Resolute‚Ñ¢ Drug-Eluting Stent: A Resolution for Bifurcation Lesions?

The treatment of coronary artery bifurcation lesions remains one of the most challenging lesion subsets in interventional cardiology because of a low success rate, a relatively high incidence of procedural complications, greater restenosis rates and a higher risk of stent thrombosis. The introduction of multiple approaches to treat such lesions, including double-wire and kissing-balloon angioplasty, directional and rotational atherectomy, and most recently the convoluted deployment of multiple stents, have done little to ameliorate the lower procedural success rates and worse clinical outcomes seen in these types of lesions.¹

Bifurcation geometry (the angle between the main branch and the side branch), assessment of lesion severity, vessel location, bifurcation classification, type of stent, stenting technique and residual stenosis are some of the important issues that need to be considered when dealing with a bifurcation lesion.² The introduction of drug-eluting stents (DES) has resulted in lower event rates and a reduction in main-vessel restenosis; however, side-branch ostial residual stenosis, long-term restenosis and stent thrombosis still remain a problem.³ Recent studies have shown that there is no long-term benefit from systematic intervention of the side branch and, actually, it is associated with increased radiation dose and periprocedural enzyme leak. In view of these issues, the current recommended stenting strategy in coronary bifurcation lesions is the provisional side-branch stenting strategy where the main vessel is stented and the side branch is only treated with stent implantation in cases of significant residual stenosis after stenting the main vessel.⁴ A recent meta-analysis of six randomized, controlled studies has shown that the use of a single-stent strategy with provisional stenting of the side branch yielded similar rates of death, restenosis or stent thrombosis at 1-year follow up compared to a two-stent strategy. However, myocardial infarction rates were significantly lower in patients randomized to a provisional single stent in the main branch strategy (Figures 1 and 2).⁵ While DES have reduced restenosis rates in the main vessel of bifurcating lesions, long-term restenosis in the side branch remains a concern. Resolute™ (Medtronic, Inc., Minneapolis, Minnesota) is a next-generation zotarolimus-eluting stent system designed to match the efficacy and safety of the Endeavor™ stent (Medtronic), while improving outcomes in more complex lesions.⁶ The Resolute stent platform is a low-profile, thin-strut Driver^® bare-metal stent (Medtronic) with the antiproliferative agent zotarolimus. The phosphorylcholine coating of the Endeavor stent has been replaced by a BioLinx™ tri-polymer coating to extend drug elution to match the potentially delayed arterial healing time associated with treatment of complex lesions.⁷ This stent has been associated with lower in-stent late lumen loss and a minimal amount of neointimal hyperplasia.⁸ The BioLinx polymer is the first designed specifically for DES. The polymer is a combination of three different polymers; a hydrophilic C19 on the abluminal surface, a hydrophobic C10 polymer coating the stent itself, and a water-soluble polyvinyl pyrrolidinone polymer to increase initial drug burst and enhance biocompatibility.⁹ Combined, these three polymers allow for a more gradual and controlled release of zotarolimus over a longer period of time.⁶ In the porcine model, 85% of the zotarolimus content elutes into tissue during the first 60 days post procedure, and the remainder of the drug has completely eluted by 180 days.⁸ The safety and effectiveness of the zotarolimus-eluting stent was assessed in the RESOLUTE trial.¹⁰ In this study, a total of 2,292 patients were randomly assigned to receive either zotarolimus-eluting stents or everolimus-eluting stents. The composite of death from cardiac causes, any myocardial infarction or target-lesion revascularization occurred in 92 patients (8.2%) in the zotarolimus-stent group, and 94 patients (8.3%) in the everolimus-stent group. The only difference was the rate of stent thrombosis: at 1 year, 13 (1.2%) definite stent thromboses had occurred in the zotarolimus-stent group, as opposed to just 3 (0.3%) in the everolimus-eluting stent (p = 0.01).¹⁰

In this issue of the Journal, Tommasino and colleagues assessed the use of the zotarolimus-eluting Resolute stent in a series of 180 consecutive patients with unselected bifurcated lesions.¹² Three Italian centers participated in this prospective, multicenter, nonrandomized trial. The results are noteworthy, given that they were obtained in a complex, all-comers, nonselected patient population with coronary artery bifurcation lesions. Attesting to the high-risk angiographic characteristics of these patients, the target lesion was located in an unprotected left main in 16.7% of patients and on the left anterior descending/diagonal branch bifurcation in 52.2%. Interestingly, a high percentage of these patients required rewiring of the side branch (74.4%), and this was successful in 133/134 patients. Overall procedural success was 98.3%, and at 9-month follow up, the major adverse cardiac events rate was 2.2%, driven by 1 cardiac death and 3 cases of target-vessel revascularization. Therefore, in this population of all-comers, the use of a provisional approach for the treatment of bifurcation lesions with the zotarolimus-eluting Resolute stent was associated with excellent procedural results and promising clinical outcomes.

This study is limited by the lack of randomization and of a control group to compare procedural and clinical results. Although this stent is promoted as having a low rate of in-stent late lumen loss, quantitative coronary angiography analysis was not done to assess true restenosis rates. Finally, the clinical follow up of only nine months’ duration was relatively short, which may also have an impact on restenosis or stent thrombosis rates. Whether this stent will be the stent of choice for bifurcation lesions remains to be proven as new players with dedicated bifurcation stents are being investigated in clinical studies. Although the Resolute stent showed excellent procedural success and low rates of major adverse coronary events for unselected bifurcated lesions, based on the current available literature, provisional stenting should be regarded as the treatment strategy of choice and a two-stent approach should be reserved for those patients with a suboptimal result.

References

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