Introduction
Thrombolytic therapy for Acute ST Elevation Myocardial Infarction remains most practical and easy method of reperfusion, although Primary PTCA is shown to be superior in many ways. Successful reperfusion is identified by – resolution of chest pain, reperfusion arrhythmias most commonly Accelerated Idio Ventricular Rhythm (AIVR), and ST segment Resolution (STR) >50% in the lead with maximum ST elevation in pre-Thrombolytic ECG. Early and complete reperfusion is a major determinant of 30-day mortality in STEMI patients treated with Thrombolytic therapy 1. The major limitation of Thrombolytic therapy is failure to restore infarct related artery patency in approximately 20-30% of patients 2 so called Failed Thrombolytic therapy. Several methods are available to treat patients with failed Thrombolysis such as re-administration of Thrombolytic agents, administration of GpIIb-IIIa agents, IABP and Rescue Angioplasty. Rescue angioplasty is defined as PCI within 12 hours after failed fibrinolysis for patients with continuing or recurrent myocardial ischemia. It is not established clearly which therapeutic strategy is best for patients who failed Thrombolytic therapy.
Rescue angioplasty should not be confused with more recent concepts such as Facilitated Angioplasty meaning angioplasty after pharmacotherapy such as GpIIb-IIIa inhibitors and or Thrombolytic agents administered just before or hospital arrival, and Systematic Angioplasty meaning routine angioplasty after Thrombolytic therapy regardless of successful reperfusion and FAST-PCI meaning administration of half dose Thrombolytic pre-hospital or in peripheral hospital and referral to PCI center. Recent ACC/AHA and European guidelines recommend rescue angioplasty as a potential therapy for patients who fail Thrombolytic therapy 3, 4.
Rescue Angioplasty
The clinical outcomes of patients who failed reperfusion in the large fibrinolytic trials (GUSTO, TAMI, TIMI) and who were treated by rescue PCI were reported in the late 1980s. The major observations were high re-occlusion rates and 39% mortality if
Rescue Angioplasty failed. The role of Rescue Angioplasty for failed thrombolysis was debated in early 1990s. |
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Ellis et al., on behalf of RESCUE Investigators showed Rescue Angioplasty was useful in the prevention of death or severe heart failure, with improvement in exercise, but not resting, ejection fraction 5. Further, a meta-analysis performed by Ellis and coworkers showed that patients with TIMI 0–1 flow had better outcomes after Rescue Angioplasty than with conservative treatment 6. Thus the concept of Rescue Angioplasty began to be accepted in Interventional Cardiology. While these earlier studies were done using balloon angioplasty, Schomig et al have shown that coronary stenting was associated with greater myocardial salvage compared to plain balloon angioplasty 7. Stenting in this situation is associated with larger lumen diameter, better TIMI grade III flows, lower re-occlusion rates and ensures better coverage of the plaque and dissections.
Rescue Angioplasty gained definite place for failed thrombolysis on the basis of two large randomized studies from United Kingdom namely – MERLIN 8 and REACT 9 trials. Both studies included patients who failed thrombolytic therapy based on STR >50% in the lead with maximum ST Elevation, but the difference in the inclusion criteria was ECG at 60 min in MERLIN study while it was 90 min in REACT study. The Middlesbrough Early Revascularization to Limit InfarctioN (MERLIN) trial randomized a total of 307 patients with STEMI and failed fibrinolysis to emergency coronary angiography with or without rescue PCI (n =153) or conservative treatment (n=154). Rescue Angioplasty group was associated with fewer incidences of re-infarction (7.2% vs. 10.4%, p = 0.3) and clinical heart failure (24.2% vs. 29.2%, p = 0.3) compared to conservative arm, at the cost of higher Strokes (4.6% vs. 0.6%, p = 0.03) and blood transfusions (11.1% vs. 1.3%, p = 0.001). The composite secondary end point of death/re-infarction/stroke/subsequent revascularization/ heart failure (37.3% vs. 50%, p = 0.02) was significantly better in Rescue Angioplasty group, although there was no difference in mortality (9.8% vs. 11%, p = 0.7) or Left ventricular function at 30- days. Of note, there was improved event-free survival in the rescue PCI arm, largely owing to a decrease in subsequent revascularization procedures (6.5% vs. 20.1%, p, 0.01). The REACT trial randomized 427 patients with failed thrombolysis to repeat thrombolysis (142 patients), conservative treatment (141 patients), or rescue angioplasty (144 patients). The primary |
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end point was a composite of death, re-infarction, stroke, or severe heart failure within six months. In the rescue-PCI group, 15.3 percent of the patients reached at least one component of the primary end point, as compared with 31.0 percent in the repeated-thrombolysis group and 29.8 percent in the conservative-therapy group (overall p = 0.003). Rescue angioplasty group was associated with significantly lower incidence of recurrent myocardial infarction (2.1% vs. 10.6% and 8.5%), repeat revascularization (13.2% vs. 23.2% and 20.6%) and demonstrated a trend towards lower mortality (6.2% vs. 12.7% and 12.8%) compared to repeat thrombolysis and conservative therapy group.
