Acute coronary syndrome (ACS) remains one of the main causes of death and morbidity in developed countries,1,2 reflecting the limited translation of cardiovascular research achievements into clinical practice. Several factors and processes contribute to this gap between knowledge and practice, some of which is due to treatment delays.

In the management of ACS, the benefits of early reperfusion of patients presenting with ST-segment elevation myocardial infarction (STEMI) are well established.3,4 According to international guidelines, primary percutaneous coronary intervention (PCI) should be performed within 90 min of first medical contact (FMC), and if performed within 120 min of FMC, it is preferable to fibrinolysis.5 However, the optimal reperfusion strategy and timing for patients presenting with non-ST-elevation acute coronary syndromes (NSTE-ACS) are less clear. NSTE-ACS patients are a heterogeneous population, ranging from low-risk patients who may benefit from conservative treatment, to high-risk patients with an increased risk of death and cardiovascular events, who require invasive coronary angiography and revascularization. There is growing evidence supporting the benefits of a routine invasive strategy in patients with a high-risk profile.6,7 However, the optimal timeframe for invasive strategies remains controversial. Despite this, the most recent European Society of Cardiology (ESC) guidelines recommend an immediate invasive strategy (<2 hours) in very high-risk patients, an early invasive strategy (<24 hours) in high-risk patients, and an invasive strategy (<72 hours) in intermediate-risk patients.8

Complying with these guidelines would require the already overburdened healthcare system to provide timely care to more patients, which would then entail reorganization so as to meet these standards and to improve efficiency. Furthermore, since patients are responsible for initiating the cascade of events associated with the treatment pathway, it is also important to analyze patient-related delays. Thus, the purpose of this study is to assess patient and system delays, according to diagnosis and risk profile, and to identify predictors of prolonged treatment delays.

NSTE-ACS patients were significantly older than those with STEMI (Table 1). High-risk NSTE-ACS patients were less often men, Porto inhabitants, and partnered, were less educated and had lower income. The prevalence of cardiovascular risk factors was greater among NSTE-ACS patients, except for a history of smoking, which was more frequent in those with STEMI. Overall, nearly 60% of the patients used their own means of transportation to seek healthcare services, nearly 15% chose primary healthcare centers as their first healthcare provider, and just over half were admitted directly to a PCI-capable hospital.

Median time between symptom onset and FMC was 90 min (IQR: 46-210), 140 min (60-420), and 123 min (60-390) for STEMI, high-risk NSTE-ACS, and intermediate-risk NSTE-ACS patients, respectively (Figure 2). Symptom onset-FMC delay greater than 120 min was more frequent in the high-risk NSTE-ACS group (57.7%), followed by intermediate-risk NSTE-ACS (52.1%) and STEMI (43.3%). Patients who correctly attributed their symptoms to the heart were less likely to experience a delay between symptoms and FMC ≥120 min, although the difference was statistically significant only for those with STEMI (Table 2). By contrast, the risk of prolonged delay was greater for patients who used their own transportation, compared with ambulance use. Among high-risk NSTE-ACS, patients from the north-east region had a higher risk of prolonged delay than patients from Porto, whereas among intermediate-risk NSTE-ACS, patients with diabetes had a lower risk of prolonged delay.

Figure 2.

Patient and system delays according to diagnosis and risk stratification. HR: high-risk; IR: intermediate-risk; NSTE-ACS: non-ST-elevation acute coronary syndrome; STEMI: ST-elevation myocardial infarction.

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Regarding system delay, median time between FMC and PCI was 177 min (95-435) for STEMI patients, and 78.0% experienced a delay exceeding 90 min (Figure 2). Median time between FMC and angiography was 30.9 hours (20.3-70.2) for high-risk NSTE-ACS and 26.6 hours (17.1-52.0) for intermediate-risk NSTE-ACS; the delay exceeded the recommended timeframes in 65.8% of patients with high-risk NSTE-ACS and in 14.2% of those with intermediate-risk NSTE-ACS. Patients living in the north-east region were more likely to be treated beyond the recommended timeframe, although the differences were not statistically significant in all groups (Table 2). The risk of delay >90 min was nearly six-fold higher for patients with STEMI admitted to non-PCI-capable hospitals, while for high-risk NSTE-ACS, patients with hospital admission during the weekend, impaired renal failure, and in Killip class III-IV were more likely to have delays ≥24 hours between FMC and angiography.

