Zwolle, the Netherlands - A new meta-analysis suggests that the GP IIb/IIIa blocker abciximab (ReoPro®, Centocor, Eli Lilly) is beneficial in MI patients undergoing primary angioplasty, but not in those receiving fibrinolysis.[1]

The new analysis, published in the April 13, 2005 issue of the Journal of the American Medical Association, included 11 published randomized trials of abciximab vs controls in a total of 27 115 STEMIpatients. Results showed that abciximab was associated with a significant reduction in 30-day and long-term mortality in patients treated with primary angioplasty, but not in those receiving fibrinolysis. The 30-day reinfarction rate was significantly reduced with abciximab in patients treated with either fibrinolysis or primary angioplasty, but this benefit was offset in fibrinolysis patients by an increased risk of major bleeding complications.

The authors, led by Dr Giuseppe De Luca (Hospital de Weezenlanden, Zwolle, the Netherlands), point out that more information on the use of abciximab in MI patients will come from two large randomized studies currently under way (CARESS and FINESSE), but that until these results are available, they recommend: "Abciximab should be strongly considered in primary angioplasty for STEMI, particularly in high-risk patients, whereas the combination of abciximab and fibrinolysis should be avoided due to the observed higher risk of bleeding complications, particularly in elderly patients."

In the introduction section of the paper, the researchers note that the effect of GP IIb/IIIa blockerson outcomes in patients with STEMI remains controversial. Previous meta-analyses have been restricted to primary-angioplasty trials and have failed to include all randomized trials, they say. Since only a few small trials have been conducted on tirofiban and eptifibatide, they performed a comprehensive meta-analysis of all randomized trials with abciximab as adjunctive therapy in treatment of STEMI.

Of the 11 trials included, three were in fibrinolysis studies, which involved 23 166 patients (85.3% of the entire meta-analysis), and the remaining eight trials were conducted in 3 949 patients undergoing primary angioplasty. In all the fibrinolysis trials, full-dose abciximab was given with half-dose fibrinolytic therapy.

Results showed that both short- and long-term mortality was improved with abciximab in patients undergoing primary angioplasty but was unchanged in the fibrinolysis group. In addition, the fibrinolysis group showed a significant increase in major bleeding with abciximab, whereas the primary-angioplasty group did not.

The authors estimate that in the setting of primary angioplasty, treatment of 100 patients with abciximab would prevent one death at 30-day follow-up and treatment of 56 patients would prevent one death at long-term (6-12-month) follow-up.

In terms of reinfarction, they estimate a number needed to treat of 83.3 in all trials combined, 111.1 in primary-angioplasty trials, and 76.9 in fibrinolysis trials to prevent one reinfarction at 30 days. However, in the fibrinolytic studies, treatment of 48 patients would produce one extra major bleed.

One of the coauthors of the current meta-analysis, Dr Harry Suryapranata (Hospital de Weezenlanden), told heartwire that he believes the GP IIb/IIIa blockers will be particularly useful in the prehospital treatment of STEMI patients who will go on to receive primary PCI.

He was one of the investigators in the ON-TIME study, which showed that prehospital administration of another IIb/IIIa blocker, tirofiban, gave an improvement in TIMI-2/3 flow and lower thrombus burden at the time of PCI.

Suryapranata pointed out to heartwire that 41% of the ON-TIME patients were enrolled in the ambulance. He added that the practice of giving a IIb/IIIa blocker in the ambulance has already been implemented in the Zwolle region, where patients are then taken directly to the cath lab for primary PCI.

But he says he can see no role for a IIb/IIIa blocker with fibrinolysis. "The future of IIb/IIIa blockers in STEMI patients is early administration before primary PCI. I don't see a future for these agents with fibrinolysis because of the bleeding risk," he commented.

Use of prehospital abciximab before primary PCI is being investigated in the FINESSE trial, which has three arms: no early treatment; early abciximab; or early abciximab plus reteplase. All patients will then undergo PCI. The no-early-treatment patients will still receive abciximab at the time of the PCI procedure

Suryapranata commented to heartwire that he was surprised that FINESSE was randomizing to abciximab plus reteplase, as he thought that this combination was now undesirable because of the bleeding risk.

Dr Eric Topol (Cleveland Clinic, OH), who is coordinating the FINESSE trial and was also an investigator in the current abciximab meta-analysis, told heartwire that he understood the concern. But he added, "The reteplase plus abciximab arm is being carefully reviewed by the [data safety monitoring board], and to date there is no indication that there is any safety or efficacy imbalance in the trial."

Suryapranata also believes that a IIb/IIIa blocker would be better than fibrinolysis alone (which is also being investigated in other trials) as prehospital treatment before PCI. "The fibrinolysis-followed-by-PCI strategy was investigated during the 1980s without success. And I just have a bad feeling about it," he commented to heartwire.