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Ischemic coronary syndromes and SVG Interventions—Do 2b/3a inhibitors miss the target?

The report in this issue of CCI by Kalyanasundaram and co-investigators [1] provides the most recent data analysis from the pivotal TARGET trial. This multicenter study intended to document clinical outcomes and identify their determinants in patients with ischemic syndromes who underwent PCI, mainly of native coronary arteries, with stenting and 2b/3a inhibition. The TARGET subgroup analysis of 200 SVG interventions by Kalyanasundaram and colleagues is interesting and its observations are relevant to clinical practice. Intriguingly, as the title of this editorial implies, a new conclusion can be drawn from their data. The patients received either tirofiban or abciximab without the use of distal protection. Multivariate analysis identified only thrombus as a predictor a 30-day major adverse coronary event. While no difference in outcome was noted between the two-receptor antagonists used in the SVGs, a previous report encompassing the entire TARGET population of 4,809 patients revealed that tirofiban offered less protection than abciximab [2]. The discrepancy between the results of these two reports could be attributed to the much smaller size of the SVG group. An important aspect needing focused evaluation is the commonly found large, multilayered thrombus in SVGs associated with impaired antegrade flow. Unfortunately, the investigators did not report detailed assessment of preand post-intervention thrombus burden and did not study the effect of different grades of thrombus burden on the yield of the 2b/3a antagonists and the MACE rate. A much desired QCA analysis by an independent core laboratory is absent. Other studies that used independent QCA core laboratory for this task found angiographic grading of thrombus burden [3] by interventionalists to correlate well with QCA thrombus assessment [4] and to assist in target lesion management. Despite an almost instinctive, prevailing belief among interventionalists in the necessity of protection devices to reduce adverse ischemic events, the lack of the protection devices in the TARGET study likely increased MACE rates. As the investigators and others have noted, morphologic characteristics unique for SVGs preclude application of protection devices. Furthermore, the absolute need to cross a tight, thrombotic lesion with a protection device is a limiting factor because crossing the thrombus and underlying plaque frequently causes distal embolization. Another concern is the deleterious effect of the deployed device on the wall of the SVG. The question of ‘‘why does a dedicated treatment with the useful 2b/3a inhibitors still leave thrombus as a major determinant of MACE?’’ becomes important. The answer lies with a proposed new conclusion from the TARGET reports: these pharmacologic agents ‘‘miss’’ the target thrombus. Studying the structural morphology of thrombi under scanning electron microscope demonstrates that elastic fibrin strands crisscross forming netlike scaffolding with platelets anchored to the fibrin. These elastic fibrin fibers consist of various sizes and exhibit marked resilience to external forces [such as balloon deployment] thereby fortifying the clot with structural support [5]. Blood cells, procoagulants, and vasoactive reactants are also present within the fibrin net. Because 2b/3a inhibitors exert their main selective effect only on the platelets receptors, they leave untouched the fibrin net and associated constituents. These uninterrupted components continue to constitute a flow barrier and serve as a substrate for further thrombus expansion and continuous mediators discharge. Previous studies have shown that in the presence of angiographic thrombus, 2b/3a inhibitors face an ‘‘efficiency ceiling’’ and do not contribute to a successful thrombus management and subsequent improvement in clinical results [6]. Therefore, inevitably, unless all major components of thrombus are engaged and targeted, throm-