The short term benefits of Rescue Angioplasty, most importantly reduction in re-infarction and repeat revascularization are conclusively demonstrated in the above two trials. Prevention of re infarction is one of the most important aspects as it is associated with very high in hospital mortality ranging between 24%-41%. On long term follow up, patients who underwent Rescue Angioplasty in the MERLIN trial had less repeat revascularization (12.4% vs. 29.9%), and no mortality benefit (14.4% vs. 13.0%) compared to conservative arm 10. It may be argued that with contemporary methods of treatment these results would be much better. Some of the reasons to support this argument are: in the MERLIN trial there was very high usage of Streptokinase (96%), which is non- fibrin specific agent, low usage of coronary stents (50.3%), low usage of Glycoprotein IIb-IIIa agents (3.3%), non-performance of PCI to IRA in 42 patients as TIMI III flow was seen on angiography in cath lab (18% of them had unplanned revascularization during follow up).
A recent Meta analysis of 8 trials and 1177 patients concluded that Rescue angioplasty was associated with no significant reduction in all-cause mortality, but was associated with significant risk reductions in heart failure and reinfarction when compared with conservative treatment 11. The authors have concluded that repeat fibrinolytic therapy was not associated with significant clinical improvement and may be associated with increased harm.
Unanswered questions
Firstly, it is important to identify failed thrombolysis. Even though it is accepted that failed thrombolysis is identified by lack of chest pain relief, lack of ST resolution and lack of reperfusion arrhythmias, it should be remembered that these parameters do not have high predictive value. Secondly, at which point of time the ECG reading should be done to assess STR – whether 60 or 90 minutes is another important issue, as in the trials some patients were found to have recanalized artery by the time they were taken to Catheterization. Thirdly, some patients may have clinically successful reperfusion, yet on subsequent angiography, may have totally occluded vessel. Fourthly, failed rescue angioplasty is associated with high incidence of adverse outcomes (approximately 30 percent). 12 What strategy should be adapted in these situations is unclear.
Studies published recently have addressed the role of routine PCI after full dose thrombolytics (GRACIA-1, SIAM III, and CAPITAL-AMI) 13-15, after half dose thrombolytic with Gp IIb-IIIa inhibitor (CARESS-in-AMI, AMICO) 16-17 and are likely to change the practice in favor of pharmaco-invasive approach.
Conclusions
From the available evidence, it may be concluded that Rescue Angioplasty should be considered in patients who failed thrombolysis. Rescue Angioplasty is associated with short-term benefits in terms of reduction of re – infarction and reduction of heart failure and repeat revascularization and long term benefit of reduction in repeat revascularization.
References
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3. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). J Am Coll Cardiol 2004; 44:e1–211. |
4. Van de Werf F, Ardissino D, Betriu A, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 2003;24:28–66.
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8. Sutton AG, Campbell PG, Graham R, et al. A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-segment elevation myocardial infarction: the Middlesbrough Early Revascularization to Limit INfarction (MERLIN) trial. J Am Coll Cardiol 2004; 44:287–96.
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12. Sutton AG, Campbell PG, Grech ED, et al. Failure of thrombolysis: experience with a policy of early angiography and rescue angioplasty for electrocardiographic evidence of failed thrombolysis. Heart 2000; 84:197-204.
13. Fernandez-Aviles F, Alonso JJ, Castro-Beiras A, et al. Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomized controlled trial. Lancet 2004; 364: 1045–53
14. Le May MR, Wells GA, Labinaz M, et al. Combined angioplasty and pharmacological intervention versus thrombolysis alone in acute myocardial infarction (CAPITAL AMI study). J Am Coll Cardiol 2005; 46: 417–24.
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17. Denktas A E, Athar H, Henry T D et al., Reduced-Dose Fibrinolytic Acceleration of ST-Segment Elevation Myocardial Infarction Treatment Coupled With Urgent Percutaneous Coronary Intervention Compared to Primary Percutaneous Coronary Intervention Alone. J Am Coll Cardiol Intv 2008; 1: 504–10
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