Combined reperfusion strategies in ST-segment elevation MI: Rationale and current role

WHEN PATIENTS WITH ST-ELEVATION MI PRESENT TO A NON-PCI HOSPITAL

Transfer for primary PCI vs thrombolysis at the non-PCI hospital

The DANAMI-2 trial³⁶ found that immediate transfer for PCI was superior to onsite thrombolytic therapy, as measured by a reduction in the rate of ischemic events (composite of death, myocardial infarction, or stroke at 30 days): 8.5% vs 14.2% (P < .001). There were no deaths during transfer.³

The PRAGUE-2 trial⁴ showed similar results for patients presenting 3 to 12 hours after symptom onset (30-day mortality rate 6% with immediate transfer vs 15.3% with on-site thrombolysis, P < .002), whereas patients presenting within 3 hours of symptom onset had a similar mortality rate with either therapy.⁴

Comment. These trials showed that transfer for primary PCI is superior to thrombolytic therapy when performed in a timely fashion. However, they were done in countries with established transfer networks and short distances between community hospitals and PCI centers, with a PCI-related delay of only 44 minutes and a door-to-balloon time of 90 minutes despite transfer. The large-scale application of this prompt transfer policy is not practical in most regions in the United States. Thus, a strategy of local thrombolysis followed by routine early transfer for routine or rescue PCI seems warranted when the door-to-balloon time or the PCI-related delay time is expected to be too long.

Experiences with community-based systems of care and prehospital thrombolysis

In Minnesota, Henry et al³⁷ developed a PCI-based treatment system and an integrated transfer program for ST-elevation MI involving 30 hospitals within 210 miles of the Minneapolis Heart Institute. Participating hospitals were divided into two zones: zone 1 hospitals were within 60 miles, and zone 2 facilities were between 60 and 210 miles from the Heart Institute. Zone 2 patients received half-dose tenecteplase (if thrombolytic therapy was not contraindicated) in anticipation of a lengthy transfer time.

The median door-to-balloon time for zone 1 patients was 95 minutes (interquartile range 82 and 116 minutes) and for zone 2 patients 120 minutes (interquartile range 100 and 145 minutes). The diagnosis of ST-elevation MI was made by the emergency department physician, who activated the system with a phone call. The patient was then directly transferred to the catheterization laboratory, most often by helicopter.

The in-hospital death rate for patients who presented to the PCI center and for patients in zones 1 and 2 was similarly low (about 5%).³⁷

In France, the FAST-MI registry,¹⁷ which collected outcome data for different reperfusion strategies, found that thrombolysis yielded in-hospital and midterm results that were comparable to those of primary PCI. Of note, thrombolysis was started early after symptom onset (about 2 hours), and was started in the ambulance in two-thirds of cases. Nearly all patients underwent a pharmacoinvasive strategy that combined thrombolysis with coronary angiography and PCI within 24 hours of symptom onset. These findings suggest that timely thrombolysis followed by semiurgent transfer for PCI is an alternative to primary PCI for patients presenting to hospitals with no PCI capability, and that this alternative offers similar benefit to that of primary PCI.

Five centers in the United States have reported their experience with half-dose thrombolysis in the prehospital setting (in the field or during transfer) or at a non-PCI hospital, followed by prompt transfer to a PCI facility. In this registry of almost 3,000 patients,³⁸ patients treated with thrombolysis had better outcomes than patients directly transferred for primary PCI, with a significantly lower 30-day mortality rate (3.8% vs from 6.4%), and no increase in bleeding.^38,39 The mean door-to-balloon time was long (168 minutes in the primary PCI group and 196 minutes in the thrombolysis-PCI group), which might explain the benefit achieved with prompt thrombolysis.

CARDIOGENIC SHOCK

Patients presenting with left ventricular cardiogenic shock derive a large mortality benefit from revascularization, whether they are transferred or directly admitted to a PCI center. ⁴⁰ Moreover, in the SHOCK registry, patients with predominant right ventricular cardiogenic shock had an in-hospital mortality rate similar to that of patients with predominant left ventricular cardiogenic shock, and revascularization (PCI or surgical revascularization) was associated with a strikingly lower mortality rate in both groups.⁴¹

Thus, all patients with left or right cardiogenic shock should be revascularized on an emergency basis, either surgically or percutaneously.

While trials of pharmacoinvasive therapy excluded patients with cardiogenic shock,^15,16 thrombolytic therapy was associated with improved outcomes in the drug-therapy group of the SHOCK trial and in hypotensive patients randomized in the early thrombolysis trials.¹³ Thus, the ACC/AHA guidelines recommend thrombolytic therapy before transfer if a patient presents in shock within 3 to 6 hours of onset of the MI and delays in transport and intervention are anticipated.⁸

PUTTING IT ALL TOGETHER: MANAGEMENT STRATEGIES

If an effective transfer system is in place, primary PCI not preceded by thrombolytic therapy or glycoprotein IIb/IIIa inhibitor therapy is the preferred approach, according to ACC/AHA and ESC guidelines.^31,32 Giving thrombolytics immediately before PCI is harmful and thus should be avoided when the expected door-to-balloon time is 90 minutes or less.

All hospitals (whether or not they offer PCI) and regional emergency medical services should participate in a community-based system of care for ST-elevation MI, with protocols for expeditious transfer as defined and coordinated by the American Heart Association initiative “Mission: Lifeline.” In addition, a system of field triage and direct transport to the catheterization laboratory of a PCI facility after field activation significantly reduces door-to-balloon times and improves outcomes.⁴²

If such a system is not in place, then a pharmacoinvasive strategy seems best: ie, local full-dose thrombolysis (if not contraindicated) followed by transfer to a PCI facility and routine performance of PCI 2 to 6 hours after thrombolysis—in conjunction with aggressive early dual oral antiplatelet therapy and “downstream” glycoprotein IIb/IIIa inhibition. This approach is associated with outcomes similar to those of primary PCI.^15–17,37

Prehospital thrombolysis delivered by paramedics and followed by early transfer to a PCI facility has been associated with further reduction in mortality rates compared with in-hospital thrombolysis (as in the Swedish registry⁴³), and a reduction in death rate comparable to that of primary PCI in patients presenting early. This is an adequate strategy in regions where such a system can be established.^{5,17,38,43,44}

Patients presenting more than 3 to 4 hours after symptom onset, older patients, and patients with lower-risk MI or a higher risk of bleeding may still be suited for primary PCI even when the door-to-balloon time is 90 to 120 minutes, as stated by the European guidelines,³² or when the PCI-related delay time is as long as 100 minutes. ¹⁰ On the other hand, while the ACC/AHA guidelines recognize that in these patients the mortality advantage of primary PCI vs thrombolytic therapy is maintained with more prolonged door-to-balloon times, they nevertheless state that the focus should be on developing systems of care to increase the number of patients with access to primary PCI in less than 90 minutes rather than extending the acceptable window for door-to-balloon time.

In conclusion, for patients presenting with ST-elevation MI who cannot undergo timely primary PCI, the best approach seems to be prehospital thrombolysis delivered by paramedics or local thrombolysis at the non-PCI hospital followed by transferring the patient and performing PCI within a few hours. This is especially important in patients with high-risk ST-elevation MI who present early after symptom onset, when the extent of myocardial necrosis associated with delayed primary PCI is largest.

In addition, every community should develop a coordinated transfer strategy between non-PCI and PCI hospitals.