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A Regional System for Delivery of Primary Percutaneous Coronary Intervention (Full title below)
A Regional System for Delivery of Primary Percutaneous Coronary Intervention in ST- Elevation Myocardial Infarction: STEMI-St. Cloud
ABSTRACT: Background. Strategies of emergency care in the treatment of ST-segment elevation myocardial infarction (STEMI) have evolved rapidly over the past two decades to include primary percutaneous coronary intervention (PPCI) when possible. Most U.S.-based transfer programs still use complicated protocols that include fibrinolytic therapy often resulting in transfer delays, inappropriately applied therapy (wrong diagnosis) and bleeding and stroke complications. These protocols are often emphasized in low-volume centers. We implemented a program absent fibrinolytic therapy and applied it to a network of 25 participating hospitals over a 100-mile radius in central Minnesota. Methods and Results. One-thousand consecutive patients ages 21 to 90 who presented within 12 hours of the onset of symptoms consistent with MI from April, 2004 to January, 2008 were included in this registry. Prior to transfer to the cardiac catheterization laboratory, patients received aspirin and heparin. Clopidogrel was added to the protocol in January, 2007. Glycoprotein (GP) IIb/IIIa inhibitors were typically utilized after diagnostic catheterization and prior to PPCI. Median door-to-balloon time was 56 minutes at the PCI Center and 110 minutes from referral sites (RS). Of the transfer patients, 71% underwent helicopter transfer. The success rate for PPCI was 99.4%. Despite inherent transfer delays, there was no difference in mortality between the PCI Center and RS. Overall mortality rates in-hospital, at 30 days, at 6 months, and 1 year were 2.1%, 2.9%, 3.8% and 4.5%, respectively, with follow up on 998 of 1,000 patients. In-hospital stroke, reinfarction and major bleeding were 0.7%, 2.0% and 2.7%, respectively. Conclusions. Despite increasing trends toward a pharmacoinvasive approach in transfer patients with STEMI, a protocol which stresses rapid transfer and PPCI results in excellent outcomes, with very low complication rates without fibrinolytic therapy. J INVASIVE CARDIOL 2009;21:639–644 Key words: angioplasty, myocardial infarction, ST elevation To date, ST-elevation myocardial infarction (STEMI) transfer programs in the U.S. stress the use of fibrinolytic therapy despite the excellent results demonstrated in European trials utilizing primary percutaneous coronary intervention (PPCI).1,2 Higher-risk patients may benefit even more from PPCI.3 The American College of Cardiology/American Heart Association (ACC/AHA) guidelines emphasize a reperfusion goal of ≤ 90 minutes. This recommended time frame has likely led to continued fibrinolytic therapy at many transfer sites.4 Several trials show good results when fibrinolytic therapy is used (often) in combination with facilitated or rescue PCI.5–7 Yet, more recent studies show fibrinolytic therapy is associated with bleeding complications and less than thrombolysis in myocardial infarction (TIMI) 3 flow in many patients.2,6 We developed a network of 25 referral hospitals in central Minnesota within a 100-mile radius (Figure 1) for purposes of rapid diagnosis and urgent transfer for PPCI to one centralized PCI center for the treatment of STEMI. From April 2004 to January 2008, 1,000 consecutive patients underwent emergency cardiac catheterization for suspected STEMI. A straightforward protocol excluding fibrinolytic therapy and focused on rapid transfer from a limited distance was devised and followed. Methods Patients who presented within 12 hours of symptoms consistent with MI and also demonstrating ST elevation (STE) were eligible for inclusion in the registry. On-site patients, either from the emergency room (ER), telemetry ward, or coronary care unit, received four 81 mg chewable tablets of aspirin and 5,000 units of intravenous heparin. Laboratory studies were drawn and other treatment was left to the discretion of the ER attending physician or consulting cardiologist. Rapid transfer to the cardiac catheterization laboratory (cath lab) was emphasized. The program was formally initiated on April 1, 2004. At that time, patients presenting to a network of participating hospitals with the same criteria were treated with the same protocol with continued emphasis of rapid transfer. Prior to this date, patients were treated on an ad hoc basis, with physician-to-physician communication and subsequent individualized treatment. With the above protocol, one phone call initiated a cascade of events, facilitating transfer and alerting all involved personnel including the interventional cardiologist and cath lab staff. The program was referred to as “STEMI-SC” and one of the