ST elevation myocardial infarction rescue percutaneous coronary intervention

For patient information click here

Associate Editor-In-Chief: Vijayalakshmi Kunadian M.B.B.S., M.D., M.R.C.P

Rescue PCI
Stated simply, this is performance of a PCI in a closed artery following fibrinolytic therapy. Rescue PCI is defined as the intent to administer a fibrinolytic agent in the setting of STEMI, and the performance of PCI for failure of the fibrinolytic agents is unintended. If there are clinical signs and symptoms of failure of the fibrinolytic agent to achieve reperfusion, then rescue PCI is performed to open the totally occluded artery. The strategy differs from facilitated PCI, a strategy in which the intent is to administer a fibrinolytic agent, and routinely perform PCI in the majority of patients even in the presence of or irrespective of signs and symptoms of successful fibrinolytic reperfusion. Rescue PCI is the subject of this chapter.

Primary PCI
Primary PCI is defined as the performance of percutaneous coronary intervention (PCI) (either conventional balloon angioplasty or coronary stent placement) in the setting of ST elevation MI (STEMI) without antecedent treatment with a fibrinolytic agent. The chapter on Primary PCI can be found here.

Facilitated PCI
Facilitated PCI is defined as the intent to perform a PCI (either conventional balloon angioplasty or coronary stent placement) in the setting of STEMI following treatment with either a full dose or half dose of a fibrinolytic agent. This approach is also termed a pharmaco-invasive strategy. This strategy differs from rescue or adjunctive PCI in that the intent of facilitated PCI is to perform PCI, and the administration of a fibrinolytic agent is intended to improve the PCI results. The chapter on Facilitated PCI can be found here.

Adjunctive PCI
Stated simply, this is performance of a PCI in an open artery following fibrinolytic therapy. Adjunctive PCI is defined as the intent to administer fibrinolytic agent in the setting of STEMI, and the performance of PCI for partial success of the fibrinolytic agent is unintended. If there are clinical signs and symptoms of incomplete reperfusion, then adjunctive PCI is performed to further open a patent artery (one with TIMI grade 2 or 3 flow). The strategy differs from facilitated PCI in that the intent is to administer a fibrinolytic agent, and the performance of PCI is intended to improve the fibrinolytic results.

Background
Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with an acute myocardial infarction (MI) if it is available in a timely fashion and can be performed by highly skilled interventional cardiologists. However, worldwide, fibrinolytic therapy continues to be used as the first line therapy in 30-70% of the population for the management of this condition. Fibrinolytic therapy has, however, a number of limitations. For instance, TIMI grade 3 flow is restored in only 54% of patients. Of these, around 5-10% of patients experience reocclusion of the infarct related artery following initial successful reperfusion using fibrinolytic therapy.

Previous ST elevation myocardial infarction (STEMI) trials have suggested full reperfusion of the infarct artery (TIMI grade 3 flow) is associated with improved clinical outcomes. Therefore restoration of coronary artery blood flow and myocardial perfusion by percutaneous coronary intervention (PCI) when a fibrinolytic agent has failed to restore complete flow appears to be a reasonable strategy.

Clinical trials
Although reports have been available since the mid 1980s regarding the use of rescue angioplasty, these data may now be mostly of historical interest as there have been significant developments in angioplasty techniques and in adjunctive pharmacotherapy. Preliminary studies on rescue angioplasty were first performed as part of large fibrinolytic trials. In the TAMI-5 trial, the benefit of rescue angioplasty was assessed among those who had fibrinolysis using TPA, urokinase and combination of both fibrinolytics. Among those who underwent rescue angioplasty for failed fibrinolysis, there was a trend towards increased patency rates of the infarct arteries on predischarge angiography compared to those who had delayed procedures (95% vs. 90%, p=0.065), improvement in regional wall motion abnormality in the infarct artery territory (p=0.004) and more patients were free from adverse events (67% vs. 55%, p=0.004).

