Treatment of ST-segment elevation myocardial infarction (STEMI) is based on early reperfusion therapy.1,2 A meta-analysis by Keeley et al. showed the superiority of primary percutaneous coronary intervention (PCI) over fibrinolysis in terms of mortality, reinfarction and bleeding risk.3 Current clinical guidelines stipulate that primary PCI is the preferred reperfusion therapy as long as it can be performed within 120 min of first medical contact (FMC) with the patient.1,2,4 This time interval (FMC-reperfusion) is called system delay (SD) and is directly related to prognosis.5

SD can be separated into various time intervals (Figure 1): diagnosis delay or time from FMC to an electrocardiogram showing diagnostic criteria of STEMI; the time taken to transfer the patient to a PCI-capable center (when FMC occurs outside a PCI-capable center); time from arrival at the PCI-capable center to beginning of PCI in the catheterization laboratory; and the duration of primary PCI, until coronary reperfusion is achieved. The sum of these two last time intervals is termed door-to-balloon (D2B) time.

CLAD: cath lab activation delay; D2B time: door-to-balloon time; FMC: first medial contact; PCI: percutaneous coronary intervention. a Since initiation of the new primary PCI protocol, the cardiac catheterization team is activated from the FMC site by a single phone call. b Before initiation of the new primary PCI protocol, the cardiac catheterization team was activated on the patient's arrival at our hospital.'> CLAD: cath lab activation delay; D2B time: door-to-balloon time; FMC: first medial contact; PCI: percutaneous coronary intervention. a Since initiation of the new primary PCI protocol, the cardiac catheterization team is activated from the FMC site by a single phone call. b Before initiation of the new primary PCI protocol, the cardiac catheterization team was activated on the patient's arrival at our hospital.' title='Components of ischemia time. CLAD: cath lab activation delay; D2B time: door-to-balloon time; FMC: first medial contact; PCI: percutaneous coronary intervention. a Since initiation of the new primary PCI protocol, the cardiac catheterization team is activated from the FMC site by a single phone call. b Before initiation of the new primary PCI protocol, the cardiac catheterization team was activated on the patient's arrival at our hospital.'/>

Figure 1.

Components of ischemia time. CLAD: cath lab activation delay; D2B time: door-to-balloon time; FMC: first medial contact; PCI: percutaneous coronary intervention.

a Since initiation of the new primary PCI protocol, the cardiac catheterization team is activated from the FMC site by a single phone call.

b Before initiation of the new primary PCI protocol, the cardiac catheterization team was activated on the patient's arrival at our hospital.

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The previous primary PCI protocol in our center activated the cardiac catheterization team after the patient had arrived at the hospital and the on-duty cardiology team had confirmed the diagnosis of STEMI. During normal working hours (8 am-10 pm, Monday to Friday), there is a cardiac catheterization team ready at the hospital, while after hours the cardiac catheterization team is at home. Therefore, patients presenting after hours had to wait until the cardiac catheterization team arrived at the hospital for primary PCI to be initiated.

In January 2011, a new primary PCI activation protocol was implemented in our hospital, establishing that the cardiac catheterization team would be activated by a single phone call from the FMC site: by the emergency medical services (EMS) if FMC occurred outside a medical center, or by the medical team who diagnosed STEMI if FMC occurred inside a medical center. Current clinical guidelines2 suggest this protocol, albeit without a clear recommendation.

This new protocol was intended to minimize SD by reducing the time from patients’ arrival at our center to the beginning of primary PCI, as early activation of the cardiac catheterization team could allow them to arrive at the hospital and the catheterization laboratory to be prepared while the patient is being transferred. We termed this time interval (patient's arrival at the hospital to beginning of primary PCI) the cath lab activation delay (CLAD).

Our primary objective was to determine whether the new primary PCI activation protocol has achieved its goal of reducing SD, by reducing CLAD, in STEMI patients treated with primary PCI in our hospital. In addition, the percentage of patients meeting the treatment delay targets established by the clinical guidelines1,2 was measured. Secondary objectives were to analyze the differences in SD between “working-hours” patients and “after-hours” patients, and between patients with different FMC locations.

A total of 173 consecutive STEMI patients, with FMC outside our center and less than 12 hours from symptom onset to FMC, were treated by primary PCI in our hospital during the study period, of whom 73 (42.1%) were treated before the new protocol implementation, and 100 (57.8%) were treated afterwards. The demographic and clinical characteristics of these patients are shown in Table 1. There were no significant differences between the two groups (patients treated before and after the new protocol) in factors that could delay primary PCI, such as age or Killip class IV at admission.

