London, UK - The CARESS-in-AMI study, showing that immediate transfer for PCI improves outcome in high-risk STEMI patients treated at a noninterventional center with half-dose reteplase and abciximab, has been published in the February 16, 2008 issue of the Lancet [1].

The findings were first presented and reported by heartwire at the European Society of Cardiology meeting last year.

In the paper, the authors, led by Dr Carlo Di Mario (Royal Brompton Hospital and Imperial College, London UK), point out that although PCI is the preferred strategy for patients with STEMI, many patients cannot get PCI within the required time and are thus still treated with thrombolysis, and in most cases they are transferred for PCI only if there is no evidence of reperfusion or the patient develops hemodynamic instability.

They wanted to evaluate the strategy of routine PCI for all patients after lysis, and because previous trials have shown adverse outcomes with full-dose lytics followed by PCI, they opted for the use of half-dose lytic (reteplase) plus abciximab (to overcome the initial platelet activation induced by thrombolysis). Patients were all given this regimen and then randomly assigned to immediate transfer to the nearest interventional center for PCI or to management in the local hospital with transfer only in case of persistent ST-segment elevation or clinical deterioration. The trial was conducted in France, Italy, and Poland and recruited 600 patients aged 75 years or younger, as the half-dose reteplase/abciximab regimen was associated with an excess of intracranial hemorrhage in patients older than 75 years in GUSTO V.

Results showed that, of the 299 patients assigned to immediate PCI, 255 (85.6%) received PCI. Rescue PCI was done in 91 patients (30.3%) in the standard-care group. The primary outcome, a composite of death, reinfarction, or refractory ischemia at 30 days, was reduced in the immediate-PCI group. The rate of major bleeding showed a 47.8% proportional increase in the immediate group, but this was not significant because of the low absolute incidence of events.

Di Mario et al conclude: "The CARESS-in-AMI trial shows that after treatment with a combination of half-dose reteplase plus abciximab, urgent transfer for immediate PCI is a better strategy than standard therapy with clinically indicated rescue PCI. Our study provides evidence suggesting that all high-risk STEMI patients receiving thrombolysis should be routinely and immediately transferred for PCI. These data further support the need for established networks of PCI and non-PCI centers to allow rapid transfer of appropriate STEMI patients for urgent PCI."

They add, however, that the trial was extremely slow to recruit, reflecting its stringent inclusion and exclusion criteria, as well as the expansion of primary angioplasty in the participating countries. "We acknowledge, therefore, that the conclusions of this study are applicable only to a high-risk subgroup of STEMI patients with no access to primary angioplasty facilities," they write.

In an accompanying editorial, Drs Nicolas Danchin (Hôpital Européen Georges Pompidou, Paris, France) and Paul Armstrong (University of Alberta, Edmonton) point out that the overall result was largely driven by refractory ischemia, a difficult end point to assess in an open-label trial, and that the brief duration of unfractionated heparin in the rescue group (24 hours, or half the duration recommended by US guidelines), coupled with low use of aspirin and clopidogrel, probably contributed to the striking rise in refractory ischemia in the first few days after randomization. They add: "Excess major bleeding occurred in the immediate-PCI group, and concern about its long-term negative effects is wisely noted."

Danchin and Armstrong conclude: "Overall, CARESS-in-AMI suggests, but does not prove, that more liberal use of coronary angiography in a selected population has better results after combined half-dose reteplase and abciximab than does a policy of angioplasty restricted to rescue cases. Moreover, the optimum timing for PCI in this approach is unclear."

They add: "Before we accept the findings of CARESS-in-AMI, we must await results from ongoing studies, including TRANSFER, and incorporate additional advances in medical therapy that decrease the risk of reinfarction and recurrent ischemia after fibrinolysis. Then we will know whether mechanical intervention beyond rescue in the first 24 hours is required for some or all patients with STEMI. Pending these results, organization of networks to move patients given a thrombolytic drug to institutions with catheterization laboratories seems a reasonable option, since primary angioplasty cannot be implemented everywhere."