VIEWPOINT AND COMMENTARY
Is There Any Time Left for Primary Percutaneous Coronary Intervention According to the 2007 Updated American College of Cardiology/American Heart Association ST-Segment Elevation Myocardial Infarction Guidelines and the D2B Alliance?
Christian J. Terkelsen, MD, PhD*,
Jacob T. Sørensen, MD and
Torsten T. Nielsen, MD, DMSc
Department of Cardiology B, Aarhus University Hospital, Aarhus, Denmark
Manuscript received March 26, 2008;
revised manuscript received May 13, 2008,
accepted May 19, 2008.
* Reprint requests and correspondence: Dr. Christian J. Terkelsen, Department of Cardiology B, Aarhus University Hospital, DK-8200 Aarhus N, Denmark (Email: Christian_Juhl_Terkelsen{at}hotmail.com).
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Abstract
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Early reperfusion therapy is essential in the treatment of patients with ST-segment elevation myocardial infarction. Fibrinolytic therapy is a feasible reperfusion strategy to be initiated at any hospital and preferably in the pre-hospital phase. Primary percutaneous coronary intervention (PPCI) is acknowledged as a superior reperfusion strategy when initiated in a timely fashion. It is also the preferred reperfusion therapy in patients who exhibit cardiogenic shock and in patients with contraindications to fibrinolysis. However, in many regions, it is difficult to establish a successful PPCI strategy because it mandates optimal pre-hospital and in-hospital triage to ensure acceptable treatment delays. The 2007 updated American College of Cardiology/American Heart Association ST-Segment Elevation Myocardial Infarction Guidelines stress that "the focus for PPCI is from first medical contact because in regionalization strategies, extra time may be taken to transport patients to a center that performs the procedure" and that "time from Emergency Medical Services arrival to balloon inflation should be <90 minutes." When considering fibrinolysis, however, the guidelines accept a door-to-needle time of 30 min from arrival at the local hospital. Is there evidence to justify that, in the PPCI setting, the clock starts ticking upon the arrival of the Emergency Medical Services but, in the setting of in-hospital fibrinolysis, it does not start until a patient's arrival at the local hospital?
Key Words: myocardial infarction • primary percutaneous coronary intervention • percutaneous coronary intervention-related delay • fibrinolysis • guidelines
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Abbreviations and Acronyms
| | D2B = door-to-balloon | | EMS = Emergency Medical Services | | PCI-related delay = extra treatment delay when performing primary percutaneous coronary intervention instead of fibrinolysis | | PPCI = primary percutaneous coronary intervention | | STEMI = ST-segment elevation myocardial infarction |
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Transfer Patients
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If we consider patients with ST-segment elevation myocardial infarction (STEMI) living in the catchment area of a non-percutaneous coronary intervention (PCI)-capable hospital who are transported by an Emergency Medical Services (EMS) provider without the capability of initiating pre-hospital fibrinolysis, the pre-hospital delay typically includes a 10-min delay on scene and a 10-min transportation delay to the local hospital. After arrival at the hospital, a 30 min door-to-needle time is acceptable, according to the guidelines (1), which translates into an acceptable EMS arrival to needle time of 50 min (Fig. 1A).
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Figure 1 Typical Treatment Delays According to Reperfusion Strategy
Typical treatment delays when considering: (A) in-hospital fibrinolysis, (B) interhospital transfer for primary percutaneous coronary intervention (PPCI), (C) pre-hospital rerouting to the catheterization laboratory at a high-volume percutaneous coronary intervention (PCI) center, and (D) admission at a local low-volume PCI center. For the various "PCI-related delays," the acceptable transport time is presented for patients rerouted to a PCI center pre-hospital. ACC/AHA STEMI Guidelines = American College of Cardiology/American Heart Association ST-Segment Elevation Myocardial Infarction Guidelines; EMS = Emergency Medical Services.