Regarding cardiovascular risk factors, patients treated before initiation of the new protocol had a higher prevalence of hypertension (69.9% vs. 46.0%, p=0.002) and chronic renal failure (10.9% vs. 2.0%, p=0.036). The prevalence of other cardiovascular risk factors was similar between the two groups.

Primary objective

A significant 37-min reduction in SD was observed after initiation of the new primary PCI protocol (from 166 [132–235] min to 129 [105–166] min, p<0.001) (Figure 2). CLAD was reduced by 35 min (from 55 [0–79] min to 20 [0–54] min, p=0.001), a 64% relative reduction. D2B time was also improved (absolute reduction of 34 min, p=0.005).

PCI protocol. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.'> PCI protocol. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.' title='System delay and cath lab activation delay before and after initiation of the new primary PCI protocol. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.'/>

Figure 2.

System delay and cath lab activation delay before and after initiation of the new primary PCI protocol. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.

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There were no significant differences between the groups in the time between FMC and patient arrival at our hospital (diagnosis delay plus transfer time), or in the duration of the primary PCI procedure (Table 2).

Table 2.

Analysis of ischemia time components and system delay before and after initiation of the new primary PCI protocol.

	Before primary PCI protocol	After primary PCI protocol	p
Total ischemia time
Total ischemia time	245 [189–360]	227 [180–371]	0.440
Patient delay (symptom onset to FMC)	63 [35–120]	90 [59–199]	0.058
SD
Total SD	166 [132–235]	129 [105–166]	<0.001
Sum of diagnosis delay plus transfer	93 [65–163]	74 [60–123]	0.119
CLAD	55 [0–79]	20 [0–54]	0.001
Duration of primary PCI procedure	20 [14–29]	20 [15–26]	0.972
D2B time	77 [35–96]	43 [20–73]	0.005
Clinical guidelines goals
SD ≤120 min (%)	14.5%	41.8%	0.001
CLAD=0 (%)	28.1%	44.0%	0.035

CLAD: cath lab activation delay; D2B time: door-to-balloon time; FMC: first medial contact; PCI: percutaneous coronary intervention; SD: system delay. Data are shown as median [interquartile range].

Comparison between working-hours and after-hours patients

The new primary PCI protocol is especially valuable after hours, as it allows the cardiac catheterization team to arrive at the hospital while the patient is being transferred. The percentage of after-hours patients admitted before (56.2%) and after (60.0%) the new protocol implementation was similar (p=0.613).

After hours, significant reductions of 41 min in CLAD (p<0.001), 34 min in D2B time (p=0.005) and 24 min in SD (p=0.005) were noted after initiation of the new protocol (Figure 3). The percentage of patients treated with SD ≤120 min improved from 0% to 36.6% (p<0.001), and the percentage of patients transferred directly to the catheterization laboratory on arrival (CLAD=0) almost tripled (from 15.0% to 43.3%, p=0.016). Treatment delays did not change significantly in working-hours patients, although a non-significant trend to improvement was noted (Table 3).

PCI protocol: after-hours patients. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.'> PCI protocol: after-hours patients. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.' title='System delay and cath lab activation delay before and after initiation of the new primary PCI protocol: after-hours patients. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.'/>

Figure 3.

System delay and cath lab activation delay before and after initiation of the new primary PCI protocol: after-hours patients. CLAD: cath lab activation delay; PCI: percutaneous coronary intervention.

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Table 3.

Analysis of ischemia time components and system delay before and after initiation of the new primary PCI protocol: working-hours vs. after-hours patients.

Working hours	Before primary PCI protocol initiation	After primary PCI protocol initiation	p
Total ischemia time
Total ischemia time	223 [165–398]	226 [161–361]	0.911
Patient delay (symptom onset to FMC)	60 [32–90]	90 [59–187]	0.050
SD
Total SD	151 [114–309]	125 [102–162]	0.089
Sum of diagnosis delay plus transfer	87 [41–176]	70 [60–104]	0.469
CLAD	31 [0–80]	19 [0–49]	0.407
Duration of primary PCI procedure	24 [16–32]	20 [16–26]	0.258
D2B time	59 [21–108]	41 [23–67]	0.444
Clinical guidelines goals
SD ≤120 min (%)	33.3%	47.3%	0.165
CLAD=0 (%)	45.2%	45.0%	0.409

After hours	Before primary PCI protocol initiation	After primary PCI protocol initiation	p
Total ischemia time
Total ischemia time	290 [213–356]	232 [189–411]	0.237
Patient delay (symptom onset to FMC)	90 [35–128]	90 [48–240]	0.454
SD
Total SD	170 [144–235]	146 [109–171]	0.005
Sum of diagnosis delay plus transfer	95 [75–147]	79 [60–136]	0.222
CLAD	63 [28–78]	22 [0–59]	<0.001
Duration of primary PCI procedure	19 [14–25]	19 [15–26]	0.420
D2B time	78 [41–96]	44 [17–79]	0.005
Clinical guidelines goals
SD ≤120 min (%)	0%	36.6%	<0.001
CLAD=0 (%)	15%	43.3%	0.016

CLAD: cath lab activation delay; D2B time: door-to-balloon time; FMC: first medial contact; PCI: percutaneous coronary intervention; SD: system delay. Data are shown as median [interquartile range].