The proportion of patients with delays between symptom onset and FMC >120 min could have been reduced by nearly 50% for STEMI and 25% for intermediate-risk NSTE-ACS if all patients had correctly recognized their symptoms and had been transported by ambulance (Table 3). Further, the proportion of STEMI patients with delays beyond the recommended timeframe could be reduced by around 10% if all patients were admitted directly to a PCI-capable hospital.

Despite the recognized benefits of timely treatment for ACS and substantial investment in this area, a large proportion of patients still fail to receive treatment within recommended timeframes. Nearly one-half of the patients in our study experienced delays ≥120 min from symptom onset to FMC. The use of prehospital ambulances and the correct interpretation of symptoms, both of which can be improved by educational interventions, were found to play a key role in patient delays. Moreover, system delays exceeded the recommendations for 78% of STEMI patients and 66% of higher-risk NSTE-ACS patients. Admission to a PCI-capable hospital was associated with shorter delays for patients with STEMI, whereas admission during weekends and complications at admission were associated with prolonged system delays for patients with high-risk NSTE-ACS.

The implementation of various American (D2B Alliance, Mission: Lifeline) and European (Stent for Life) initiatives has aimed to increase the proportion of STEMI patients with timely access to primary PCI.10,11 In Portugal the Stent for Life initiative was implemented in 2011, however, four years later, no significant differences were observed in symptom onset-FMC time (114 min in 2011 vs. 119 min in 2015).12,13 Median STEMI patient delays in our study are lower, but nearly half of patients continue to experience delays of ≥120 min from symptom onset to FMC. Several recent European studies have documented similar proportions, in some cases unchanged over time.14,15

Studies on delays specifically among NSTE-ACS patients are scarce and analyze only prehospital delays (time between symptom onset and hospital presentation), rather than patient delays.16–20 These studies, although not directly comparable to ours, identify patient delay as a major contributor to prehospital delay. Similarly to our results, in the CRUSADE study, which analyzed 104 622 NSTE-ACS patients, median time from symptom onset to hospital presentation was 156 min and the delay was ≥120 min for 59% of the patients.16

Additionally, our findings suggest that patients with STEMI sought treatment earlier than patients with NSTE-ACS, in line with previous reports.17–19 Since patients typically cannot identify the type of ACS they are experiencing, there may be a link between pathophysiological processes and symptom severity that expedites STEMI patients’ decision to seek healthcare services; in our study patients with STEMI reported higher pain intensity. The differences in patient delays may also be explained by the different characteristics of NSTE-ACS and STEMI patients. In comparison with STEMI patients, NSTE-ACS patients were more frequently women, older, and had a higher prevalence of chronic health conditions. Such patients are more likely to experience atypical symptoms,21 which may be associated with longer delays.

Regardless of diagnosis and risk stratification, the correct interpretation of symptoms and the use of ambulances were associated with shorter patient delays. These factors have previously been found to be associated with timely access to reperfusion among STEMI patients.12,13,22,23 Furthermore, patients who recognize their symptoms as cardiac were more likely to use emergency ambulances,24 which can result in a 30-minute reduction in delay from symptom onset to presentation.22 Our results show, however, that nearly one-half of patients did not attribute their symptoms to the heart, nor did they use prehospital ambulances. Therefore, considerably more effort could be put into educating communities, as well as individuals, about symptom awareness and efficient healthcare-seeking behavior.25 We estimate that the proportion of patients with delays of ≥2 hours could be reduced by nearly 50% if all patients correctly attributed their symptoms to the heart and used ambulances to reach healthcare facilities.

