Toronto, ON - Rescue PCI does appear to be the best strategy for STEMI patients who have failed thrombolysis, a new meta-analysis suggests [1].

The meta-analysis, which is published in the January 30, 2007, issue of the Journal of the American College of Cardiology, found that patients receiving rescue PCI showed improved clinical outcomes compared with those given conservative treatment but that repeat thrombolysis was not associated with significant clinical improvement and may be associated with increased harm.

Lead author Dr Harindra Wijeysundera (University of Toronto, ON) commented to heartwire: "This meta-analysis is the largest dataset comparing treatment strategies for patients who have failed thrombolysis. Our results suggest that rescue PCI is associated with a reduced risk of repeat MI and heart failure, but this does come at a cost of some increased minor bleeding. My advice would therefore be that rescue PCI is the preferred strategy, but that it needs to be performed by an experienced operator if possible, and steps need to be taken to minimize bleeding risks."

In the paper, the authors note that thrombolysis restores normal flow in only about half of STEMI patients, as assessed angiographically at 90 minutes, with even less success in elderly patients and in those with cardiogenic shock. Given that one half of the 500 000 STEMI patients treated annually in the US receive thrombolytic therapy, almost 125 000 patients a year will have suboptimal reperfusion and poorer outcomes. Wijeysundera explained that the area of rescue treatment after failed thrombolysis is very difficult to study, as reflected by the few trials on this subject in the literature, and the ones that have been done seem to have had problems recruiting the required number of patients. "It is difficult to enroll patients who fail thrombolysis, as doctors appear reluctant to randomize in a trial where one option is not doing anything, even though it is not known for sure that actively treating is any better. There is an instinctive feeling that doing nothing is not right, and it is better to try repeat thrombolysis or PCI. As angioplasty facilities have become more common, there is now a tendency to send these patients for PCI, even though the data are not that solid on whether this is the best option. As it is difficult to perform large studies, this area lends itself well to meta-analysis," he added.

One of the most recent randomized studies in this field is the REACT study, which compared conservative treatment, repeat thrombolysis, or PCI. This suggested that rescue PCI was preferable on a composite end point. "We wanted to do this meta-analysis to see whether we could find an effect on the hard individual end points of mortality, MI, and CHF, and if the bleeding side effects associated with rescue PCI or repeat thrombolysis were acceptable, as there is known to be an increased risk of bleeding with both procedures," he said.

Wijeysundera et al included eight trials enrolling a total of 1177 patients with follow-up duration ranging from hospital discharge to six months. Results showed that rescue PCI 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. There was no increase in major bleeding, but there was a significant increase in minor bleeding (mainly access site bleeds) and strokes.

The authors note that the overall absolute reduction in the composite end point of all-cause mortality, heart failure, or reinfarction was substantial in the rescue-PCI group, requiring only nine patients to be treated for benefit.

In contrast, repeat thrombolysis was not associated with significant improvements in all-cause mortality or reinfarction, and it also showed an increased risk for minor bleeding

"The dataset on repeat fibrinolysis was smaller, but we did not show any benefit on mortality or re-MI and [there was] an increased bleeding risk, so we do not recommend that another dose of thrombolysis be given if reperfusion has not been achieved with a first one," Wijeysundera commented to heartwire. "This also makes sense from a pathophysiological view, as the infarct thrombus becomes more resistant to lysis as time passes, so it seems unlikely that a second dose would work if the first one did not."

He added: "Our results suggest that PCI is the right strategy for patients who have failed thrombolysis. While we didn't see a significant reduction in mortality, there was a favorable trend and the reductions in re-MI and CHF are meaningful." He pointed out that the total number of strokes in the analysis was small (10 with rescue PCI vs two with conservative therapy) and, surprisingly, the majority of these strokes were ischemic, not hemorrhagic. "This is not what we would expect. As rescue PCI is associated with an increased risk of bleeding, you would expect a higher incidence of hemorrhagic stroke in the PCI group, but there seemed to be a higher incidence of ischemic strokes instead, and this, together with the small numbers, make any strong statements on the stroke results difficult.

"Given the difficulty in enrolling these patents, I don't anticipate that there will be any more trials in this particular indication. And from these results I would recommend patients with no evidence of reperfusion at 90 minutes after thrombolysis should be sent for PCI. In the trials we included, the rescue PCI was performed up to five hours after thrombolysis. This is a fairly generous time frame, which should allow most patents to get to PCI, even if it involves transfer to a different hospital," he concluded.

In the paper, the authors add that to further improve outcomes and minimize risks, randomized trials should be performed to determine the most appropriate adjunctive pharmacotherapy in patients undergoing rescue PCI.