Before initiation of the new protocol, after-hours patients were less likely to be treated within 120 min of SD (p=0.001) or to be transferred directly to the catheterization laboratory on arrival (p=0.005) than working-hours patients. After initiation of the new primary PCI protocol, these differences disappeared.

Analysis of treatment delays according to location of first medical contact

Our last objective was to analyze the differences between patients whose FMC had occurred in different locations (EMS, walk-in clinics and non-PCI-capable hospitals). The results are shown in Table 4.

Table 4.

Analysis of ischemia time components and system delay before and after initiation of the new primary PCI protocol, according to location of first medical contact.

Before new primary PCI protocol	EMS	Walk-in clinics	Non-PCI-capable hospitals	p
Number of patients (%)	43 (58.9)	10 (13.7)	20 (27.4)
Total ischemia time
Total ischemia time	215 [178–295]	280 [226–570]	424 [354–537]	<0.001
Patient delay (symptom onset to FMC)	60 [34–90]	91 [40–558]	105 [6–169]	0.212
SD
Total SD	147 [125–170]	199 [159–235]	280 [213–419]	<0.001
Sum of diagnosis delay plus transfer	78 [46–107]	93 [83–120]	176 [135–302]	0.001
CLAD	51 [15–78]	23 [0–77]	63 [0–81]	0.530
Duration of primary PCI procedure	20 [14–27]	22 [16–36]	21 [15–30]	0.544
D2B time	70 [35–94]	50 [22–102]	86 [66–110]	0.323
Clinical guidelines goals
SD ≤120 min (%)	17.1%	25.0%	0%	0.230
CLAD=0 (%)	23.8%	40.0%	31.5%	0.550

After new primary PCI protocol	EMS	Walk-in clinics	Non-PCI-capable hospitals	p
Number of patients (%)	71 (71.0)	12 (12.0)	17 (17.0)
Total ischemia time
Total ischemia time	214 [176–297]	212 [151–425]	448 [349–588]	0.001
Patient delay (symptom onset to FMC)	90 [48–160]	68 [60–300]	180 [100–300]	0.426
SD
Total SD	125 [104–160]	131 [112–197]	315 [175–511]	0.003
Sum of diagnosis delay plus transfer	71 [60–105]	60 [50–129]	180 [134–349]	0.007
CLAD	24 [0–57]	30 [3–54]	0 [0–45]	0.483
Duration of primary PCI procedure	19 [15–27]	22 [20–25]	21 [17–26]	0.332
D2B time	44 [18–78]	58 [27–90]	32 [22–58]	0.395
Clinical guidelines goals
SD ≤120 min (%)	46.0%	36.4%	0%	0.123
CLAD=0 (%)	43.7%	33.3%	52.9%	0.574

CLAD: cath lab activation delay; D2B time: door-to-balloon time; EMS: emergency medical services; FMC: first medial contact; PCI: percutaneous coronary intervention; SD: system delay. Data are shown as median [interquartile range].

The location of FMC for patients treated before and after initiation of the new primary PCI protocol did not differ significantly (p=0.205). In both groups (before and after new protocol implementation), longer SD (p<0.001) and total ischemia time (p<0.001) were observed in patients with FMC in non-PCI-capable hospitals (Figure 4). This was related to a longer transfer time (p<0.001). No differences were noted in treatment delays once patients arrived at our hospital (D2B time, CLAD).

PCI protocol. 2: After initiation of the new primary PCI protocol. EMS: emergency medical services; PCI: percutaneous coronary intervention.'> PCI protocol. 2: After initiation of the new primary PCI protocol. EMS: emergency medical services; PCI: percutaneous coronary intervention.' title='System delay according to location of first medical contact. 1: Before initiation of the new primary PCI protocol. 2: After initiation of the new primary PCI protocol. EMS: emergency medical services; PCI: percutaneous coronary intervention.'/>

Figure 4.

System delay according to location of first medical contact. 1: Before initiation of the new primary PCI protocol. 2: After initiation of the new primary PCI protocol. EMS: emergency medical services; PCI: percutaneous coronary intervention.

