Two-year survival of patients with ST-segment elevation myocardial infarction according to reperfusion strategies in China: Insights from the China Acute Myocardial Infarction (CAMI) Registry

To the Editor: Contemporary guidelines recommend primary percutaneous coronary intervention (PPCI) as the gold-standard reperfusion modality in patients with ST-segment elevation myocardial infarction (STEMI) within 12 h of symptom onset.[1] However, in real-world clinical practice, the implementation of PPCI faces substantial operational challenges, particularly in resource-limited settings, such as inadequate availability of specialized cardiac catheterization teams with requisite procedural expertise or the complete absence of coronary intervention capabilities in numerous rural healthcare facilities across China.[2] Consequently, fibrinolytic therapy remains the predominant reperfusion strategy for STEMI management in county-level hospitals, with particularly high utilization rates observed in geographically remote regions.[3,4] Furthermore, our previous study revealed that 42.5% of STEMI patients fail to receive any form of evidence-based reperfusion therapy, representing a critical gap in optimal care delivery.[3] To elucidate the prognostic implications of these treatment pathways within China’s unique healthcare system, this study aimed to compare the long-term outcomes among STEMI patients receiving PPCI, fibrinolysis, and no reperfusion therapy using data from the China Acute Myocardial Infarction Registry (CAMI Registry, clinicaltrials.gov, NCT01874691). The CAMI Registry is a prospective, nationwide, multicenter observational registry study for patients with acute myocardial infarction (AMI) from 108 hospitals across 31 provinces and municipalities in China. Detail of the CAMI Registry was described previously.[3] From January 1, 2013, to September 30, 2014, 19,085 STEMI patients who were admitted within 7 days from symptom onset were consecutively enrolled [Supplementary Figure 1, https://links.lww.com/CM9/C630]. Standardized data collected during hospitalization and follow-up were recorded by trained physicians at each participating site using a web-based electronic data capture system (http://www.CAMIRegistry.org). Patient data from the system were transferred to the database center through the internet by trained investigators. Follow-up information was collected by investigators at the clinic visit or by telephone call and was rechecked by an independent team. For patients who cannot be successfully contacted, ID numbers are used to check the survival status of patients in the national registered residence system. The primary and secondary endpoints were 2-year all-cause mortality and major adverse cardiovascular and cerebrovascular events. The Ethics Committee of Fuwai Hospital and the local institution approved this study (No. 431), and written informed consent was obtained from each patient. According to different reperfusion strategies, patients were divided into three groups, namely, PPCI, fibrinolysis, and no reperfusion, and their baseline characteristics, medications, and in-hospital outcomes were compared. Continuous variables are described as mean ± standard deviation or median (Q1–Q3) and compared using analysis of variance or the Wilcoxon rank-sum test. Categorical variables are described as number (percentage) and compared using the chi-squared test or Fisher’s exact test. Crude cumulative event rates were estimated using Kaplan–Meier analysis and compared with the log-rank test. To assess the associations between reperfusion strategies and outcomes, multivariate Cox proportional hazard models were used by adjusting for potential confounding factors, including age, sex, body mass index (BMI), hospital level, current smoking, history of hypertension or diabetes mellitus, prior myocardial infarction (MI), prior stroke, peripheral artery disease, history of heart failure, early use of aspirin or P2Y12 inhibitors within 7 days, early use of statins within 7 days, symptom-to-presentation time, hemoglobin level on admission, Killip class, anterior MI, and the Global Registry of Acute Coronary Events (GRACE) risk score. To further adjust for the imbalanced baseline characteristics, propensity