Author + information
- Salvatore Brugaletta, MD, PhD∗ ( and )
- Manel Sabate, MD, PhD
- Cardiovascular Institute, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- ↵∗Address for correspondence:
Dr. Salvatore Brugaletta, Cardiovascular Institute, Hospital Clínic; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Carrer de Villarroel, 170, 08036 Barcelona, Spain.
Percutaneous coronary intervention with stent implantation is currently widely used in many anatomical and clinical situations, such as long lesions, chronic total occlusions, saphenous vein grafts, restenotic lesions, acute myocardial infarction, bifurcation, and left main disease (1). This increased use has become possible thanks to new and better stent designs, improvements in stent implantation technique, effective antiplatelet therapy, and many trials demonstrating stent safety and efficacy (1).
Nevertheless, small coronary vessels still remain a lesion subset in which drug-eluting stents (DES) remain associated with relatively high restenosis rate (2). Of note, very few data are currently available in this setting, namely because reference vessel diameter <2.25 mm represents a classic exclusion criterion of all stent clinical trials either because DES did not have such small size available or because small coronary vessels PCI encompasses many difficulties, such as guidewire manipulation, lesion and device crossing, tortuosity, risk of dissection, perforation, and abrupt closure. Small coronary vessel disease is also frequent in patients with multiple comorbidities, such as renal impairment and diabetes, and for this reason, even after successful procedure, its long-term outcomes are still affected by high rate of restenosis and thrombosis (3).
Definition of small coronary vessels has also evolved over the years. Early percutaneous coronary intervention trials progressively identified small-vessel treatment as vessels ≤2.9 mm (4), <2.80 mm (5), or ≤2.75 mm in diameter (6). A recent study has suggested that with current stents, a vessel diameter <2.5 mm is a suitable threshold to identify small target vessels (7). The progressive reduction of this threshold is probably due to progressive increase in DES efficacy and safety in smaller coronary vessels up to 2.25 mm.
It is also important to remember that for percutaneous treatment of such small coronary vessels, bare-metal stents have so far been the only ones available in such small size, and they were used at the expense of high restenosis rate. Implantation of an oversized 2.25-mm DES for a 2.0-mm vessel may indeed risk perforation, distal dissection, or, if the stent is implanted below nominal pressure, malapposition or underexpansion with subsequent risk of stent thrombosis. Use of drug-eluting balloons (DEBs) has also been explored, as it may provide significant theoretical advantages over DES in this anatomical subset such as low-risk of stent thrombosis, shortened duration, and less dependence on dual antiplatelet therapy. DEBs have indeed shown a better late loss as compared with paclitaxel-eluting stents in the BELLO (Balloon Elution and Late Loss Optimization) trial (0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm; p = 0.001). The problem was that in up to 20% to 30% of patients receiving DEB bailout bare-metal stent implantation was needed (8). For all these reasons, a DEB was seen as an adjunctive tool to DES in such small vessel size, but not as a substitute, and is not currently available in the United States.
Given these considerations, as interventional cardiology is fast evolving and more complex coronary artery disease is currently treated as compared to years ago, some industries have eventually started to develop dedicated DES for very small coronary vessels (2.0 mm in diameter) to satisfy this unmet need, helped also by the technological improvement in stent material that allows thin struts. A particularly thin strut is indeed needed in small coronary vessels not only to reduce risk of restenosis, but also to avoid creating a late loss due to the presence of the stent: a stent of 100-μm thickness would cause, for instance, a circumferential loss of 0.2 mm only due to its implantation, which is relatively much more important in a 2.0 mm in diameter vessel than in a larger vessel (9).
In this issue of JACC: Cardiovascular Interventions, Price et al. (10) report the first findings on the performance of a DES specifically designed for very small coronary vessels. This is a prospective, single-arm study testing the Resolute Onyx (Medtronic Cardiovascular, Inc., Santa Rosa, California) 2.0 mm zotarolimus-eluting stent having target lesion failure (TLF) as the primary endpoint. Of note, within the inclusion criteria are a reference vessel diameter ≥2.0 mm and <2.25 mm and a lesion length ≤27 mm, and a subset of subjects who underwent angiographic follow-up at 13 months. A total of 101 subjects with 104 lesions were enrolled into the study, with 47% being diabetic patients. Lesions included were located in small vessels, with a reference vessel diameter of 1.91 ± 0.26 mm. TLF at 12 months was 5.0% and late lumen loss was 0.26 ± 0.48 mm with 12.0% of binary restenosis and without a signal for stent thrombosis.
The findings of this study currently represent the first available data on the real performance of DES specifically designed for treatment of very small coronary lesions. This is something much needed, as we cannot rely on the fact that these small stents follow the performance of their “big brothers” in larger vessels. Data from other stents designed for very small coronary lesions also would be needed.
Nevertheless, some points should be highlighted to interpret these results well. First of all, some patients' selection for angiographic follow-up cannot be excluded due to lack of randomized selection, although the authors claim no differences in terms of clinical and procedural characteristics between those patients who were included and those patients who were not. Moreover, we should ask ourselves if late loss in these small vessels is a good surrogate angiographic endpoint, as the same stent thickness may create some late loss, which is relatively more important in small than in large vessel size. This together with a supposed low acute gain (which is not reported in the study) could explain the significantly high rate of angiographic binary restenosis found in this present analysis (12%).
When we talk about small coronary lesions, we always think about diabetic patients who had lesions not only located in small vessels, but that are also long. In the present paper, although diabetic patients were quite well represented and lesions were indeed located in small vessels, lesions treated were particularly short (mean length of 12.6 mm). This could limit the applicability of these data in daily clinical practice where coronary lesions in small vessels are usually longer.
Last, but not least, sample size calculation of this registry may not deliver a useful clinical message. The authors considered an expecting TLF rate of 9.4%, compared with a performance goal of 19%. This goal was chosen arbitrarily looking at same thresholds chosen in previous studies testing 2.25 mm DES, which showed that TLF rate in small vessels was much better than expected (11,12). The choice of a performance goal set approximately twice the point estimate of the expected TLF rate, knowing that DES performance is already better than expected, seems therefore an easy win for any kind of stent and may reduce the clinical value of the present results. A comparator arm, such as DEB or simple, plain old balloon angioplasty, with a no-inferiority or even superiority design, would have had a more meaningful clinical message, showing that vessel size does not matter in terms of stent performance. Studies with longer follow-up would also be needed to exclude the so-called late catch-up phenomenon in such small coronary vessels.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Brugaletta has received institutional research grant support from AstraZeneca; and speaker fees from Abbott Vascular and Boston Scientific. Dr. Sabate has reported that he has no relationships relevant to the contents of this paper to disclose.
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