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When considering the alternative (i.e., transfer to a PCI-capable hospital), the updated guidelines (1) only accept an EMS arrival-to-balloon time of 90 min, which translates into an acceptable extra delay when performing primary percutaneous coronary intervention (PPCI) instead of fibrinolysis of only 40 min (the so-called PCI-related delay). A maximal acceptable PCI-related delay of 40 min renders no patients eligible for transfer to PPCI if the door-to-balloon (D2B) time at the interventional hospital is 90 min (Fig. 1B). Even an in-the-door/out-the-door delay of only 30 min at the local hospital combined with an interhospital transfer time of only 10 min would mandate a D2B time of 30 min or less (Fig. 1B). The acceptable EMS arrival-to-balloon time clearly varies from region to region and is dependent on the alternative reperfusion therapy available (pre-hospital fibrinolysis or in-hospital fibrinolysis) and on the acceptable PCI-related delay.
There is an ongoing controversy regarding the acceptable PCI-related delay. However, this is the first time that a PCI-related delay of only 40 min is considered. Nallamothu et al. (2,3) initially recommended a maximum PCI-related delay of 60 min based on a regression analysis performed on tabulated data from previous randomized controlled trials comparing fibrinolysis with PPCI. This recommendation also was included in the 2004 American College of Cardiology/American Heart Association (ACC/AHA) STEMI guidelines (4). The Nallamothu regression analysis was hampered by their underestimation of the PCI-related delays from several of the trials included. When the regression analysis based on the original tabulated data is recalculated, the acceptable PCI-related delay becomes 120 min (5,6). Still, these "back-of-the envelope" regression analyses have been based on only 21 (2) and 22 (5) values of the association between mortality and PCI-related delay; for example, in the regression analyses each trial was represented by 1 value only.
However, in multicenter trials, PCI-related delay can be calculated at center level. Boersma et al. (7) performed a more optimal regression analysis based on almost the same trials as the Nallamothu et al. (2) regression analysis, but they implemented data on PCI-related delay at the center level (i.e., 153 values for the association between mortality and PCI-related delay). The Boersma et al. (7) meta-analysis found that PPCI was superior to fibrinolysis even at PCI-related delays of 80 to 120 min (Fig. 2). Some have argued that the trials included in the Boersma et al. (7) meta-analysis were obsolete because the fibrinolytic therapy was not optimal. However, 70% of fibrinolytic-treated patients were given fibrin-specific drugs, whereas only 30% to 40% of PPCI-treated patients were managed optimally with stents and glycoprotein IIb/IIIa inhibitors (7,8). Thus, both reperfusion strategies were below the standard of today, but there is no particular reason to believe that the mortality benefit achieved by an optimal fibrinolytic therapy is greater than the benefit achieved when introducing stents and glycoprotein IIb/IIIa inhibitors.
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Figure 2 ORs for 30-Day Death in Patients Randomized to PPCI Compared With Fibrinolysis
Odds ratio (OR) and 95% confidence interval (CI) for 30-day death in patients randomized to primary percutaneous coronary intervention (PPCI) when compared with fibrinolysis (FL) according to presentation delay (left) and PCI-related delay (extra delay used to perform PPCI instead of initiating fibrinolysis) (right). Odds ratios were adjusted for patient-, hospital-, and study-level covariates. From Boersma et al. (7).
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Pinto et al. (9) also studied the PCI-related delay based on the NRMI (National Registry of Myocardial Infarction) registry data. They found that infarct location, age, and treatment delay may have an impact on PCI-related delay. Overall, PPCI was superior to fibrinolysis up to a PCI-related delay of 114 min (9). Any analysis based on the NRMI registry, however, should take into account that: 1) the NRMI registry is based on voluntarily reported cases and therefore potentially is hampered by selection bias; 2) the NRMI registry has a greater proportion of patients in cardiogenic shock and with anterior myocardial infarction in the PPCI-treated group (10) (e.g., high-risk patients selected for PPCI), which results in an underestimation of the maximal acceptable PCI-related delay; 3) in the NRMI registry, fibrinolytic-treated patients were given fibrin-specific drugs in 92% of cases (9), but PPCI-treated patients were treated at low-volume centers performing only 21 PPCIs/year in mean (9); 4) there are no published data on the use of stents and glycoprotein IIb/IIIa inhibitors in the PPCI-treated group; and 5) PPCI-treated patients had D2B times of 116 min in mean (9).