score-matched cohorts were built at a 1:2 ratio of the fibrinolysis and PPCI groups. The variables used for propensity score matching were the same as those used for multivariate regression. Subgroup analysis was performed according to age, sex, symptom-to-presentation time, hospital level, history of hypertension or diabetes mellitus, and Killip class. Statistical significance was defined by P <0.05 (two-tailed), with Bonferroni-adjusted P <0.017 (0.05/3.00) used for multiple intergroup comparisons. All analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC, USA) and R (R Foundation for Statistical Computing, Vienna, Austria). Among the 19,085 patients with STEMI presenting within 7 days from symptom onset, 8233 (43.1%) received PPCI, 1854 (9.7%) received fibrinolysis, and 8998 (47.1%) received no reperfusion treatment [Supplementary Figure 1, https://links.lww.com/CM9/C630]. The baseline characteristics of the patients according to reperfusion strategy are shown in Supplementary Tables 1 and 2, https://links.lww.com/CM9/C630. The non-reperfusion group had substantially delayed presentation (median [Q1–Q3]: 890 [265–2868] min) compared with the PPCI (230 [120–420] min) and fibrinolysis (150 [80–248] min) groups, exceeding the critical 12-h window for optimal myocardial salvage. This population demonstrated distinct high-risk features: advanced age, female predominance, and greater comorbidity burdens, including stroke, heart failure, and chronic kidney disease. Collectively, these factors contributed to significantly elevated GRACE risk scores. Provincial hospitals performed 46.9% of all PPCI cases, versus 5.2% by county-level hospitals (P <0.0001), whereas fibrinolysis predominated in prefecture (54.5%) and county hospitals (36.0%). Among patients with fibrinolysis, only 38.2% (708/1854) received coronary angiography, with timely angiography (≤24 h postfibrinolysis) in only 10.3% (191/1854). Supplementary Table 3, https://links.lww.com/CM9/C630 summarizes the in-hospital outcomes, complications, and discharge medications, while Supplementary Tables 4 and 5, https://links.lww.com/CM9/C630 present the endpoint incidence and Cox regression results. The crude 2-year all-cause mortality was 12.4% (95% CI: 11.9–12.9%) among all patients. The crude all-cause mortality rate was lowest in the PPCI group at 6.4% (95% CI: 5.9–6.9%), intermediate in the fibrinolysis group at 12.4% (95% CI: 10.9–13.9%), and highest in the no reperfusion group at 17.9% (95% CI: 17.1–18.7%). Compared with no reperfusion, PPCI was associated with a significantly lower unadjusted mortality risk (hazard ratio [HR] = 0.33, 95% CI: 0.30–0.37; P <0.0001), whereas fibrinolysis showed a more modest benefit (HR = 0.68, 95% CI: 0.59–0.78; P <0.0001). After multivariable adjustment, PPCI maintained a robust survival advantage (adjusted HR = 0.54, 95% CI: 0.48–0.62; P <0.0001), whereas fibrinolysis no longer significantly reduced mortality (adjusted HR = 0.92, 95% CI: 0.77–1.09; P = 0.3251) [Complete model details in Supplementary Table 4, https://links.lww.com/CM9/C630; Survival curves in Supplementary Figure 2, https://links.lww.com/CM9/C630]. Propensity score matching was conducted to compare fibrinolysis vs. PPCI outcomes [Supplementary Tables 6–8 and Supplementary Figure 3, https://links.lww.com/CM9/C630]. After matching and additional adjustment for baseline imbalances in BMI and hospital level, PPCI resulted in significantly lower 2-year mortality than fibrinolysis did (5.5% vs. 10.2%, HR = 0.54, 95% CI = 0.41–0.70, P <0.0001). Subgroup analyses stratified by symptom-to-presentation time revealed that PPCI was consistently better than no reperfusion across all time intervals (<3 h, ≥3 h to <6 h, ≥6 h to <12 h, and >12 h), with adjusted HRs for 2-year mortality of 0.42 (95% CI = 0.32–0.55, P <0.0001), 0.51 (95% CI = 0.40–0.64, P <0.0001), 0.59 (95% CI = 0.45–0.77, P <0.0001) and 0.70 (95% CI = 0.54–0.92, P = 0.0101), respectively. Fibrinolysis only reduced mortality in early presenters (<3 h, adjusted HR = 0.65, 95% CI = 0.48–0.89, P = 0.0064), with no significant benefit in later-presenting patients [Supplementary Figures 4 and 5, https://links.lww.com/CM9/C630]. Additional subgroup analyses (age, sex, hospital level, comorbidities, and Killip