Combined reperfusion strategies in ST-segment elevation MI: Rationale and current role
ABSTRACTPrimary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST-elevation myocardial infarction (MI), but most patients do not arrive at a PCI facility within the recommended 90 minutes of first medical contact. If delay is expected, timely thrombolysis is recommended, followed by early transfer for PCI. The authors review the rationale behind three combined reperfusion strategies—facilitated PCI, pharmacoinvasive therapy, and rescue PCI—and data on their effectiveness.
KEY POINTS
- When the expected door-to-balloon time is less than 90 minutes and the door-to-balloon time minus the door-to-needle time is less than 60 minutes, the preferred approach is PCI not preceded by thrombolysis.
- Evidence suggests that routine early (but not immediate) PCI—ie, 2 to 6 hours after thrombolysis—is beneficial, particularly in patients with high-risk ST-elevation MI.
- Hospitals and emergency services should participate in community-based and regional systems of care, with standardized protocols to ensure expeditious transfer and prompt reperfusion.
- Prehospital thrombolysis followed by early transfer to a PCI facility as part of a community-based system of care may further improve outcomes of patients with very long transfer times.
Effective and rapid reperfusion is crucial in patients with acute ST-segment elevation myocardial infarction (MI). The preferred strategy for reperfusion—when it can be performed in a timely fashion at an experienced facility—is primary percutaneous coronary intervention (PCI), which produces outcomes superior to those of pharmacologic thrombolysis.1
Unfortunately, in the United States about half of patients present to hospitals that do not have PCI capability,2 and in one analysis, 91% of transferred patients had a door-to-balloon time greater than the recommended 90 minutes, with a mean of 152 minutes.3 (In this case, the door-to-balloon time was the time that elapsed between entry into the first hospital and inflation of the PCI balloon at the second hospital.)
In situations such as these, a combined approach may be appropriate, with thrombolysis delivered by paramedics or at a local facility, followed by transfer to a PCI facility and performance of PCI within a few hours. However, this is feasible only if standardized community-based or regional protocols for prompt transfer and reperfusion are in place.
In this paper we discuss the rationale and the clinical data behind several approaches to combined reperfusion, as well as experiences with community-based care protocols.
WITHIN 3 HOURS OF SYMPTOM ONSET, THROMBOLYSIS IS AS GOOD AS PCI
The PRAGUE-2 Trial
In the randomized PRAGUE-2 trial,4 patients with ST-elevation MI who presented to a non-PCI facility had better outcomes if they were transferred promptly for PCI (median door-to-balloon time 97 minutes), as opposed to receiving local therapy with streptokinase. However, for patients presenting within 3 hours of symptom onset, the mortality rates were comparable with either strategy.4
See the glossary of clinical trial names below
The CAPTIM trial
In the CAPTIM trial,5 patients who presented within 2 hours of symptom onset and who were randomized to receive prehospital thrombolysis had outcomes similar to those of patients treated with primary PCI, despite a short door-to-balloon time (82 minutes).
The Vienna STEMI Registry
In the Vienna STEMI Registry,6 the mortality rates with primary PCI and with thrombolysis were similar when patients presented within 2 hours of symptom onset. However, as the time from symptom onset increased, primary PCI appeared to offer an increasing survival benefit compared with thrombolysis.
Comments: Thrombolysis is effective mostly in the first 2 to 3 hours, with some benefit up to 12 hours
Previous studies have shown that the sooner thrombolysis is given after symptom onset, the more effective it is. If it is given within an hour of symptom onset, the relative reduction in the mortality rate is 50% and the absolute reduction is 6.5% compared with no reperfusion therapy. If it is started in the second hour, the absolute reduction in the mortality rate drops to 4%, and a lesser benefit extends to patients presenting up to 12 hours after symptom onset.7 This time-dependent benefit is due to the fact that very early reperfusion of the occluded coronary artery may lead to full recovery of ischemic tissue and thus prevent necrosis. In addition, thrombolysis in the first 2 hours is highly efficacious in lysing a fresh thrombus.
These data support the current guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA), which state no preference for either thrombolytic therapy or PCI in ST-elevation MI if the presentation is less than 3 hours after symptom onset.8
Of note, in the CAPTIM trial and in the Vienna STEMI Registry, rescue PCI was available and was in fact used after thrombolysis in about 25% of patients, which might have contributed to the benefit of early thrombolysis.
PRIMARY PCI MAY NOT BE SUPERIOR IF TRANSFER TIME IS LONG
Another time-related factor to consider is the PCI-related delay, ie, the theoretical difference between the expected time from first medical contact to balloon inflation (if the patient undergoes primary PCI) and the time from first medical contact to the start of thrombolytic therapy (if the patient undergoes primary thrombolysis).
A meta-analysis of 13 trials comparing PCI and thrombolysis showed that a PCI-related delay of more than 60 minutes might negate the potential advantage of primary PCI over immediate thrombolysis in terms of deaths.9
This observation has been further refined by data from the National Registry of Myocardial Infarction.10 In this analysis, patient factors, including age, duration of symptoms, and infarct location, significantly affected the point at which the PCI-related delay negated the survival advantage of primary PCI. The survival advantage of primary PCI was lost more rapidly—with a PCI-related delay as short as 40 minutes—in patients who presented sooner, were younger, or had anterior MI. Primary PCI maintained its survival advantage even with a PCI-related delay longer than 100 minutes in older patients or patients with nonanterior MI presenting more than 3 hours after symptom onset. Given that median door-to-balloon times in the United States may exceed 150 minutes when transfer is involved, 3 primary PCI may be no better than primary thrombolysis in transferred patients who present early or who have large infarcts.
Although these results were derived from a post hoc analysis of a registry and the delay times reported were sometimes inaccurate, they suggest that both the PCI-related delay time and patient characteristics should be considered when selecting a reperfusion strategy. Thrombolytic therapy before and in conjunction with primary PCI was considered a potential solution to these concerns.
In addition, while the benefit of any reperfusion strategy depends on the time of presentation, the loss in benefit by later presentation is less pronounced with primary PCI than with thrombolysis, making thrombolysis less attractive in later presentations (> 3 hours).11
Also, while thrombolytic therapy in patients older than 75 years was associated with a lower mortality rate compared with no therapy in a large Swedish registry,12 this benefit was less striking than in younger patients. A meta-analysis of thrombolysis trials failed to show a similar benefit in patients over age 75 vs younger patients,13 whereas primary PCI remained effective and superior to thrombolysis in the elderly, with more absolute reduction in mortality rates in the elderly subgroup than with younger patients. 14 This makes thrombolysis less attractive in the elderly, either as a stand-alone therapy or in conjunction with PCI. Studies of combined thrombolysis and PCI included very few patients over age 75.15–17