authors (RA) visited 18 of the 25 referral sites (RS) to provide necessary education for involvement in the network. The primary PCI center was the nearest available facility performing PCI for all RS. Data collection to include 6-month follow up of all patients was completed in August 2008, and was provided by the on-site institution (St. Cloud Hospital). There was no sponsorship from any catheter-based or pharmaceutical company. Inclusion/exclusion criteria. Patients with symptoms of MI and STE, suspected new left bundle branch block (LBBB), or electronic pacing were entered into the registry. Patients were not included if they presented > 12 hours into their course or if they were 90 years of age. Patients were also excluded from the registry if they had an advanced illness with a life expectancy of STEMI-SC Protocol Immediately following the ECG diagnosis, typically by an ER physician, a single phone call was made using a dedicated number. The STEMI-SC system was then activated and all appropriate personnel were notified. Helicopter transfer was recommended from all sites, but the mode of transfer was ultimately at the discretion of the referring provider. Phone consultation between the referring MD and the accepting cardiologist was encouraged but optional. On arrival to St. Cloud Hospital, the patient was taken directly to the cath lab and a team consisting of 4 cath lab personnel plus 1 or 2 cardiologists was on hand to assume care. Diagnostic angio-graphy was performed emergently, and when appropriate, PPCI was performed by 1 of 8 interventional cardiologists. St. Cloud Hospital is a 489-bed facility serving as a regional RS for central Minnesota. The Central Minnesota Heart Center at St. Cloud Hospital employs 20 cardiologists and performs more than 8,000 cardiac procedures annually, including 1,200–1,500 PCIs per year. Patients were treated with IV heparin and GP IIb/IIIa inhibitor use was at the discretion of the cardiologist. The use of aspiration devices, stent choice and intra-aortic balloon pump (IABP) was also at the discretion of the operator. Most patients underwent recovery in the coronary care unit following PPCI. All post-PCI care and other general care were provided by the admitting cardiologist. A consulting intensivist was also available for ventilator management and other supportive care. Patients who underwent emergency coronary artery bypass recovered in the intensive care unit. Data were recorded using a dedicated STEMI database and the ACC National Cardiovascular Data Registry. Phone call follow-up for assessment of mortality was coordinated exclusively by one of the authors (CL). This observational study received institutional review board approval from the St. Cloud Hospital. Definitions. All patients with STE or ECG equivalence were included in the study since treatment was initiated based on the admission ECG. Results of those patients who received PPCI are reported separately in addition to the entire patient population. Symptom onset was obtained by patient history, emergency personnel records and information from family members when necessary. Shock was defined as persistent systolic blood pressure 3 gm/dl drop in hemoglobin (included in ACC database information for all PCI and not just PPCI) was not included due to dilutional effects in critically ill patients administered volume. Stroke was defined as a clinically relevant neurologic deficit with or without cerebral imaging. Reinfarction was defined as occlusion of the infarct-related artery intervened on at presentation. Statistical analysis. Continuous time variables are summarized as the median, with lower quartile and upper quartile. Other continuous variables are summarized with the mean ± standard deviation. Discrete variables are presented as frequency (percentage). Differences between the St. Cloud PCI Center and the RS are tested using Mann-Whitney-Wilcoxon (for time variables), two-sample t-tests (for other continuous variables) and the Pearson chi-square (for discrete variables). Not all patients in the database underwent PPCI. Statistical analyses were performed using SAS version 9.1, SPSS version 16.0, and Minitab version 15. Results Patient characteristics. Baseline patient characteristics for St. Cloud Hospital patients (PCI Center) and RS are shown in Table 1. Nearly 3 of every 4 patients are transferred to the PCI Center. Patients from RS tended to be older. The incidence of dyslipidemia and the incidence of prior MI or PCI were higher in the local population. Shock was relatively rare in both groups, likely due to the very strict definition. Flow of patients. Figure 2 shows the flow of patients presenting with presumed STE within the stated time course. Thirty five patients presented at > 12 hours into their MI. Twenty five patients had no evidence of STE or new LBBB, and