Rescue Angioplasty: The REACT Trial
Abstract & Commentary
By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.
Synopsis: Event-free survival after failed thrombolytic therapy was significantly higher with rescue PCI than with repeated thrombolysis or conservative treatment.
Gershlick AH, et al. Rescue Angioplasty After Failed Thrombolytic Therapy for Acute Myocardial Infarction. N Engl J Med. 2005;353:2758-2768.
Thrombolysis therapy of acute myocardial infarction (MI) results in TIMI 3 flow in about 60% of patients. What to do with the remaining patients is controversial. Thus, the results of the Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis (REACT) trial are of interest. The multi-center, randomized, parallel group trial was conducted in the United Kingdom between 1999 and 2004. Patients with acute ST-segment elevation MI treated with thrombolytics within 6 hours of pain onset, in whom ST-segment elevation failed to decrease > 50% in 90 minutes, were eligible for inclusion. Crossovers were allowed if the clinical results were unfavorable. Over half of the 35 centers participating had no cardiac catheterization facilities, so patients were transported to a center that did, if randomized to rescue angioplasty. The primary end point was the combination of major adverse cardiac and cerebral events at 6 months (death, recurrent MI, stroke, heart failure). Secondary end points included revascularization and bleeding. The 427 patients were randomized to the 3 groups (about 140 in each group). Event-free survival was 85% for rescue angioplasty, 70% for conservative therapy, and 69% for repeat thrombolysis (P = .004). There was no difference in mortality for all causes. Freedom from revascularization was more frequent with rescue angioplasty; 86% vs 78% conservative therapy and 74% repeat thrombolysis (P = .05). Nonfatal bleeding was more common with rescue angioplasty, mainly from the sheath site. The results were the same whether intention to treat or actual therapy were used. The median transfer time for rescue angioplasty, if necessary, was 85 minutes (range, 55-120). Rescue angioplasty was accomplished in a median of 414 minutes after pain onset (range, 350-505). Stents were used in 67%, and 43% received platelet glycoprotein IIb/IIIa receptor inhibitors.
There was a trend for lower mortality at 6 months with rescue angioplasty (5% vs 13% for both other groups combined P < .05). Stroke and heart failure were not different between groups. Recurrent MI was less with rescue angioplasty (2% vs 11% and 9%, P = .004).
Gershlick and colleagues concluded that rescue angioplasty, even if intra-hospital transfer is required, is superior to repeat thrombolytic therapy or conservative therapy for preventing major adverse cardiac and cerebral events.
Rescue angioplasty has been controversial, and the recently published MERLIN trial (J Am Coll Cardiol. 2004;44:287) showed only a decrease in subsequent revascularization with rescue angioplasty. This study showed a reduction in the composite end point of major cardiac and cerebral events, recurrent MI and revascularization compared to conservative therapy and repeat thrombolysis. There was a trend toward lower mortality in the rescue group. These beneficial effects occurred despite the necessity to transfer about 40% of the patients to another facility for angioplasty, which cost a median of 84 minutes.
Why this study showed more benefit than the MERLIN study is probably related to study details that change with time. The MERLIN study is at least 2 years older, and streptokinase was the thrombolytic used in 96% vs 59% in this study. Also, less stents and IIb/IIIa agents were used in MERLIN. In addition, there was considerable cross-over from the conservative arm to the repeat thrombolysis arm, which did not happen in this study, which only had 4% of patients who did not receive their assigned treatment. Finally, only 8% of rescue angioplasty attempts failed in this study. This is important because observational data suggest that patients with failed rescue angioplasty have a worse prognosis.
Nonfatal bleeding, mainly from the sheath site, was more common in the rescue group, but fatal bleeding was more common in the other 2 groups (P = .005). Also, when the rescue group was compared to both other groups combined, the lower mortality in the rescue group was significant. This trial was stopped early because of falling enrollment and a finite funding period by the steering committee. The 80% power calculation suggested that about 156 patients per group would be required, but when the study ended there were 141-144 patients in each group. Had the trial continued, more robust results may have occurred, but certainly the direction of the results would not have changed. These results suggest that rescue angioplasty is now the treatment of choice for failed thrombolysis in acute ST elevation MI.