Letter by Agostini et al Regarding Article, “Stent Thrombosis Late After Implantation of First-Generation Drug-Eluting Stents: A Cause for Concern”

To the Editor:

We appreciated the thorough review of Camenzind et al¹ of late stent thrombosis in drug-eluting stents. Although we agree with their general message, we have concerns related to the hypothetical correlation purported by the authors between angiographic late lumen loss and clinical events, which is not evidence based.

In particular, Figure 2 is not based on scientific data; the authors cite as its reference only an editorial.² The J-curved relationship between late loss and clinical events is puzzling. Although some evidence exists that an increase in late loss leads to an increase in restenosis (evidence, however, that comes from analyses based also on bare metal stent data and thus not specific to drug-eluting stents), the hypothesized increase in death/myocardial infarction with negative late loss has never been proved. The relationships between late loss, restenosis, and clinical events are much more complex than shown in Figure 2; we actually do not even know if a relationship exists.^3,4 As a consequence, the statement that patients with negative late loss (as shown in Figure 3) are those with an increased risk of late stent thrombosis, and potentially of death/myocardial infarction, is totally misleading.

Late loss is a bidimensional parameter based on the difference of 2 minimal lumen diameters. These minimal lumen diameters are measured at different time points; thus, for 1 late loss value, 2 measures are exposed to the inherent 0.2-mm resolution limit of quantitative angiography. Even more important, each minimal lumen diameter can be measured in a different location of the coronary segment considered; minimal lumen diameter relocation, occurring between the measure performed immediately after stent deployment and at follow-up, is a frequent event and casts a light of caution on the value of late loss as surrogate end point.⁵

Although we share with the authors concerns related to the long-term data on drug-eluting stents, we should also bear in mind that the 2 most commonly studied drug-eluting stents, sirolimus- and paclitaxel-eluting stents, have shown similar rates of stent thrombosis but significant differences in late loss, with paclitaxel-eluting stents showing constantly greater late loss that sirolimus-eluting stents.

In conclusion, we already doubt the reliability of late loss as a surrogate for restenosis,^3–5 mainly when differences between devices are small (0.1 to 0.3 mm). Additionally, we believe that late loss should not be used as a surrogate for stent endothelialization and for late stent thrombosis in the absence of stronger than currently available evidence favoring this theory.