though most underwent coronary angiography, these patients were excluded from the registry. Only 9 patients were excluded due to severe underlying illness and a life expectancy of Discussion Multiple studies have shown a mortality benefit in STEMI patients treated with PPCI (especially in the most critically ill) who are revascularized in a timely manner.1–3,5–11 The benefit of PPCI in treating STEMI has led to the development of transfer programs in the United States. Many programs have extended their RS to over 150 miles, or have organized multiple PCI centers of care on a regional basis.5–8 Most of these programs use a pharmacoinvasive strategy including half-dose or full-dose fibrinolytic therapy. Difficulties in diagnosing STEMI at referring sites and subsequent complicated protocols can lead to prolonged transfer times and inappropriate use of fibrinolytic therapy.12 In an attempt to maximize patient benefit with PPCI, our program is limited to a radius of 100 miles and excludes the use of fibrinolytic therapy for both on site and transfer patients while emphasizing rapid transfer. This straightforward approach was developed with smaller RS in mind. Many of the rural hospitals in our network treat 5 or fewer STEMI patients per year (Figure 4). The use of fibrinolytic therapy is often ineffective and can be complicated due to logistical difficulties in adhering to national ACC/AHA recommendations for timeliness to reperfusion.4 Multiple trials of fibrinolytic therapy over several decades demonstrate TIMI 3 flow at 90-minute angiography in only about 30–60% of treated patients.13,14 In the PRAGUE study, the arm which included 100 patients receiving both full-dose fibrinolytic therapy and PCI achieved only 30% TIMI 3 flow at the time of angio-graphy.2 Even with more advanced fibrinolytic agents, reperfusion is suboptimal. A 40 mg dose of tenecteplase results in TIMI 3 flow only 63% of the time at 90 minutes.15–17 Furthermore, when patients receive fibrinolytic therapy, they must be assessed for successful reperfusion if immediate angiography is not used. Unfortunately, clinical markers to assess reperfusion are insensitive in determining the need for rescue PCI.18 In MERLIN, 53% of patients without chest pain had 90 minutes prior to PPCI may lead to less than optimal results.22–26 As a result, fibrinolytic therapy has been proposed as the preferred STEMI management strategy for transfer patients if anticipated D2B times exceed 90 minutes.27 Despite implementing methods to reduce D2B times,28–33 inherent delays have led to the continued use of fibrinolytic agents at many transfer sites. However, a prior meta-analysis of 3,750 patients has shown overall superiority with PPCI in combined endpoints over fibrinolytic therapy, even when transport time is up to 3 hours.34 Dalby et al showed a 42% reduction in death, reinfarction and stroke in patients treated with PPCI despite 5 of the 16 centers having prolonged median D2B times. Similarly, with our protocol, despite > 120-minute D2B times for 40% of the patients, survival rates were excellent, and there was no statistical difference from those treated more quickly (Figure 5). Though it would be desirable to improve transfer times from many sites, these encouraging results may be due, in part, to TIMI 2 or 3 flow in 31.1% of transferred patients on initial angiography. Accruing data of facilitated PCI (not including fibrinolytic therapy) and PPCI mirror our results. The recently reported Horizons-AMI trial of 3,602 patients showed an identical 2.6% mortality rate at 30 days in both on-site and transfer patients despite longer D2B times in the transfer patients (mean 134 vs. 87 minutes; p 90 minutes, however, 1-year mortality rates were statistically the same (~8.0%) as those treated within 90 minutes.36 Study limitations. As discussed, multiple studies involving PPCI have been published. Our registry reflects “real-world” results that closely mirror the results of the multicenter HORIZONS-AMI trial and reflect true PPCI similar to the PRAGUE, DANAMI and AIR PAMI trials. The results are excellent and could be seen as such due to selection bias. Yet, exclusions from the protocol were few. After accounting for patients without ST changes and patients who presented > 12 hours and the elderly (total = 64), only 22 patients were excluded (2.2%) for reasons of prolonged resuscitation or Conclusions Despite current trends toward a pharmacoinvasive strategy of reperfusion for STEMI transfer programs, our large, single-center registry demonstrates excellent survival rates and low morbidity in the treatment of both transfer and on-site STEMI patients. By following a PPCI protocol which does not include fibrinolytic therapy, diagnosis-specific treatment is utilized in all patients. 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