was determined from the medical records or regular telephone follow-up. The primary endpoint was composite MACCE, which was the combination of non-fatal MI, stroke, heart failure requiring hospitalization (HFRH), and cardiovascular (CV) death. The secondary endpoints referred to all-cause death and each of the adverse events mentioned above. All MACCEs were confirmed by two separate cardiologists simultaneously. Regular follow-up was conducted by clinic visits or phone interviews every 1–3 months until May 2021.

Continuous variables were expressed as median with interquartile range and were compared by the Mann–Whitney U test. Categorical data were expressed as frequencies or percentages and were compared by Chi-square or Fisher's exact statistics. The events of primary and secondary endpoint were compared among F-PCI, F-con, M-PCI, and M-con groups by Chi-square test. Logistic regression analysis was conducted to identify the possible factors related to PCI treatment decision-making in the very elderly ACS cohort. Hazard ratio (HR) and 95% confidence interval (CI) were estimated by adjusting for potential confounders including sex, age, STEMI, prior stroke, smoking, creatinine, and NT-proBNP for analyses. Survival curves were conducted by the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazards analysis was used to detect and evaluate predictors for the incidence of composite MACCE between the patients with and without MACCE after PCI treatment. The multivariable model was adjusted for the following covariates in an all-enter way: age, sex, BMI, STEMI, NT-proBNP, creatinine, aspirin, P2Y12 receptor antagonist, statin, and β-blocker. A two-sided p < 0.05 was statistically significant. All the statistical analysis was conducted by the Statistical Product and Service Solutions (SPSS) software version 23.0 (IBM, Armonk, NY, USA).

The median follow-up duration of the study was 48 months (interquartile range, 24–60 m). The clinical characteristics of this very elderly ACS cohort were summarized in Table 1. Of the 1,676 patients, there was a similar proportion of men and women. Age, BMI, and types of clinical diagnosis were also matched between the sexes. But the rate of male ACS patients receiving PCI procedures was significantly higher than that of female patients (p = 0.038) (Figure 2). In past medical history, male patients had a higher prevalence of prior MI (p < 0.001) and peripheral artery disease (PAD, p = 0.011), and female patients had a greater history of hypertension (p < 0.001) and dyslipidemia (p = 0.011). As for the laboratory finding, male patients showed significantly higher levels of hs-CRP, creatinine, CK-MB, and LVEDD, compared to female patients. Meanwhile, female patients were detected to have noticeably higher levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), HbA1C, and proportion of LVEF≥50%. During the follow-up period, the percentage of men taking aspirin was significantly higher than that of women (p = 0.005).

As described in Table 2, the rate of left main (LM) lesions and three-vessel lesions were similar between male and female ACS patients who underwent PCI procedures. However, the rate of CTO in males was higher than that in females (p = 0.007). There were no significant differences in post-PCI TIMI 3 flow, procedural success rate, and stent number between the males and females.

All the baseline variables entered the logistic regression analysis to detect factors related to PCI decision-making. Based on variables identified from the univariate analysis, a multivariate analysis was conducted to screen out the independent related factors. As detailed in Table 3, the male was more likely to receive PCI treatment, which was 1.34 times higher than that of the female (HR = 1.337, p = 0.017). Furthermore, STEMI significantly drove the option of PCI strategy. However, with the declines in age, creatinine, and log NT-proBNP, it was more inclined to the PCI treatment.

Univariate Cox regression analysis identified 10 factors, which might be associated with the occurrence of composite MACCE in very elderly patients after PCI, including age, sex, BMI, STEMI, log NT-proBNP, creatinine, and the use of aspirin, P2Y12 receptor antagonist, statin, and β-blocker. Further multivariate analysis confirmed that five factors independently associated with MACCE, involving age, STEMI, log NT-proBNP, and the use of P2Y12 receptor antagonist, and β-blocker. Remarkably, gender was not a related factor to the risk of MACCE in this special population (male: HR 1.275, p = 0.236) (Table 4 and Figure 3), which meant that the predictors of MACCE after PCI were similar in both sexes in the present cohort.

The primary and secondary endpoints were displayed in Table 5. Compared to conservative management groups, PCI treatment significantly improved primary endpoints (composite MACCE) in both the male (p < 0.001) and female (p = 0.026) separately in the very elderly ACS population. Furthermore, PCI procedure significantly attenuated the risk of non-fatal MI (p = 0.032), HFRH (p < 0.001), CV death (p < 0.001), and all-cause death (p < 0.001) in male ACS patients. In addition, female patients benefited significantly from PCI treatment in the decrease of HFRH (p < 0.001), CV death (p = 0.005), and all-cause death (p = 0.006) when compared to conservative management only. Finally, there were no remarkable differences in the clinical outcomes treated with PCI between sexes during the follow-up period. Kaplan–Meier curves (Figure 4) illustrated and compared the incidences of primary and secondary endpoints of the four groups in detail.

Single-center data and retrospective design are the main limitations of the present study. Treatment strategy reflected the convention and tendency of the single center, which may have an important impact on clinical prognosis. Therefore, the conclusion may have been biased because the objectivity of the results may have been compromised. The retrospective design may miss some characteristics of the patients in the study, such as the evaluation of physical performance and acute kidney injury, which are common in the very elderly cohort (26–28). These factors might have some influences on the clinical outcomes of PCI treatment (26–28). In addition, the small sample size is also a constraint, resulting in an 8-year time span for enrolled patients, and the inability to include more stratified variables.