NEW YORK (Reuters Health) Pooled data from four relatively small but high-quality prospective randomized controlled studies suggest an advantage to intracoronary (IC) over intravenous (IV) administration of abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (pPCI).
This is particularly the case for patients with higher-risk profiles, note Dr. Yuichi J. Shimada and colleagues from Beth Israel Medical Center, University Hospital and Manhattan Campus for the Albert Einstein College of Medicine in New York City.
But Dr. Peter Riis Hansen, from Gentofte University Hospital, Hellerup, Denmark, who was not involved in the current analysis, believes the IV route should remain the standard of care.
Abciximab, a glycoprotein IIb/IIIa receptor inhibitor, has been shown to improve outcomes in the setting of STEMI and pPCI. Yet, there is a great deal of uncertainty as to the optimal route of administration, Dr. Shimada and colleagues note in a report online December 7 in the American Journal of Cardiology.
Clinical trials to date have yielded conflicting results. A previous meta-analysis published in 2010 by Dr. Hansen’s group suggested favorable effects of IC over IV abciximab in patients with acute coronary syndromes. But this analysis was limited due to the heterogeneity of the studies, Dr. Shimada and colleagues say.
Recently, two other trials have been published. The CICERO trial found mixed results for IC versus IV abciximab (see Reuters Health report Nov 30, 2010) and the EASY-MI trial did not find an advantage of IC administration (see Reuters Health report April 29, 2010).
At publication of the EASY-MI trial results, Dr. Olivier Bertrand of the Quebec Heart Lung Institute, who led the study, told Reuters Health: “Despite its appeal, I do not think there is much future” for intracoronary delivery.
The recent publication of these two additional randomized controlled trials prompted Dr. Shimada and colleagues to reanalyze the totality of the data in a more thorough fashion.
In addition to the CICERO and EASY-MI trials, they included two other prospective randomized trials; altogether, 1,148 patients participated in the four trials, of whom 586 were randomized to IC abciximab groups and 562 to IV abciximab groups.
Collectively, there were 9 (1.5%) deaths in the IC groups and 20 (3.6%) in the IV groups. A significant reduction in death was noted with IC compared with IV abciximab (odds ratio 0.44; P = 0.04). The mortality data were homogenous and showed no significant variation among the studies, the authors note, and there was no significant publication bias.
During follow-up, major adverse cardiovascular events (MACE) occurred in 35 (6.0%) patients in the IC group and in 58 (10.3%) patients in the IV group. Significant heterogeneity among the studies for this outcome was seen and the overall analysis did not show a significant reduction in MACE with IC compared to IV abciximab (odds ratio 0.59; P = 0.18).
However, a significant reduction in MACE was seen in a subgroup of studies in which most patients did not receive aspiration thrombectomy (6.1% vs 16.2%; odds ratio 0.33; P = 0.0004).
Overall, our results suggest that patients with higher risk profiles such as longer ischemia duration and higher thrombus burden benefit most from IC administration compared to the IV route, Dr. Shimada and colleagues note in their report.
In comments to Reuters Health, Dr. Hansen cautioned that meta-analyses are subject to limitations and they do not, of course, add up to the evidence level of results from adequately powered randomized controlled trials.
In this regard, he noted that the large CICERO trial was negative in terms of the primary end point (myocardial reperfusion determined by ST segment resolution).
And to my mind, the negative results of the even larger AIDA-STEMI trial (n = 2,065) published in abstract form at the recent American Heart Association meeting put one more nail in the coffin of IC administration, he added.
AIDA STEMI was not included in the current meta-analysis and more studies are ongoing.
It remains possible, that IC administration may incrementally improve selected surrogate endpoints in selected STEMI patient groups, but this is unlikely to be of clinical significance, Dr. Hansen said.
In short, I believe that now we should move on and that IV abciximab should remain the standard of care, he concluded.
Reference:
Am J Cardiol. 2011. Published online December 7, 2011.
