Plaque sealing—a concept waiting for support

The progress that has been observed in all areas of percutaneous coronary interventions (PCI) has failed to materialize in substantial decreases in mortality in patients treated percutaneously. Normalizing the blood flow in significant stenoses addresses ischemia and its symptoms but does not alter the prognosis (1). The latter is influenced by the vessel closures that occur not only in the hemodynamically significant but also in the nonflow-limiting lesions (1,2). The individual risk of a stenosis to occlude after plaque rupture is related to its severity (3). Nevertheless, non-significant stenoses are in certain, even if smaller, risk for closure and infarction (1). Since there are usually many more mild lesions, the majority of the infarctions occur from non-significant lesions. Little et al. showed in a pivotal paper published 17 years ago, that many non-critical coronary lesions can produce myocardial infarction (2). This observation has been used to support the concept of plaque sealing by coronary interventions either by balloon angioplasty alone or by stenting (4,5). The working hypothesis of this phenomenon has two cornerstones (1). First, a coronary stenosis subjected to PCI will not progress to a total occlusion except if it closes abruptly. The second element of the plaque sealing concept is that even if restenosis occurs, neoinitimal tissue almost precludes endothelial rupture and thrombosis (1,6). As a result, plaque sealing, by preventing plaque rupture, will prevent thrombosis and thus myocardial infarction and death. Despite its theoretical attractiveness, the plaque sealing principle has not been universally accepted for various reasons. The first is that such strategy failed to show any advantage over the current interventional practice (treating lesions with w50% diameter stenosis) (4,7). On the contrary, previous data have shown that stent implantation for narrowingsv50% in diameter are subject to an increased rate of major adverse cardiac events and thus the risk outweighs any hypothetical long-term benefit. In a recently published study, including a total of 3812 patients pooled from 14 different studies of angioplasty alone and stenting, the combined event rate (death, non-fatal myocardial infarction, and repeat revascularization) when angiographically nonsignificant stenoses were treated was over 20% at one year follow-up (7). It is worth noting that the event rate after PCI was not related to stenosis severity (7). Moreover, in the Coronary Artery Surgery Study (CASS) registry, the estimated one-year probability of an anterior myocardial infarction in left anterior descending lesions with a diameter stenosisv50% was 0.6% and with diameter stenosis between 50% and 70% was 2.2% (3). These rates when compared, even if indirectly, to the rates reported in the study of Mercado et al., are significantly lower (7). Similarly, the Deferral Versus Performance of PTCA in Patients without Documented Ischemia (DEFER) trial showed that there is no clinical benefit of PCI for non-significant stenoses at two years (8). In the same direction were the results of previous studies that addressed the same issue (4,6). Originally, the concept of plaque sealing was intended to be applied with balloon angioplasty alone, which is no longer realistic after the dominance of stenting during PCI in the mid to late 1990s (5). Therefore, the concept was extended to the use of stents that appear more suitable for this purpose. However, bare metal stents have a yearly event rate that surpasses 20% even if not implanted on angiographic critical lesions (7). Sirolimuseluting stents and polymer-based paclitaxel-eluting stents have been shown to decrease significantly late events mainly due to the reduction of repeat revascularization (9–13). Nevertheless, data are limited regarding the use of drug-eluting stents in non-significant lesions. In this issue of the journal,