Atlanta, GA - The GP IIb/IIIa blocker abciximab reduces adverse events in patients with high-risk non-ST-segment-elevation ACS undergoing PCI even after pretreatment with 600 mg of clopidogrel, but the benefits are confined to patients presenting with an elevated troponin level.

These are the main findings of the ISAR-REACT 2 trial, presented at the American College of Cardiology (ACC) 2006 Scientific Sessions today by Dr Adnan Kastrati (Deutsches Herzzentrum, Munich, Germany). The trial was published simultaneously online in the Journal of the American Medical Association [1].

Introducing his presentation, Kastrati noted that his previous trials (ISAR-REACT and ISAR SWEET) have shown that abciximab is not necessary in elective PCI if patients are pretreated with 600 mg of clopidogrel, but this question has so far not been studied in high-risk ACS patients undergoing PCI.

The ISAR REACT-2 study included 2022 such patients, who were all given clopidogrel 600 mg at least two hours before the procedure, as well as 500 mg of oral or intravenous aspirin. In the cath lab they were randomized to abciximab or placebo.

Results showed that the primary end point—a composite of death, myocardial infarction, or urgent target vessel revascularization (TVR) at 30 days—was significantly reduced in the abciximab group.

ISAR-REACT 2: Main efficacy results at 30 days

End point	Abciximab (%)	Placebo (%)	RR (95% CI)
Death/MI/urgent TVR*	8.9	11.9	0.75 (0.58-0.97)
Death	1.1	1.6	0.69 (0.32-1.47)
MI	8.1	10.5	0.77 (0.59-1.02)
Urgent TVR	1.0	1.2	0.83 (0.36-1.92)

Subgroup analysis showed that among patients without an elevated troponin level, there was no difference in the incidence of primary end point between the two groups, but among patients with an elevated troponin level, the incidence of events was significantly lower in the abciximab group.

ISAR-REACT 2: Death/MI/urgent TVR according to troponin level

Troponin level	Abciximab (%)	Placebo (%)	RR (95% CI)
>0.03 µg/L	13.1	18.3	0.71 (0.54-0.95)
<0.03 µg/L	4.6	4.6	0.99 (0.56-1.76)

There were no significant differences between the two groups regarding the risk of major and minor bleeding as well as need for transfusion.

ISAR-REACT 2: Bleeding results

Outcome	Abciximab (%)	Placebo (%)	RR (95% CI)
Major bleed	1.4	1.4	1.00 (0.50-2.08)
Minor bleed	4.2	3.3	1.27 (0.81-1.99)
Transfusion	2.5	2.0	1.25 (0.70-2.23)

In an accompanying editorial [2], Drs Steven Steinhubl and Richard Charnigo (University of Kentucky, Lexington) say: "Given current evidence, all heparin-treated patients undergoing PCI for treatment of ACS with elevated troponin levels should receive adjunctive GP IIb/IIIa antagonists, irrespective of whether the patient has also received adequate pretreatment with clopidogrel. Whether there is additional clinical benefit to administering clopidogrel in addition to a GP IIb/IIIa antagonist, as has been suggested by previous post hoc analysis, remains to be prospectively studied."

They add that several new agents are also now being tested, including new thienopyridines (prasugrel), reversible oral (AZD6140) and parenteral (cangrelor) P2Y12 inhibitors, as well as platelet thrombin receptor inhibitors (SCH530348), adding that these new agents "may cloud the picture again, but at the same time may also lead to continued improvements in the care of patients with acute coronary disease."

But what about ACUITY?

The results of ISAR-REACT 2 were reported at the ACC the day after the ACUITY trial, which studied a similar population of patients and suggested that GP IIb/IIIa blockers were not needed if bivalirudin was used as the antithrombotic agent instead of heparin. So the obvious question now is: "What are the implications of these two trials together?" This will be discussed in a subsequent article on theheart.org.