CICERO: Mixed Results for Intracoronary Abciximab in STEMI

November 16, 2010

November 16, 2010 (Chicago, Illinois) — Intracoronary administration of abciximab (ReoPro, Eli Lilly) compared with intravenous administration did not improve myocardial reperfusion as assessed by ST-segment resolution but did improve myocardial reperfusion as assessed by myocardial blush grade and a smaller enzymatic infarct size in STEMI patients undergoing primary PCI with thrombus aspiration in the CICERO study.

But designated discussant of the study at the American Heart Association (AHA) 2010 Scientific Sessions, Dr Michael Lincoff (Cleveland Clinic, OH), said that any benefits suggested in the intracoronary group may have been caused by a better baseline infarct artery patency in the intracoronary patients.

The study has also been published online November 15, 2010 in Circulation to coincide with the AHA presentation.

Presenting the study at the AHA meeting, Dr Youlan Gu (University Medical Center Groningen, the Netherlands) explained that the GP IIb/IIIa blocker abciximab is an effective adjunctive treatment strategy during primary PCI for STEMI, and several small studies have suggested beneficial effects of intracoronary over intravenous administration. The CICERO trial was conducted to evaluate intracoronary abciximab in a larger population.

In the study, 534 STEMI patients undergoing primary PCI with thrombus aspiration within 12 hours of symptom onset were randomized to either an intracoronary or an intravenous bolus of abciximab (0.25 mg/kg). Patients were pretreated with aspirin, heparin, and clopidogrel.

Largest Intracoronary Trial to Date

Gu reported that the CICERO trial is the largest clinical trial to date to determine the effect of intracoronary vs intravenous administration of abciximab in STEMI patients undergoing primary PCI, and this is the first medium-scale trial performed in a contemporary cohort of STEMI patients treated with manual thrombus aspiration.

Results showed that the primary end point--the incidence of restored myocardial reperfusion, defined as complete ST-segment resolution--was similar in the intracoronary and intravenous groups. However, the secondary end points of myocardial reperfusion as assessed by myocardial blush grade and infarct size (in the subset of evaluable patients) were improved in the intracoronary group. The incidence of major adverse cardiac events at 30 days was similar in both groups, but the trial was not powered to show a difference in clinical outcomes.

CICERO: Major Results

Outcome Intracoronary abciximab Intravenous abciximab p
Complete ST-segment resolution (%)  64   62 0.56
Myocardial blush grade 2/3 (%)  76   67 0.02
Mean enzymatic infarct size (creatine kinase levels, U/L) 1214  1746 0.008
Major adverse cardiac events (%) 5.5   6.1 0.79

Infarct size was similarly reduced, by about 30%, when measured by either creatine kinase-MB or cardiac troponin T.

There were no adverse procedural events related to intracoronary abciximab administration. The incidence of in-hospital major and minor bleeding was low and similar between the intracoronary and intravenous groups.

Discussant Not Impressed

In his discussion of the trial, Lincoff highlighted the difference in baseline TIMI grade 2/3 flow between the two groups (45% in the intracoronary group vs 33% in the IV group, p=0.05). "This difference would be expected to be associated with a reduction in infarct size on its own and therefore biased the study toward the intracoronary group," he noted.

Lincoff also pointed out that when the patients with blush grade 2/3 were separated out into grade 2 and grade 3, it showed that the grade 3 results were almost identical (34% for intracoronary vs 33% for IV), and "it is only really grade 3 that predicts outcomes." He also questioned why cardiac enzymes were reported in only 46% of patients.

He further suggested that the evidence supporting a benefit of even intravenous abciximab in STEMI was "not overwhelming" and that the field is tending to move away from GP IIb/IIIa blockers toward bivalirudin (Angiomax, the Medicines Company) instead.

Better Adjunctive Therapy May Explain Results?

In the Circulation paper, Gu et al point out that a previous smaller trial suggested higher rates of ST-segment resolution with intracoronary than with intravenous abciximab, but its patient population appeared to be at a higher clinical risk than in the current study and had a lower use of clopidogrel preloading and thrombus aspiration. "Therefore, it is possible that the benefit of intracoronary administration on myocardial reperfusion was offset by a lower clinical risk and the routine use of thrombus aspiration in the present study," they write.

They further comment that the discrepancy between myocardial reperfusion as assessed by ST-segment resolution and myocardial blush grade is unexpected, as these measures are usually consistent in both positive and negative studies and in previous studies reporting on intracoronary abciximab.

One reason for this discrepancy may be that the two measurements represent different pathophysiological phenomena--while blush grade reflects mechanical patency of the microvasculature, ST-segment resolution may reflect the functional status of the myocardial cells. They point out that both markers of reperfusion have independent prognostic value in predicting long-term mortality, although the prognostic value of ST-segment resolution has been debated in patients treated with primary PCI.

A second possible reason for the discrepancy is that the two markers are assessed at different time points after primary PCI: blush grade is measured immediately after PCI, while ST-segment resolution is measured at 30 to 60 minutes after PCI, and it may be that the beneficial effect of intracoronary administration on myocardial reperfusion is present immediately after PCI but not 30 to 60 minutes later.

The researchers conclude that further trials are needed to evaluate whether intracoronary administration of abciximab during primary PCI improves clinical outcome, and they note that a few such trials are ongoing.

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