Abstract & Commentary
By Andrew D. Perron, MD, FACEP, FACSM, Residency Program Director, Department of Emergency Medicine, Maine Medical Center, Portland, ME.
Source: De Luca G, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: A meta-analysis of randomized trials. JAMA 2005; 293:1759-1765.
The treatment of ST-segment elevation myocardial infarction (STEMI) continues to evolve at a rapid pace, particularly with the continuing development of adjunctive treatments to aid in reperfusion. While both fibrinolysis and mechanical reperfusion strategies (e.g. primary angioplasty) are clearly beneficial, suboptimal results may occur after reperfusion due to distal platelet embolization or platelet aggregation on reperfused endothelium. The glycoprotein (GP) IIb/IIIa inhibitors are designed to address and inhibit this process. While benefit has been shown in some studies when treatment is coupled with mechanical reperfusion, the effect of GP IIb/IIIa inhibitors on overall patient outcome remains controversial.
The purpose of this study was to perform a comprehensive meta-analysis of all randomized trials with abciximab as adjunctive treatment of STEMI, including both fibrinolytic and mechanical reperfusion strategies. This meta-analysis covered the years 1990-2004, and included 11 trials involving 27,115 STEMI patients. The primary outcomes assessed were 30-day mortality, long-term mortality (i.e., 6-12 months), 30-day re-infarction rate, and bleeding incidence.
The study findings demonstrated a significant reduction in short-term (2.4% vs 3.4%, p = 0.047) and long-term (4.4% vs 6.2%, p = 0.01) mortality in patients treated with abciximab and undergoing primary angioplasty vs controls. Significantly, such an association was not found when abciximab was combined with fibrinolysis. Abciximab was associated with reduced 30-day re-infarction rates in both groups (2.1% vs 3.3%, p < 0.001). Finally, abciximab did not result in increased episodes of intracranial or major bleeding when combined with primary angioplasty (4.7% vs 4.1%, p = 0.36), but was associated with these complications when combined with fibrinolysis vs controls (5.2% vs 3.1%, p < 0.001). Notably, this was true even when the studies using reduced-dose fibrinolytics were analyzed.
The authors concluded that there are sufficient aggregate data for use of abciximab as adjunctive treatment to primary angioplasty (reduces 30-day mortality and re-infarction rates, as well as long-term mortality without increased risk of major bleeding). They also concluded that abciximab cannot be recommended as adjunctive treatment to fibrinolysis as it confers no difference to short or long-term mortality benefit, but does increase the incidence of significant bleeding.
Commentary
Practicing at a tertiary care medical center, I have the luxury of 24-hour cardiac catheterization laboratory availability, cardiology fellows, and smart residents who challenge me to keep current on myriad topics. For its part, the faculty tries to keep in mind that most of our graduates who complete the program won’t be practicing in such an environment. In our ED, STEMI patients embark on a set clinical pathway from the moment they enter the door until they have (hopefully) TIMI-3 blood flow through the culprit artery a very short time later. Abciximab is given by the nursing staff as part of this pathway, just as nitroglycerin, oxygen, and heparin are. My warning to residents is to not get too comfortable with these clinical pathways, as they may not be there when they get out in the real world.
The use of abciximab in our STEMI pathway is a perfect case in point. Because we use primary angioplasty in more than 95% of our STEMI patients, residents may never have the opportunity to give thrombolytics to a patient during their residency. If they subsequently join a practice where fibrinolysis is the reperfusion modality of choice, they may combine their treatment experience with that reperfusion strategy, potentially resulting in patient harm.
This study is useful for two reasons. First, it confirms the relative benefit of GP IIb/IIIa inhibitors as adjunctive treatment with primary angioplasty in an enormous patient population. The benefits are not huge, but I personally would prefer the smaller short and long-term mortality rates over the alternative, especially since bleeding does not seem to be increased with this strategy.
Second, it also clearly demonstrates no added benefit of such adjunctive treatment if fibrinolysis is utilized. Again, on a personal level, if I have a STEMI and am going the lytic route, I would not want a GP inhibitor to be used on me, as it confers no survival advantage but adds to my major bleeding potential.
The purpose of this study was to perform a comprehensive meta-analysis of all randomized trials with abciximab as adjunctive treatment of STEMI, including both fibrinolytic and mechanical reperfusion strategies.
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