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Importantly, no patient transferred from a non-PCI-capable hospital achieved SD ≤120 min.

Reduction of ischemia times in STEMI is a priority goal for contemporary health systems. Several regional programs with this purpose have shown promising results,8–11 and various prehospital primary PCI activation strategies (similar to that initiated in our hospital, but with smaller sample sizes) have achieved improvements in ischemia times.12,13

SD is the best ischemia time interval to evaluate a regional primary PCI network, as it involves the coordination of all of the network's components. Furthermore, it is directly related to in-hospital mortality in STEMI.5,14,15 Our new protocol achieved a 35-min reduction in CLAD and a 37-min reduction in SD. There were no significant differences between the sum of diagnosis delay plus transfer time, or in the duration of primary PCI, which implies that the observed SD reduction was mainly driven by the improvement in CLAD.

It was not the objective of our study to determine whether such improvements have prognostic consequences, but previous studies have shown that reductions of 30 min or more in SD are associated with lower in-hospital mortality.16 Furthermore, we observed a non-significant reduction in infarct size, estimated by peak creatine kinase and troponin I levels, with the new protocol. This reduction was statistically significant for the subgroups of patients who benefited most from the new protocol, i.e. after-hours patients and those with FMC in other than a non-PCI-capable hospital.

Recently, the mean system delays of different European countries during the year 2009 were published,17 ranging from 60 min in Belgium to 177 min in Serbia. The mean SD in Spain was 98 min. Another recent study in Barcelona city (Spain) observed an SD of 85 (66–110) min.11 In the USA, the median D2B time at the end of 2010 was 64 min.18

The treatment delay once patients arrive at our hospital (D2B time) was similar to that in other western countries.17,18 However, the sum of diagnosis delay and transfer time in our study was higher, which explains the observed SD differences. In a recent US registry, transfer time (without including diagnosis delay) was 35 (25–49) min for patients with out-of-hospital FMC,18 while the sum of diagnosis delay plus transfer time was 71 (60–105) min in our study after initiation of the new primary PCI protocol.

Previous studies have demonstrated that direct transfer to the catheterization laboratory when patients arrive at the hospital reduces ischemia times and improves survival.19–21 Our new primary PCI protocol was designed to achieve this goal (CLAD=0), as prehospital activation of the cardiac catheterization team may enable them to arrive at the hospital and prepare the catheterization laboratory before the patient's arrival. Concerning this objective, the percentage of patients transferred directly to the catheterization laboratory on hospital arrival rose from 28.1% before initiation of the new protocol to 44.0% afterwards.

Nevertheless, achieving CLAD=0 depends on different factors according to the time of the day. During working hours, as there is a cardiac catheterization team at the hospital, CLAD is determined by the availability of a free catheterization laboratory ready for the procedure. Prehospital activation can make this more feasible, but the actual influence on SD may be small. By contrast, after hours, CLAD depends on activation of the cardiac catheterization team plus patient transfer time, as there is virtually always a free catheterization laboratory. For this reason, the new primary PCI protocol was intended to improve treatment delays, especially after hours. The observed results support this premise.

The lack of in-hospital cardiac catheterization teams in several PCI-capable centers after hours explains the longer treatment delays observed in after-hours patients in various registries.22,23 Before initiation of the new primary PCI protocol, this was also seen in our hospital, but, importantly, the new protocol has succeeded in eliminating the differences in treatment delays between working-hours and after-hours patients.

Finally, the differences in SD between patients with various FMC locations were analyzed. In agreement with other studies,21 SD was longer in patients with FMC in non-PCI-capable hospitals, due to a longer transfer time. This is due to the distance from these non-PCI-capable hospitals to our hospital (which ranges from 16.2 km to 89.8 km), and to the lack of on-site ambulances with advanced life support: the referring hospitals must call a central ambulance coordinating center, which sends the nearest available ambulance with advanced life support to the hospital to pick up the patient. Hence, ambulances must make a time-consuming back-and-forth journey.

In a recent US study,14 patients with FMC in non-PCI-capable hospitals lost the chance of being treated with a SD ≤120 min when the traveling time between the FMC center and the PCI-capable hospital was greater than 45 min. Regional STEMI treatment programs should consider geographical and local transport criteria in order to make primary PCI the reperfusion treatment for the majority of patients, and, conversely, to define fibrinolysis as the first-choice treatment for patients with FMC far from a PCI-capable hospital.

In conclusion, the new primary PCI protocol, which included the prehospital activation of the cardiac catheterization team, resulted in a significant reduction of 37 min in SD. There was an absolute increase of 27.3% in the percentage of patients treated with SD ≤120 min.

The authors have no conflicts of interest to declare.