Vienna, Austria - The long-awaited results from the FINESSE trial should put to rest once and for all the idea that using a half-dose lytic plus abciximab, or abciximab alone, can improve on primary PCI in acute ST-elevation MI, at least in patients who can undergo PCI within one to four hours of first medical contact. Dr Stephen Ellis (Cleveland Clinic, OH), who presented the results here at the European Society of Cardiology Congress 2007, offered the caveat that there still may be other drugs that might be worth considering in the future or possibly patient groups who might benefit who were not included or identified in the trial.

Dr Stephen Ellis

But overall, Ellis said, "I think it's fair to say that for the fairly large number of patients who might have been candidates for facilitated angioplasty, that of the major approaches that have been tested—thrombolysis in ASSENT V or a combination thrombolytic plus a GP IIb/IIIa antagonist or antagonist alone as tested in our study—none of these have worked out. They cause harm or they've failed to show benefit and have increased bleeding. So with those drugs in particular, I think the facilitated strategy should be put aside. . . . In terms of using this as part of a broad approach for patients, I think it's dead."

The results will disappoint physicians who have argued that the strategy, intuitively, makes sense: open the artery as soon as possible, then proceed with guideline-recommended intervention.

"Many things in cardiology may sound nice, but you have to test whether they work for our poor patients," Dr Freek Verheugt (Nijmegen University, the Netherlands) commented to heartwire. In FINESSE, he said, "There's a slight tendency toward efficacy, but there is also more bleeding, and the beneficial effects are in fact so minimal that it is clear this is not a way to go. So this saves us money, and this saves bleeding complications. This is the biggest trial of facilitated angioplasty so far, using the most modern therapies. . . I think it's clear that you shouldn't use this as a routine strategy."

Sometimes you need a little FINESSE

Dr Freek Verheugt

FINESSE enrolled 2452 patients with an estimated time to cath lab of one to four hours, randomized in a 1:1:1 fashion to primary PCI with in-lab abciximab, upfront abciximab-facilitated primary PCI, or half-dose reteplase/abciximab-facilitated PCI. Investigators were interested in whether the combination strategy would be better than abciximab alone or whether abciximab facilitation would be better than primary PCI with abciximab given in the cath lab. Enrollment in the study was halted in December 2006 at 82% of its planned size, despite having failed to reach its target enrollment of 3000 patients, due to slow enrollment and financial overruns.

At 90 days, Ellis and colleagues saw no differences between treatment arms for the primary composite end point of the trial: all-cause mortality, readmission for heart failure, ventricular fibrillation, or cardiogenic shock. There were also no differences in all-cause mortality, complications of MI, or any of the independent components of the primary composite end point. For safety end points, rates of TIMI nonintracranial major bleeding and minor bleeding were significantly higher for the abciximab/lytic facilitated PCI strategy as compared with primary PCI. Major and minor bleeding combined was statistically more common in the combination strategy as compared with primary PCI and as compared with the abciximab-only group.

There was also a "strong trend" toward increased intracranial hemorrhage through discharge or day seven in the combined abciximab/lytic facilitation approach.

Primary, secondary, and bleeding end points in FINESSE

End point	Primary PCI (%)	Abciximab-facilitated (%)	Combination (abciximab/reteplase)-facilitated (%)	p, combination-facilitated vs primary PCI	p, combination-facilitated vs abciximab-facilitated
Primary end point*	10.7	10.5	9.8	NS	NS
All-cause mortality	4.5	5.5	5.2	NS	NS
Complications of MI	8.9	7.5	7.4	NS	NS
CHF requiring hospital/ED visit	2.2	2.9	1.9	NS	NS
Death	4.5	5.5	5.2	NS	NS
Cardiogenic shock	6.8	4.8	5.3	NS	NS
VF	0.4	0.2	0.6	NS	NS
TIMI major bleeding	2.6	4.1	4.8	0.025	NS
TIMI minor bleeding	4.3	6.0	9.7	<0.001	0.006
TIMI major or minor bleeding	6.9	10.1	14.5	<0.001	0.008

Widening the window

According to Ellis, the overall outcomes in FINESSE were better than expected in patients with longer delays, resulting in lower power than originally anticipated. This finding also opens up the possibility that the accepted 90-minute window used as a cutoff to decide whether patients should be treated with lysis or primary PCI could be safely widened.

