News:Facilitated PCI: No Benefit in FINESSE

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

Design
FINESSE evaluated three strategies in ST elevation (STEMI) patients undergoing PCI:
 * 1) Pre-PCI abciximab plus half-dose thrombolytic (reteplase)(n=828)
 * 2) Pre-PCI abciximab alone (n=818)
 * 3) Pre-PCI placebo with abciximab during the procedure (n=806).

The trial was double blind. The aspirin dosing was 81 mg to 325 mg orally or 250 mg to 500 mg IV, and thienopyridines were administered at the discretion of the investigator. Heparin dosing was reduced to 40 U/kg bolus with a maximum of 3000 U).

GPIIbIIIa Inhbition Used to Offset Platelet Aggregation with a Lytic
Abciximab was continued for 12 hours after the procedure. The use of abciximab in all patients in the trial (with and without a lytic) is in contrast to ASSENT 4 where the minority of patients (about 10%) received a GP IIbIIIa inhibitor. The poor outcomes (including a higher rate of reinfarction) observed in ASSENT 4 were attributed in part to insufficient antiplatelet therapy to counter the platelet activation accompanying lytic administration. It was speculated that the more aggressive GP IIbIIIa regimen in FINESSE would overcome this problem.

Fairly Long Door To Balloon Times Allow Better Testing of the Hypothesis
Door to balloon times were 120 minutes in the 60% of patients who were randomized at a hospital with on site PCI and 155 minutes in the 40% of patients who were transferred from a spoke hospital into a hub hospital for a PCI. These delays are greater than that observed in ASSENT 4 where the overall delay was only 104 minutes. Thus, given this longer delay, this trial was in a better position than ASSENT 4 to test the hypothesis that in patients in whom a delay is anticipated, pre-treatment with a lytic would improve outcomes. The 155 minute delay among transfer patients is not that different than the current 170 minute delay in the US if a transfer is involved thus allowing reasonable testing of the benefit involved in administering a lytic prior to transfer.

Double the Patency Observed with a Lytic on Board
Not surprsingly, more patients in the pre-PCI reteplase+abciximab arm had an open artery prior to PCI (61%) compared with either the pre-PCI abciximab arm (26%; p < 0.001) or the pre-PCI placebo plus abciximab during the procedure (25%; p < 0.001). Another marker of pre-PCI epicardial and myocardial reperfusion, complete ST segment resolution (>70% ST resolution by 60-90 minutes) was also more common in the pre-PCI reteplase + abciximab arm (44%) than either the pre-PCI abciximab arm (33%; p = 0.013) or the pre-PCI placebo plus abciximab during the case arm (31%; p = 0.003).

Improved Pre-PCI Patency with Reteplase Fails to Improve Clinical Outcomes
Despite more than doubling pre-PCI patency, pre-PCI reteplase + abciximab was not associated with an improvement in the primary endpoint of death, cardiogenic shock, heart failure, or resuscitated ventricular fibrillation by 90 days. The primary ednpoint was observed in 9.8% of the pre-PCI reteplase + abciximab patients, 10.5% of the pre-PCI abciximab patients, vs 10.7% of the pre-PCI placebo + abciximab administered during the procedure; p = NS).

No Difference in Individual Components of the Primary Endpoint
No difference was observed in mortality (5.2%, 5.5%, 4.5%, respectively), heart failure (1.9%, 2.9%, 2.2%), cardiogenic shock (5.3%, 4.8%, 6.8%), or ventricular fibrillation (0.6%, 0.2%, 0.4%).

Pre-PCI Lytic was Associated with Increased Bleeding
Not surprisingly, the combination of TIMI major or minor bleeding was higher in the pre-PCI reteplase + abciximab arm (14.5%) vs the pre-PCI abciximab arm (10.1%; p = 0.008) or the pre-PCI placebo plus abciximab during the case arm (6.9%; p < 0.001). Intracranial hemorrhage occurred in 0.6% of the combination facilitated PCI arm but none of the abciximab facilitated PCI arm and in 0.1% of the primary PCI alone group (p=NS).

Conclusions
While pre-PCI reteplase did more than double pre-PCI patency, this was not associated with an improvement in the primary endpoint or clinical endpoints of LV function, but its administration was associated with an increased risk of bleeding.

The reason for this lack of association between improved pre-PCI patency and improved clinical outcomes is not clear. It could be speculated that the arteries were closed too long for early opening to be of benefit. Early opening of an artery that ends in a swollen and edematous capillary bed is likely to be of little use. In ASSENT 4, pre-PCI lysis tended to perform better among patients who presented early and had non-organized clot that was still susceptible to lysis. Thus, the results stratified by duration of symptoms will be of ongoing interest.

Other hypotheses to explain the lack of benefit of lysis include the possibility that pre-PCI lysis may enhance reperfusion injury or that it may be associated with intra-myocardial hemorrhage.

One future trial, the STREAM trial, is planned to again evaluate pre-PCI lysis.

TNK administered via the intracoronary route is also being evaluated to improve microcirculatory function following primary PCI.