The proportion of patients with STEMI who, due to system delays, fail to receive treatment as recommended remains high. System delays exceeded 90 min in approximately 75% of STEMI patients, which echoes previously published studies in Portugal.13,26 Similar results from Finland suggest there have been no substantial improvements in system delays over time, as the percentage of patients with treatment delays exceeding 90 min only decreased from 77% in 2007-2008 to 75% in 2011-2012.15 The median system delay in our study coincided with the upper limit of the range (60-177 min) reported in a European study on 30 countries.27 These findings call for more effort in addressing modifiable healthcare system factors that may explain this delay.

The healthcare system is failing to manage STEMI patients with early invasive strategies, but its performance has affected NSTE-ACS patients as well, since two-thirds of patients with high-risk NSTE-ACS were treated beyond 24 hours. Data from the Portuguese Registry on Acute Coronary Syndromes show that, between 2002 and 2015, there were significant increases in the proportion of patients who underwent coronary angiography within 24 hours.28 However, in 2015 still one-half of patients were treated beyond the recommended time limit,28 which is similar with the proportion reported in a recent study from the SWEDEHEART registry.29 These results support the notion that using existing tools is a key priority to improve risk stratification and adherence to early invasive strategies for higher-risk patients.

Transfer from a non-PCI-capable hospital was the strongest predictor of delay >90 min among STEMI patients, a finding which is in line with previous studies.30,31 Furthermore, patients from the north-east region experienced prolonged system delays, which may be explained by the long transfer distances in rural areas. Although the region itself was not an independent predictor of delays, patients living in rural areas were more likely to be referred to a non-PCI-capable hospital, leading to longer delays.32 In our study, almost half of the patients from the north-east region lived more than 60 min away from the nearest PCI-capable hospital, while such patients accounted only for a very small proportion in the Porto district. Several studies have reported that direct referral to PCI-capable hospitals, along with prehospital electrocardiograms, enables STEMI patients from rural populations to have timely access to PCI.33,34 In this context, the heterogeneous geographic distribution of healthcare resources in Portugal may require adjustments in the healthcare system in order to ensure more equitable access to treatment for ACS, particularly in rural areas. Additionally, high-risk NSTE-ACS patients whose symptoms appeared during the weekend were more likely to experience prolonged system delays. This may be partially explained by the time that the hospitals needed to assemble on-call staff and activate the cardiac catheterization laboratory during off-hours. Finally, admission characteristics related to impaired renal function and Killip class were found to be associated with prolonged system delays for NSTE-ACS patients. These findings may be explained by such patients’ need for more complex stabilization in the acute care phase.30

This study offers valuable new insights into predictors of both patient and healthcare system delays affecting ACS patients, thus contributing to a better understanding of variations in treatment. Despite its methodological strengths, including a high participation rate and detailed prospective patient characterization collected by trained staff, certain limitations of the study must be acknowledged. First, patients who died before arriving at the hospital or in the hospital emergency department, and patients admitted to other hospital departments, were not included in the study. As these patients are expected to have experienced longer delays, our results might underestimate time delays. Second, although data were collected within 48 hours of admission, we cannot rule out that recall bias might have occurred in some patients. Lastly, our results may not be generalizable to other regions in the country, although the study was conducted in two different settings, one mainly coastal and urban and the other mainly rural and inland, which enabled the comparison of relevant factors regarding access to health care.

Due to both patient and system delays, a large proportion of STEMI and high-risk NSTE-ACS patients still fail to have access to timely reperfusion. To improve implementation of the guidelines, symptom awareness and the use of prehospital ambulances should be improved. In addition, the healthcare system should ensure that patients in all geographic locations receive timely reperfusion and that STEMI patients have direct access to PCI-capable hospitals, while also addressing the variation in care during weekends.

This study was supported by the European Regional Development Fund (ERDF), through the Operational Programme “Competitiveness and Internationalization”, and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Education and Science (FCOMP-01-0124-FEDER-028709), under the project “Inequalities in coronary heart disease management and outcomes in Portugal” (FCT PTDC/DTP-EPI/0434/2012) and the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013).

The authors have no conflicts of interest to declare.