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.
THREE COMBINATION REPERFUSION STRATEGIES
Facilitated PCI is a strategy of thrombolysis immediately followed by PCI, with a planned door-to-balloon time of 90 to 120 minutes.
Pharmacoinvasive therapy means giving thrombolysis at a non-PCI facility and then promptly and systematically transferring the patient to a PCI facility, where PCI is performed 2 to 24 hours after the start of thrombolytic therapy, regardless of whether thrombolysis results in successful reperfusion. 15 Thus, the time to PCI is longer than with facilitated PCI. Facilitated PCI addresses the value of pretreatment with thrombolytics or glycoprotein IIb/IIIa inhibitors in patients otherwise eligible for primary PCI, whereas pharmacoinvasive therapy addresses the value of routine early PCI after thrombolysis in patients who are not eligible for primary PCI.16
Rescue PCI refers to PCI that is performed urgently if thrombolysis fails, failure being defined as persistent hemodynamic or electrical instability, persistent ischemic symptoms, or failure to achieve at least a 50% to 70% resolution of the maximal ST-segment elevation 90 minutes after the infusion is started.
FACILITATED PCI: NEGATIVE RESULTS IN CLINICAL TRIALS
ASSENT-4 PCI trial
In the ASSENT-4 PCI trial,18 patients receiving full thrombolytic therapy before PCI had a higher rate of in-hospital death, bleeding, and cardiovascular events at 90 days than patients treated with primary PCI.
This trial recruited patients arriving at hospitals with or without PCI capability. The door-to-balloon time was about 110 minutes in both groups, which might not have been prolonged enough to show a benefit from a timely addition of thrombolysis. In addition, antiplatelet therapy was limited in these patients: glycoprotein IIb/IIIa inhibitors were not given, and clopidogrel (Plavix) was not appropriately preloaded, and this might have offset the potential benefit of early PCI. In fact, data suggest that platelet activation and aggregation are heightened after thrombolysis, 21–23 and that glycoprotein IIb/IIIa antagonists can inhibit these effects.23
The FINESSE trial
In the FINESSE trial,19 patients were randomized to undergo primary PCI, to undergo PCI facilitated (ie, preceded) by abciximab (Reo-Pro), or to undergo PCI facilitated by half-dose reteplase (Retavase) and full-dose abciximab. Despite a median door-to-balloon time of 132 minutes, the three strategies were associated with similar rates of death, heart failure, or ischemic outcome at 90 days. Even though the dosage of heparin was weight-adjusted, more major bleeding events occurred with the facilitated strategies.
Comments: Some subgroups may still benefit from facilitated PCI
The results of ASSENT-4 PCI and FINESSE led to the conclusion that PCI facilitated by full-dose thrombolysis should be avoided, and called into question the value of PCI facilitation using glycoprotein IIb/IIIa inhibitors with or without half-dose thrombolytic therapy.
However, subgroup analyses of these trials identified some subgroups that may benefit from a facilitated strategy. In ASSENT-4 PCI, 45% of patients were enrolled at PCI hospitals with a minimal PCI-related delay time. These patients had the worst outcome with the facilitated strategy. In contrast, patients who had a short time from pain onset to thrombolysis (2 to 3 hours) and who were given prehospital thrombolysis had a trend toward better outcomes with facilitated PCI.24 And in FINESSE, 60% of patients were enrolled at centers with PCI capability. Analysis of a small subgroup of patients with a Thrombolysis in Myocardial Infarction study (TIMI) risk score of 3 or greater presenting to non-PCI hospitals within 4 hours of symptom onset suggested a potential reduction of ischemic events with the facilitated strategy in these patients.25
Thus, for patients seen in the first 2 to 3 hours after symptom onset, immediate thrombolysis is recommended if PCI will likely be delayed, with or without plans for subsequent early PCI. “Time is muscle,” especially during the first 3 hours.