Low-volume PPCI centers often are established to allow easy geographical access to the PPCI centers. This, however, is not necessarily associated with short treatment delays (Fig. 1D). Thus, in the NRMI registry, PCI centers with a PCI-related delay <60 min and a D2B time of 91 min had a yearly PPCI volume of 24, whereas centers with a PCI-related delay >120 min and a D2B time of 179 min had a yearly PPCI volume of 11 (9). An alternative strategy is to establish more remote high-volume PCI centers. A high volume of PPCIs to ensure daily activation of the system (300 to 400 PPCIs/year) and a sufficient number of PCI operators to perform on a 24 h/day 7 days/week basis should guarantee that the catheterization laboratory can be activated promptly. This suggestion is supported by the observation that centers performing 500 to 700 PPCIs/year consistently report D2B times of 30 min or less (11,12). These short D2B times translate into a longer acceptable transport time, allowing a larger catchment area (Fig. 1C).
A consensus is needed regarding the maximum acceptable PCI-related delay which will allow us to determine the acceptable transfer time/transport time to PCI-capable hospitals when considering PPCI instead of fibrinolysis. There is so far no evidence to support a maximum acceptable PCI-related delay of only 40 min in patients living in the catchment area of non–PCI-capable hospitals as indicated by the 2007 Focused Update of the ACC/AHA STEMI Guidelines (1).
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Nontransfer Patients
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When focusing on patients living in the catchment area of a PCI-capable hospital, the updated STEMI guidelines recommend an EMS arrival-to-balloon time of less than 90 min. Again, if considering a 10-min on-scene delay and 10-min transportation delay this translates into an acceptable D2B time of 70 min (Fig. 1D) (1). Nevertheless, a 90-min acceptable D2B time has been adapted by the D2B Alliance, which recently was established with the purpose of "achieving a D2B time of  90 minutes for at least 75% of nontransfer PPCI patients with STEMI in all participating hospitals performing PPCI." In this initial phase, the D2B Alliance have primarily focused on in-hospital strategies to reduce D2B time and, in their "Summary of Evidence Review," excluded studies focusing on reducing D2B times in transfer patients and studies focusing on the benefit of pre-hospital rerouting of patients directly to catheterization laboratories for PPCI (13). Given that the majority of patients with STEMI are living in the catchment area of non–PCI-capable hospitals and the fact that numerous studies have documented a substantial reduction in treatment delay achieved by pre-hospital diagnosis and rerouting of patients with STEMI directly to PCI centers/catheterization laboratories (14–17), the D2B Alliance may consider expanding their core strategies and implement out-of-hospital initiatives. Thus, an extended set of core strategies has been implemented in regions that have successfully reduced treatment delay in STEMI patients (Table 1) (i.e., focusing on pre-hospital diagnosis and pre-hospital rerouting directly to catheterization laboratories running 24 h/day 7 days/week and bypassing local hospitals as well as intensive care units, the coronary care units, and emergency departments at the interventional hospital).
To monitor initiatives aimed at reducing both pre-hospital and in-hospital delay in the initiation of reperfusion therapy, we would recommend that the D2B Alliance consider implementing "system delay" as an effect parameter, that is, "delay from EMS call to initiation of reperfusion therapy" (5,6). "System delay" comprises all the elements of treatment delay eligible for reduction by the health care personnel: 1) EMS response time; 2) on-scene delay; 3) transportation delay to the local hospital (if not bypassed); 4) in-the-door/out-the-door delay at the local hospital; 5) transfer time to the PCI-capable hospital; and 6) D2B time at the PCI-capable hospital.
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Conclusions
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We would recommend that the committee responsible for the updated ACC/AHA guidelines for future revisions consider extending the acceptable PCI-related delay to 90 or 120 min according to the present evidence. Instead of focusing on D2B delay, we would also recommend that the D2B Alliance focus on initiatives that will reduce "system delay" in PPCI patients, for example, pre-hospital diagnosis, pre-hospital rerouting of STEMI patients directly to PPCI-centers, pre-hospital activation of the catheterization laboratory, and establishment of large-volume PCI centers running 24 h/day 7 days/week to ensure a D2B time of 30 min or less. This suggestion would clearly expand the catchment areas of the PCI-capable hospitals and potentially make PPCI a feasible reperfusion strategy in the majority of patients with STEMI.
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References
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Abstract
Transfer Patients