Rescue angioplasty however, is faced with logistical hurdle of requiring transfer of patients to a PCI center. The feasibility of transfer of patients was studied by Vermeer et al. Patients were randomized to treatment with alteplase, fibrinolysis and transfer for rescue PTCA and primary PTCA. There was no significant difference in mortality between the three groups and the transport of patients was not associated with significant problems.

These initial studies led to randomized trials to evaluate the potential benefit of rescue angioplasty compared with conservative management. An initial randomized study of rescue angioplasty was performed by Ellis et al (RESCUE I) to determine the benefit of rescue angioplasty versus a conservative strategy for patients aged 21-79 years with failed reperfusion using fibrinolytic agents. This study included 151 patients with anterior myocardial infarction from 20 centers. Patients were randomized to rescue balloon angioplasty (n=78) or conservative therapy consisting of aspirin, heparin and vasodilators (n=73) following coronary angiography if the infarct related artery was occluded. Balloon angioplasty was technically successful in 92% of patients. Although there was no difference in the resting ejection fraction between the two groups, there was a significant improvement in the exercise ejection fraction with rescue angioplasty (43±15% vs. 38±13% with the conservative therapy, p=0.04). There was also benefit observed in terms of reduction in combined heart failure or death using the rescue strategy compared to the conservative strategy (6% vs. 17%, p=0.05). However, rescue angioplasty was not associated with a difference in death (5% vs. 10%, p=0.18) or heart failure (1% vs. 7%, p=0.11). This study had a number of limitations including the relatively small study sample size which consisted of patients with only anterior infarcts undergoing intervention in the left anterior descending artery. Patients with previous myocardial infarction and left main stem diseases were excluded from the study. Stents and glycoprotein IIb/IIIa inhibitors were not used in this study. This study was followed later by two small randomized studies which demonstrated a potential benefit of the rescue strategy.

In addition to these small randomized trials, the TIMI study group evaluated the benefit of rescue angioplasty in the TIMI (Thrombolysis In Myocardial Infarction) trials (TIMI 10B-14) in a non-randomized analysis. In an analysis of 1938 patients from TIMI 10B-14 studies, the investigators demonstrated that rescue angioplasty was associated with a reduction in 30-day mortality compared to conservative strategy (6% vs. 17%, p=0.01). Combined death and repeat myocardial infarction was also reduced in the rescue group (8% vs. 19%, p=0.01). Although in contrast to the RESCUE I study, abciximab was used in 45% of patients in the rescue group, this analysis is limited by the fact that this was not randomized. All patients who had acute myocardial infarction and were treated with fibrinolytic therapy (TNK or tPA) underwent coronary angiography at 90 minutes. If the infarct artery demonstrated TIMI 0/1 flow, rescue angioplasty was performed and if there was TIMI 2/3 flow adjunctive angioplasty was performed. Delayed angioplasty was performed among patients who presented >150 minutes after symptom onset. There was no difference in the outcome between the adjunctive and delayed PCI groups.

These data were subsequently followed by another sub-analysis from the TIMI 10B trial which provided outcome information for up to two years among patients undergoing rescue angioplasty compared to those who undergo medical therapy. In this analysis, rescue angioplasty was associated with improved mortality which extended to two years (p=0.03). Stents were used in 21% of patients who underwent rescue PCI and 3.1% of patients received glycoprotein IIb/IIIa inhibitor. In addition, this study also demonstrated that regardless of whether patients underwent rescue or adjunctive PCI and achieved TIMI grade 3 flow, the presence of TIMI myocardial perfusion grade 2/3 was associated with improved mortality.

