VIENNA — The once-promising concept of pharmacologically facilitated percutaneous coronary intervention for patients with ST-elevation MI now appears relegated to the scrap heap on the basis of the negative results of the large definitive Facilitated Intervention With Enhanced Reperfusion Speed to Stop Events (FINESSE) trial.
“In terms of using [facilitated PCI] as part of a broad approach for patients, I think it's dead,” FINESSE coprincipal investigator Dr. Stephen Ellis said at the annual congress of the European Society of Cardiology.
Primary PCI has been shown to be superior to thrombolytic therapy as a revascularization strategy for most patients with STEMI, but delays in getting to the cath lab are common, particularly when transfer to another hospital is required. The hypothesis underlying facilitated PCI was that when a delay of an hour or more was anticipated, improved clinical outcomes would be achieved by opening the infarct-related artery early with a thrombolytic agent and/or glycoprotein IIb/IIIa inhibitor while waiting for PCI. FINESSE, the largest-ever facilitated PCI trial, showed that's not the case, said Dr. Ellis of the Cleveland Clinic Foundation.
FINESSE involved 2,453 patients in 20 countries who presented with STEMI within 6 hours of chest pain onset and had an anticipated 1- to 4-hour delay to cardiac catheterization for primary PCI. They were randomized to one of two facilitated PCI strategies or to primary PCI with abciximab administered in the cath lab. The facilitated PCI approaches studied were half-dose reteplase plus abciximab, or abciximab alone. Average door-to-balloon time was 2.2 hours.
The primary end point was a 90-day composite of all-cause mortality, rehospitalization or treatment of heart failure in the emergency department, cardiogenic shock, or resuscitated ventricular fibrillation occurring more than 48 hours post randomization. The rate was 10.7% with primary PCI, 10.5% with abciximab-facilitated PCI, and 9.8% with combined facilitation, a nonsignificant difference.
Moreover, there was a downside to the facilitated PCI approaches. Major bleeding occurred in 4.8% of patients with combined facilitation, 4.1% with abciximab facilitation, and 2.6% with primary PCI. The combined rate of TIMI major or minor bleeding was 14.5% with dual reteplase/abciximab-facilitated PCI, 10.1% with abciximab-facilitated PCI, and 6.9% with primary PCI. There was also a strong albeit nonsignificant trend for more intracranial hemorrhages in the combined facilitation group.
Discussant Dr. Frans Van de Werf said one explanation for the negative results was the use of suboptimal antithrombotic cotherapy. FINESSE, he noted, didn't require enoxaparin or up-front clopidogrel because the trial was designed prior to publication of persuasive evidence of the importance of these therapies in STEMI patients.
He added that FINESSE may also have been doomed because it studied the wrong population, since it enrolled patients presenting up to 6 hours after symptom onset. “It's clear that in patients presenting after 3–4 hours there's little to gain by a slightly higher patency rate achieved by giving pharmacological therapy,” asserted Dr. Van der Werf, professor and chairman of the department of cardiology at University Hospital Gasthuisberg, Leuven, Belgium.
While he concurred with Dr. Ellis that facilitated PCI using the strategy tested in FINESSE can't be recommended, Dr. Van de Werf also announced that a variant approach will be put to the test in a large randomized trial called to begin early next year. (See sidebar below.)
FINESSE was funded by Centocor and Eli Lilly.
'In terms of using [facilitated PCI] as part of a broad approach for patients, I think it's dead.' DR. ELLIS
'Pharmacoinvasive' Strategy in STEMI
A reinvigorated role for thrombolytic therapy in ST-elevation MI as an alternative to primary percutaneous coronary intervention will be studied in a 2,000-patient randomized multicenter trial to begin early next year, Dr. Van de Werf said.
The STREAM (Strategic Reperfusion Early After Myocardial infarction) trial will test what he termed a “pharmacoinvasive strategy” involving prehospital administration of tenecteplase to STEMI patients presenting within 3 hours of symptom onset and having an anticipated lengthy delay to PCI.
Unlike the facilitated PCI strategy, which has fallen by the wayside in the wake of the negative FINESSE trial, the pharmacoinvasive strategy restricts immediate PCI to those patients who don't demonstrate at least 50% ST-segment resolution in response to lytic therapy. In those who do show evidence of successful reperfusion after prehospital lytic therapy, cardiac catheterization will be postponed for up to 24 hours, explained Dr. Van de Werf, principal investigator in STREAM.
The STREAM hypothesis is that prehospital lysis provides outcomes as good as or better than primary PCI in patients presenting early with STEMI. Participants will receive state-of-the-art antithrombotic therapy with up-front clopidogrel and enoxaparin rather than unfractionated heparin in accord with the results of the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombosis In MI 28 (CLARITY-TIMI 28) and Enoxaparin and Thrombosis Reperfusion for Acute Myocardial Infarction Treatment-Thrombosis In Myocardial Infarction 25 (EXTRACT-TIMI 25) trials, added Dr. Van de Werf.