"I think primary angioplasty is the default strategy, and there are only two areas where there are still some questions," he told heartwire. "The first area is patients who present early within the first hour or so of symptom onset in whom lytics may be just as good or better than primary PCI. And the other question has to do with prolonged door-to-balloon times, and for that there remains some uncertainty. The guidelines would say if there's more than a 90-minute difference you should go with lytics. But the FINESSE trial would suggest that you can probably extend the duration of that window, although the duration of that window is not well-defined."

One of the complicating factors, he notes, is estimating time from symptom onset to hospital. "In the field, it's often very hard to judge how long it's going to take to get to the cath lab. You may think it's going to be two hours, but many times, because of weather or transportation delays, it ends up being five hours. And that's part of the physician's dilemma. And that may be why facilitation isn't quite dead, because maybe there's a role beyond four hours and it hasn't even been studied."

Particularly in countries like the US, where 40% of patients now receive primary PCI but other patients face long treatment delays, physicians are making decisions with little to back them up, Ellis observed.

"There really is a lot of confusion in the US about what to do, and they're giving all sorts of regimens that aren't approved, trying to the right thing. But heretofore they didn't have much data on which to base their decisions. Now they have some data."

But those data do not offer guidance on what to do with a patient who presents just after the four-hour cut point used in FINESSE. "If it's closer to six hours, that's a real dilemma, because we don't really have the trial to answer that question. You're probably on more solid grounds to give full-dose lytics, because that's what's approved. But one could make the argument that, particularly for patients who are at low risk for bleeding, half-dose lytics and a GP IIb/IIIa antagonist is at least as logical if not more logical, it's just not approved."

And Ellis is doubtful that a trial will ever be done to answer the question. "This is all physicians are going to get. They're going to have to live with this information and treat their patients on the basis of this."

Disappointments and possibilities

Other commentators also expressed disappointment over the results. Dr Anthony Dalby (University of Witwatersrand, Johannesburg, South Africa) emphasized that FINESSE, along with the CARESS trial also presented today, together make a "strong case" for primary PCI. But he doesn't rule out the use of a facilitated approach for certain patients.

"I think there may be some high-risk cases in which you'd want to have some of this lytic or antiplatelet therapy on board—it might be proactive in patients with high thrombus burden, for example—but you've got to be selective. But the first and strongest message is that intervention makes a big difference. We knew that, but this is a reminder."

Dr Frans Van de Werf (University of Leuven, Belgium), the discussant for the study, also held out the possibility for a facilitated strategy, which he suggested should be renamed a "pharmacoinvasive strategy."

He agreed that all of the trials to date "do not support a strategy of facilitated PCI. . . . Facilitation with a high-dose lytic, GP IIb/IIIa inhibition, or a combination therapy cannot be recommended at present."

But he also outlined the specific circumstances in which a pharmacoinvasive strategy might work: "If the open-artery hypothesis is still valid—and I believe it is—a strategy of an early lytic-based pharmacologic treatment preceding PCI can only be beneficial in patients presenting early, within two to three hours, with a large amount of viable myocardium, an anticipated long delay to PCI, who also receive adequate antithrombotic cotherapy, and in whom PCI is postponed if there is evidence of successful TIMI 3 reperfusion after pharmacological treatment."

Some answers, he added, may yet come from the STREAM trial, still in its early stages.

Ellis disclosed receiving research grants from Centocor and Eli Lilly. Van de Werf disclosed ties to numerous major pharmaceutical companies.