Dr Francisco Avils

"The philosophy of this approach is to open the time frame to early PCI patients, which means allowing more patients to receive an intervention in the early phase of PCI, independent of geographical and logistic barriers," explained principal investigator Dr Francisco Avilés (Instituto de Ciencias del Corazón, Valladolid, Spain), referring to the dilemmas the two current approaches to acute STEMI present: PCI, although it is highly effective in restoring cardiac function and improving survival post-MI, needs to be performed within the first two hours and is thus available only to a small number of STEMI patients (about 20% in Europe and the US). Thrombolysis, on the other hand, is simple and available worldwide but has a limited applicability due to high incidence of reopening failure and reocclusion and a considerable risk of bleeding. "Less than 50% of patients with STEMI achieve optimal artery reopening plus effective myocardial reperfusion because of limited use and efficacy of the current therapies," Avilés pointed out at the GRACIA-2 presentation. PACT, SPEED, and GRACIA-1 (which was presented at last year's European Society of Cardiology Congress in Berlin) have shown the combination approach to be "feasible, safe, and beneficial," as reported by heartwire.

Less than 50% of patients with STEMI achieve optimal artery reopening plus effective myocardial reperfusion because of limited use and efficacy of the current therapies.

Therefore, his team conducted the first study evaluating the efficacy and safety of the facilitated approach: immediate thrombolysis followed by PCI vs direct PCI alone. They randomized 205 STEMI in 15 centers in Spain and Portugal patients to either:

Optimal primary PCI within 180 minutes of symptom onset.

Facilitated intervention with immediate tenecteplase administration, followed by PCI within three to 12 hours of symptom onset.

The primary study end point was infarct size, myocardial reperfusion, and left ventricular angiographic evolution at six weeks and six months. Additional end points included clinical evolution, death, and nonfatal MI.

Results in the two groups were similar with respect to delay from onset of symptoms and first medical contact, infarct size, and left ventricular evolution. However, a significantly higher percentage of patients receiving the facilitated approach achieved complete ST-elevation recovery and "clearly more TIMI-3 flow," as Dr Frans Van de Werf (Gasthuisberg University Hospital, Leuven, Belgium), who discussed the data afterward, pointed out. Moreover, cardiac function was found to be similar with both approaches after six weeks.

Clinical outcomes and complications at six months showed no significant differences between the groups. "Interestingly, unlike previous studies carried out before the use of stents and modern antithrombotic and antiplatelet agents, the incidence of major bleeding complications in the GRACIA-2 trial was very low, with no difference between primary angioplasty and facilitated intervention," Avilés reported.

Thus, the results of this "pilot study" establish safety and efficacy of PCI within three to 12 hours of facilitation with tenecteplase.

"There is still a high proportion of patients for whom primary PCI is not available [because of] logistic or geographical barriers who could benefit if they first receive treatment with thrombolytics," Avilés commented to heartwire. He said that he would definitely recommend the combination and that his facility was already applying it in patients not directly referred to them but arriving from a hospital without catheterization facilities, where they had already received thrombolysis with tenecteplase.

GRACIA-2, Van de Werf commented, was an "attempt to get rid of the two most important disadvantages of primary PCInamely, the limited availability and the deficiency in achieving reperfusion." He said that further studies, such as ASSENT-4, likely to be available in 2005, were needed to confirm the results of this pilot study. "Until then, pharmacological therapy before PCI should still be considered as an experimental treatment," he concluded. Avilés said that if those studies confirm facilitated intervention with tenecteplase to be as beneficial or even more beneficial than primary PCI, "the proportion of patients with heart attack who can benefit from early coronary stent angioplasty will increase dramatically."