In 2004, a moderate sized randomized study of patients undergoing rescue PCI versus conservative therapy for failed reperfusion using fibrinolytic therapy was published. The MERLIN trial (Middlesbrough Early Revascularization to Limit Infarction) consisted of 307 patients who were randomized to rescue PCI (n=153) and conservative therapy (n=154). There was no mortality benefit at 30 days for rescue PCI compared to conservative treatment (9.8% vs. 11%, p=0.7). However, there were differences in the composite secondary endpoints which consisted of death, reinfarction, stroke, subsequent revascularization and heart failure with a favorable outcome observed in the rescue group compared to the conservative group (37.3% vs. 50%, p=0.02). This difference was mainly due to an increase in subsequent revascularization in the conservative group compared to the rescue group (20.1% vs. 6.5%, p=0.01). In contrast, in the rescue angioplasty group, 4.6% of patients had a stroke or transfusion compared to 0.6% in the conservative group, p=0.03. Similar results were observed at 1 year and 3 year follow-up. It should be noted that stenting (50.3%) and glycoprotein IIb/IIIa inhibitors (3.3%) were used infrequently in the MERLIN trial. Subsequent to the MERLIN trial, the REACT (Rescue Angioplasty vs. Conservative or repeat Thrombolysis) trial (another UK trial) results were published. The REACT trial randomized 427 patients into three different groups. In addition to the conservative (n=141) and the rescue arms (n=144), the REACT trial had a repeat lysis arm (n=142). This study demonstrated that the event free survival (freedom from death, reinfarction, stroke or severe heart failure) was significantly greater in the rescue PCI group (84.6%) compared to the conservative group (70.1%) and the repeat lysis group (68.7%), p=0.004. Non fatal bleeding events were more common in the rescue PCI arm. Freedom from repeat revascularization was lower in the conservative group (77.6%) and the repeat lysis group (74.4%) compared to the rescue group (86.2%), p=0.05.

A sub-analysis from the REACT trial studied patients who were ≥70 years of age. The 6-month event free survival was significantly better among those who underwent rescue PCI compared to repeat lysis and conservative treatments (77.2% vs. 49.5% vs. 51.7%, p=0.031). There was also a trend towards reduced mortality and improved survival among those who had rescue PCI compared to repeat lysis and conservative treatment (87.5% vs. 69.4% vs. 69%, p=0.123). There was no increase in the incidence of minor or major bleeding events among the elderly in all three groups. This study suggests that rescue PCI in the elderly in the absence of cardiogenic shock might be a beneficial strategy.

A number of differences between the MERLIN and the REACT trials might explain the differences in outcomes between the two trials. First, MERLIN included patients who had <50% ST segment resolution at 60 minutes as opposed to 90 minutes in the REACT trial. Second, 96.4% of patients in the MERLIN trial received streptokinase (SK) and 60% of patients received SK in the REACT trial. Third, operators in the MERLIN trial used stents (50.3% vs. 68.5%) and glycoprotein IIb/IIIa inhibitors (3.3% vs. 43.4%) less frequently compared to the REACT trial.

Given the differences in the outcomes with rescue angioplasty among the randomized trials, three meta-analyses on rescue PCI have been performed. While the studies had different inclusion and exclusion criteria, overall rescue PCI was associated with a reduction in mortality and heart failure at 30 days. Rescue PCI was also associated with reduced reinfarction. These benefits however, occur at a risk of an increased risk of stroke and bleeding events.

Rescue PCI in the setting of cardiogenic shock
Randomized studies excluded patients in cardiogenic shock, a group of patients that might derive particular benefit. To this end, a prospective analysis consisted of patients who underwent primary PCI (n=65) and rescue PCI (n=59) in the setting of cardiogenic shock. In this study, glycoprotein IIb/IIIa inhibitors were used in 42% of cases in the primary PCI group and 20% of cases in the rescue PCI group (p=0.01). TIMI flow grade 3 was achieved in 74% of cases in the primary PCI group and only in 56% of cases in the rescue PCI group (p=0.04). One year mortality was significantly increased in the rescue PCI group compared to the primary PCI group (71% vs. 49%, p=0.01). Among patients who were >70 years of age rescue PCI was associated with 100% mortality rate at one year compared to the primary PCI group (70%). This study demonstrates that rescue PCI in the setting of cardiogenic shock is not associated with favorable mortality outcomes.

