Early PCI Following Lysis Superior to Watchful Waiting: Results of CARESS

C. Michael Gibson, M.S., M.D. September 3rd 2007

Vienna, Austria: The CARESS Trial (Combined Abciximab Reteplase Stent Study in Acute Myocardial Infarction) adds further data to support early PCI following lytic administration when compared to a strategy of watchful waiting. Small trials such as CAPITAL AMI had previously suggested such a benefit, but FINESSE is the largest randomized trial in the modern era of stents, lytics and GPIIbIIIa inhibitors to demonstrate a benefit.

What Are The Differences Between FINESSE and CARESS?
FINESSE evaluated whether pre-lytics can improve primary PCI outcomes. CARESS evaluated whether PCI can improve lytic outcomes.
 * In this trial all patients receive a primary PCI and either receive or don't receive a lytic.
 * In this trial all patients receive a lytic and either receive or don't undergo early urgent PCI.

Design of CARESS
CARESS addresses a common clinical question: After a patient receives a lytic at a hospital that does not perform PCI, is it better to manage them medically (n=300), or transfer them to a PCI facility urgently (n=297). In this trial, all patients were initially treated with reteplase, heparin and abciximab.

Among the patients urgently transferred, the time from reteplase to angiography was 136 minutes. This "Randomization to Angiography" time is shorter and different than a standard "Door to Balloon time". Some patients failed lysis and required transfer for PCI, and the time to angiography in these rescue PCI patients was 212 minutes.

Urgent PCI After Lysis Improves Outcomes
The primary endpoint of the study was death, reinfarction or refractory ischemia at 30 days. The primary endpoint occurred less frequently among patients transferred urgently for PCI (4.1% vs. 11.1%, p = 0.001). It should be noted that the benefit in the primary endpoint was driven predominantly by what may be considered the softer endpoint of reducing refractory ischemia (0.7% vs. 5.0%, p = 0.002). There was a trend for urgent PCI to reduce reinfarction (0.3% vs. 1.7%, p = 0.104). There was no difference in mortality in this very underpowered evaluation of the question (3.1% vs. 4.4%, p = 0.403) or stroke (1.4% vs. 0.7%). As might be expected, any bleeding was more frequent in the urgent PCI group (12.2% vs. 7.4%, p = 0.032), but major bleeding was not significantly increased in the urgent PCI group (3.7% vs 2.0%, p = 0.208).

Conclusions
It is again important to re-emphasize the differences between FINESSE and CARESS. FINESSE indicates that lysis does not improve PCI outcomes, but in contradistinction CARESS indicates that PCI improves lytic outcomes.

Clinically, this trial indicates that STEMI patients who present to non-PCI facilities may benefit from transfer to a PCI facility to reduce the risk of death, MI or refractory ischemia. It is important to note that these patients received abciximab along with the reteplase, which may have reduced thrombotic complications in the cath lab. These benefits do come at the risk of an increase in bleeding. Caution should be exercised when lytics are combined with abciximab in the elderly (those over 75 years of age), a combination which is currently not supported by the ACC/AHA STEMI guidelines. Patients over the age of 75 were excluded from CARESS. Whether patients would have faired just as well with the administration of a lytic alone rather than in combination with abciximab was not answered by this trial. It should also be noted that clopidogrel was not given immediately along with the lytic agent. The immediate administration of clopidogrel with a lytic did result in improved outcomes in the CLARITY trial, and this early clopidogrel strategy was not tested in CARESS.