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.
PHARMACOINVASIVE STRATEGY: GOOD RESULTS IN HIGH-RISK PATIENTS
A number of randomized studies during the last 10 years have examined the value of a pharmacoinvasive strategy.15,16,26–29
The TRANSFER-AMI trial
The TRANSFER-AMI trial15 randomized 1,059 patients with high-risk ST-elevation MI (ie, anterior or high-risk inferior) at non-PCI centers to undergo either pharmacoinvasive care, ie, full-dose tenecteplase (TNKase) with immediate transfer for PCI or standard care, ie, tenecteplase with transfer for rescue PCI if the patient had persistent ST-segment elevation, chest pain, or hemodynamic instability.15 The goal was to perform PCI within 6 hours of thrombolysis, and the median time to PCI was 3.9 hours (range 2–6 hours). In the standard-care group, 35% of patients needed to be transferred for rescue PCI. Unlike in the ASSENT-4 trial, over 80% of patients received aggressive antiplatelet therapy with both 300 mg of clopidogrel and glycoprotein IIb/IIIa inhibitors.
The rate of cardiovascular events at 30 days was significantly lower with pharmacoinvasive therapy than with standard care and rescue PCI (11% vs 17%, P = .004). This difference was driven by lower rates of recurrent ischemia, reinfarction, and heart failure.
The CARESS-in-AMI study
The CARESS-in-AMI study16 found a similar improvement in ischemic outcomes in 600 patients with high-risk ST-elevation MI arriving at non-PCI centers if they had received pharmacoinvasive therapy. Patients received half-dose reteplase and abciximab and were randomized either to be immediately transferred for PCI (median time to PCI 2.25 hours) or to be transferred only if they had persistent ST-segment elevation or clinical deterioration.16 The event rate was low with pharmacoinvasive therapy, comparable to that achieved in primary PCI trials.
Interestingly, no significant increase was seen in the risk of major and minor bleeding in these two trials despite the use of a femoral approach for PCI in over 80% of the cases; this is probably due to the delays between thrombolytic administration and PCI and to the use of a highly fibrin-specific thrombolytic agent and adjusted-dose heparin.
Meta-analysis of pharmacoinvasive trials
A meta-analysis29 of studies of systematic early PCI (mainly with stenting) within 24 hours of thrombolysis showed a reduction in the rates of mortality and reinfarction with this strategy, without an increase in the risk of major or intracranial bleeding.30 In contrast to the results of the trials of facilitated PCI, a pharmacoinvasive strategy improved outcomes in these trials because the delay between thrombolysis and PCI was more than 2 hours, ie, long enough to prevent bleeding complications, and because most patients randomized in these trials presented within 2 to 3 hours of symptom onset, when the time to reperfusion is critical. After 3 hours, the PCI-mediated myocardial salvage is less time-dependent. Moreover, trials of pharmacoinvasive strategy used aggressive antiplatelet therapy with clopidogrel and glycoprotein IIb/IIIa inhibitors.
Comment: Pharmacoinvasive strategy in the guidelines
These results and those of the subgroup analysis from the FINESSE trial suggest that patients with high-risk ST-elevation MI treated at non-PCI hospitals have better outcomes without an increase in major bleeding events when given thrombolysis and then immediately transferred for routine PCI, rather than being transferred only if reperfusion fails.
Hence, the 2009 update of the ACC/AHA guidelines31 gives a class IIa recommendation for transferring patients with anterior ST-elevation MI or high-risk inferior ST-elevation MI treated with thrombolysis to a PCI-capable facility where PCI is performed as part of a pharmacoinvasive or rescue strategy soon after thrombolysis.
This strategy has been particularly studied in patients younger than 75 years presenting with high-risk types of ST-elevation MI early (< 3 hours) after symptom onset. If not at high risk, the patient may be transferred to a PCI facility after receiving thrombolysis or observed in the initial facility (class IIb recommendation). Consideration should be given to starting anticoagulant and antiplatelet therapy before and during transfer—ie, 300 mg of clopidogrel before transfer for PCI and glycoprotein IIb/IIIa inhibitor therapy during PCI.
The European Society of Cardiology (ESC) guidelines32 recommend early routine angiography 3 to 24 hours after successful thrombolysis. This time window was selected to avoid PCI during the prothrombotic period in the first few hours after thrombolysis and to minimize the risk of reocclusion with PCI delays of more than 24 hours (class IIa recommendation).
Larger randomized trials are still needed to establish whether the pharmacoinvasive strategy confers a survival benefit, to determine its usefulness in low-risk inferior or lateral ST-elevation MI, and to further refine the time window when PCI is both safe and beneficial after thrombolysis.33
RESCUE PCI REDUCES MORTALITY RATES
Rescue PCI is the most accepted form of thrombolysis-PCI combination.
The REACT trial
The REACT trial20 showed that rescue PCI performed at a mean of 4.5 hours after failed thrombolysis reduces the rate of adverse cardiovascular events by more than 50% at 6 to 12 months and reduces the 5-year mortality rate by more than 50% compared with conservative management.20 As in the pharmacoinvasive strategy, aggressive antiplatelet regimens were used in the REACT trial.
A meta-analysis of rescue PCI trials
A meta-analysis of rescue PCI trials34 confirmed these results, showing a reduction in heart failure and reinfarction and a trend toward a lower mortality rate with rescue PCI.34 After thrombolysis, 40% of patients do not achieve grade 3 TIMI flow, which explains why in modern clinical trials 30% of patients treated with thrombolysis require rescue PCI.5,15,16,35
For patients with high-risk ST-elevation MI, current ACC/AHA guidelines assign a class IIa recommendation to rescue PCI.31
