Linkoping, Sweden - A new registry study involving more than 26 000 STEMI patients from Sweden has shown reductions in short- and long-term mortality, reinfarction rate, and hospital stay with primary PCI vs thrombolysis, adding to the evidence from randomized trials showing that PCI is superior to thrombolysis [1]. This registry study provides the first large-scale comparison of primary PCI with prehospital thrombolysis and suggests that primary PCI provides better outcomes.

The study is published in the October 11, 2006 issue of the Journal of the American Medical Association. The authors, led by Dr Ulf Stenestrand (University Hospital, Linkoping, Sweden), conclude that "if available, primary PCI today is the treatment of choice for STEMI" and that prehospital thrombolysis might offer a comparable alternative "only if delivered within two hours of onset of symptoms in areas with more than four hours' transportation time to a PCI procedure."

In an interview with heartwire, Stenestrand said these data, along with a recent meta-analysis by Boersma et al of randomized trials comparing primary PCI with thrombolysis [2], suggest that the extra time taken to perform PCI rather than give thrombolysis (known as the PCI delay) can be much longer than previously thought and still show a benefit of PCI. "We used to think the PCI delay had to be under about 90 minutes for PCI to be preferable, although there was not much hard information to support this. But our results and those of Boersma et al suggest it is more like four to five hours, and our study was three times larger than the largest meta-analysis of previous studies," he commented.

Stenestrand pointed out that in his study, mortality in patients treated within the first hour of symptom onset was 9.5% in those given thrombolysis vs 6.5% in those receiving PCI. "It took a delay of five hours for the mortality rate in the PCI patients to reach 9.5%," he noted, adding, "We haven't been able to pinpoint the PCI delay time before but, because we had so many patients in this study, we [were able to] get a better estimate of this."

"In the Boersma meta-analysis, similar results were seen—not until after six hours of presentation delay does primary PCI have higher 30-day mortality [than] thrombolysis within the first hours. So with our registry study and this previous meta-analysis of randomized trials, I believe the case is clear and closed. Primary PCI is better even if transportation would [take] up to four hours," Stenestrand told heartwire. "I would say that in normally populated areas, where you can get to a PCI center in a couple of hours, there is no place for thrombolysis any more."

In their introduction, Stenestrand et al point out that several recent meta-analyses have suggested better survival with primary PCI than with thrombolysis, but whether similar results could be achieved in real-life settings and whether prehospital thrombolysis given within the first hours after the onset of symptoms provides similar or better results have not been established.

They therefore compared the outcomes of primary PCI with prehospital and in-hospital thrombolysis in STEMI patients admitted between 1999 and 2004 in the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). This registry comprised all patients admitted to 75 hospitals with coronary-care units in Sweden. The study looked at data from 26 205 consecutive STEMI patients who received reperfusion therapy within 15 hours of symptom onset. Of these, 7084 underwent primary PCI, 3078 received prehospital thrombolysis, and 16 043 were given in-hospital thrombolysis.

Results showed that after adjustment for age and comorbidity, prehospital thrombolysis was associated with better outcomes than in-hospital thrombolysis but that primary PCI was associated with lower mortality, a lower reinfarction rate, and shorter hospital stays than either prehospital or in-hospital thrombolysis.

It was also noted that a treatment delay of two hours or more after the onset of chest pain was associated with a sharp increase in mortality rates in the thrombolysis groups, but far less so in the primary-PCI group.

The researchers note that this registry study provides data on a large unselected population of consecutive patients with STEMI of all ages who were managed with all kinds of reperfusion strategies from all hospitals in a single country with complete long-term follow-up concerning mortality and morbidity.

Although they concede that an observational cohort study cannot provide the same degree of evidence of superiority for specific treatments as a randomized trial or a meta-analysis of randomized trials, they point out that this study had twice as many patients in the primary-PCI group and four times as many in the in-hospital thrombolysis group as in the most recent meta-analysis of randomized trials comparing these two treatments.

Furthermore, this is the first time primary PCI has been properly compared with prehospital thrombolysis "because the database contained seven times as many of these patients as in the only reported randomized trial, and 17 times more than the French registry study [3]," they comment.

"In accordance with many previous reports, our study showed that the benefits of all types of reperfusion treatment depend on the treatment delay, but that the loss in benefit by longer delay is less pronounced and appears later with primary PCI than with thrombolysis. Therefore, the relative mortality benefits with primary PCI might amount to approximately 20% during the first hours but increase to 35% after four to seven hours," they write.

They also point out that in contrast to the two French studies—CAPTIM [4] and the USIC 2000 Registry [3]—in this Swedish study, in patients with very short treatment delay, primary PCI appeared to be associated with lower mortality rates than thrombolysis. They suggest that this might be because the French studies had low statistical power and were performed between 1997 and 2000, when the results with primary PCI were less successful.

Stenestrand et al conclude: "This large registry study with complete long-term follow-up of all unselected consecutive patients from almost all coronary-care units in an entire country clearly indicates a superiority of primary PCI for the treatment of STEMI in the real-life setting."