Predictors of Failed Rescue PCI and 1-year Mortality
A recent study analyzed 440 patients undergoing coronary angiography for failed fibrinolysis. Of these, 318 patients underwent rescue PCI. Rescue PCI was successful in 77% of cases (no in-lab death or emergency coronary artery bypass surgery and TIMI 3 flow). A successful procedure was associated with lower 1-year mortality compared to a failed procedure (14% vs. 43%). Older patients, diabetics, anterior infarcts, inter-hospital transfers, not current smokers and those in cardiogenic shock were likely to have a failed procedure. One year mortality was associated with older age (>75 years), cardiogenic shock and <TIMI 3 flow at the completion of the procedure.

Comparison with early transfer for PCI following pharmacotherapy
In situations where it is not always possible to transport patients to a PPCI center, in addition to a strategy of rescue PCI, the concept of a pharmaco-invasive strategy has been tested. While rescue PCI is performed when there is failed reperfusion with fibrinolytic therapy, facilitated PCI involves pretreatment with a fibrinolytic, glycoprotein IIb/IIIa inhibitor or a combination of both fibrinolytic and glycoprotein IIb/IIIa inhibitor in order to improve the outcomes of subsequent planned percutaneous coronary intervention.

In a recent study, Di Mario and co-workers demonstrated that immediate transfer for PCI following the administration of half dose fibrinolytic and a full dose abciximab among patients with acute ST elevation myocardial infarction was associated with improved clinical outcomes when compared to a conservative watchful waiting strategy in the CARESS-in-AMI trial (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction). A total of 600 patients treated with half dose reteplase, full dose abciximab, aspirin and heparin were randomized to either immediate transfer for PCI or transfer only in case of failed reperfusion (rescue group) or clinical deterioration. A total of 255 patients in the immediate transfer group underwent PCI and 91 patients in the conservative group underwent PCI for failed reperfusion. The 30-day mortality was lower in the immediate transfer group compared to the conservative group (4.4% vs. 10.7, p=0.004). There was no increase in bleeding events in the early PCI group (3.4% vs. 2.3%, p=0.47). Thus, early PCI after fibrinolytic administration is a better strategy than a watchful waiting conservative strategy.

This study has been characterized as testing the hypothesis that facilitated PCI would improve PCI outcomes. However, it is important to note that the study is not truly a study of a facilitated PCI strategy. The CARESS-in-AMI study determines whether early PCI improves pharmacotherapy outcomes. This study determines whether immediate transfer for PCI following the administration of half dose lytic and abciximab improves outcomes in the setting where a primary PCI facility is not readily available compared with a conservative strategy where rescue PCI is performed only in the setting of evidence of failed reperfusion or clinical deterioration. In order to test a facilitated PCI strategy, all patients would undergo PCI, and they would be randomized to receive either pharmacotherapy or placebo before the PCI. This would determine whether patients benefit from pre PCI pharmacotherapy.

Recommendations
Based on the evidences from the rescue PCI trials, the 2007 focused update of the American College of Cardiology/American Heart Association 2004 guidelines on the management of patients with ST elevation myocardial infarction provides a Class I indication for performing rescue angioplasty among patients who have failed fibrinolysis and have cardiogenic shock (among patients <75 years of age) [level of evidence B], severe heart failure and or pulmonary edema (level of evidence B) and hemodynamically compromising ventricular arrhythmias (level of evidence C).

Guidelines and recommendations
In 2007, the ACC/AHA published a focused update to their 2004 guidelines for the management of patients with STEMI:

Conclusions
Rescue PCI is associated with improved mortality and heart failure compared to conservative treatment. In small studies, the benefit of this therapy in elderly patients with cardiogenic shock is not clear.