class) demonstrated universal survival benefits with PPCI, whereas fibrinolysis showed no significant advantage in any subgroup [Supplementary Figure 4, https://links.lww.com/CM9/C630]. The distinctive design of the CAMI study lies in its inclusion of all myocardial infarction patients within 7 days of symptom onset (unlike other registries that only enroll patients within 24 h), combined with long-term follow-up, thereby comprehensively capturing the real-world landscape of acute MI in China. Our analysis revealed significant disparities in outcomes based on the type of reperfusion therapy, with PPCI demonstrating clear superiority over fibrinolysis and no reperfusion. However, systemic challenges, including delayed presentation and limited access to PPCI, continue to hinder optimal patient outcomes. First, compared with other studies, the CAMI Registry revealed a significantly greater proportion of patients who missed reperfusion therapy due to delayed hospital presentation. Most importantly, this delayed presentation directly resulted in patients missing the critical window for timely reperfusion therapy, which was strongly associated with significantly higher long-term mortality rates. Our data showed that patients who received no reperfusion therapy had a 2-year mortality rate of 17.9%, nearly three times higher than that of those receiving PPCI (6.4%). These delays may reflect inadequate prehospital emergency response systems, transportation limitations in rural areas, low health literacy, or cultural factors delaying help-seeking behavior. Second, the efficacy of fibrinolysis is highly dependent on early administration, ideally within 3 h of symptom onset. However, our data revealed that only 48.4% of fibrinolysis-treated patients presented within this window, with a median symptom-to-presentation time of 150 minutes. This delay likely contributed to the lack of significant mortality benefit compared with no reperfusion. Importantly, for patients who initially received fibrinolysis but could be transferred to percutaneous coronary intervention (PCI)-capable hospitals, prompt referral for angiography within 3–24 h is crucial to assess reperfusion success and perform rescue PCI if needed. Our data revealed that only 38% of fibrinolysis patients underwent subsequent angiography, with merely 10% receiving it within the recommended timeframe—a critical gap in care that may have attenuated the potential benefits of pharmacologic reperfusion.[1,5] Moreover, compared with fibrinolysis and no reperfusion, PPCI was associated with significantly lower long-term mortality. However, 46.9% of PCI cases were performed in province-level hospitals, while county-level hospitals had a PPCI rate of only 5.2%. These findings reinforce the importance of regional STEMI networks, including standardized transfer protocols, to ensure timely PCI after fibrinolysis in non-PCI centers. The study had several limitations. First, the data were collected a decade ago; newer pharmacological therapies have been developed, and PPCI accessibility has improved. Although these advancements may limit the direct applicability of our findings to current practice, data from the China PEACE study—which compared STEMI management across three time periods (2001, 2006, and 2011)—demonstrated similar overall reperfusion rates but a significant increase in PPCI utilization over time.[6] Notably, our study aligns with these trends, revealing persistently high rates of treatment delays despite improved PPCI availability. Importantly, the poor long-term outcomes associated with fibrinolysis observed in our cohort remain a critical concern. Second, the use of secondary prevention medications was not systematically documented during long-term follow-up, precluding their inclusion in prognostic analyses. Thus, further studies are needed to evaluate the contemporary impact of different reperfusion strategies on long-term outcomes in Chinese STEMI patients, accounting for these evolving factors. Funding This work was supported by the Twelfth Five-Year Planning Project of the Scientific and Technological Department of China (No. 2011BAI11B02), the CAMS Innovation Fund for Medical Sciences (CIFMS) (Nos. 2020-I2M-C&T-B-050, 2016-I2M-1-009). Conflicts of interest None.