Treatment of Coronary Bifurcations: Progress and Future

Coronary bifurcation lesions are a subset of complex coronary lesions that are encountered in 15%-20% of percutaneous coronary interventions.¹ Despite the advances in stent technology and catheter techniques, they present a formidable challenge to the interventional cardiologist because of inferior angiographic results and poor clinical outcomes compared with non-bifurcation lesions. 

Initial results with plain balloon angioplasty were suboptimal, with high rates of acute closure and restenosis of both the main and side branch.² Introduction of coronary stents virtually eliminated acute closure of the main vessel, but abrupt side-branch closure and restenosis of either branch persisted. The use of a two-stent strategy (main and side-branch stenting) was conceived to decrease side-branch closure and improve clinical outcomes, but the advantages were offset by high rates of restenosis compared to a one-stent strategy.³ 

The introduction of drug-coated coronary stents in the early 2000s, with the promise of reduced rates of restenosis, raised the possibility of improved outcomes in percutaneous intervention of bifurcation lesions. However, clinical outcomes after bifurcation stenting remain inferior to those in non-bifurcation lesions. High restenosis rates, particularly at the ostium of the side branch, are common, and this has been identified as the Achilles’ heel of percutaneous intervention of bifurcation lesions.² Focal stent underexpansion at the ostium, inadequate ostial scaffolding, and uneven drug distribution have been proposed to explain the high rates of restenosis after drug-eluting stent (DES) implantation. Even with DESs, a dedicated two-stent strategy to reduce restenosis and improve clinical outcomes has consistently been unsuccessful, with increased procedural complications and similar restenosis rates compared to provisional stenting of the side branch. In a pooled analysis⁴ of the landmark NORDIC I and BBC ONE bifurcation trials, a group of 457 patients underwent simple stenting and 456 patients underwent complex stenting with sirolimus- or paclitaxel-eluting stents. The composite endpoint at 9 months of all-cause death, myocardial infarction, and target vessel revascularization occurred in 10.1% of patients in the simple group vs 17.3% of patients in the complex group (hazard ratio, 1.84; 95% confidence interval, 1.28-2.66; P=.01). 

An additional concern with the use of first-generation DESs has been the risk of stent thrombosis. Treatment of bifurcations has been identified as an independent predictor for development of late stent thrombosis.⁵

More recently, newer second-generation DESs have become popular. The Resolute zotarolimus-eluting stent (R-ZES; Medtronic) is a thin-strut, cobalt-chromium, open-cell stent that releases the zotarolimus from a thin biocompatible coating. The stent’s new hydrophilic biocompatible polymer provides extended release of zotarolimus over approximately 180 days.⁶ This protracted drug release subdues neointimal proliferation and thereby lowers restenosis rates in comparison to older first-generation DESs. However, data relating to their performance in the treatment of coronary bifurcation lesions are limited. 

In this issue of the Journal of Invasive Cardiology, Ferenc et al⁷ report on the performance of the newer-generation Resolute zotarolimus-eluting stent in coronary bifurcation lesions compared to non-bifurcation lesions. They analyzed 3-year pooled data from the RESOLUTE All-Comers trial and the RESOLUTE international registry. R-ZESs were used in 2772 non-bifurcation lesion patients and 703 bifurcation lesion patients, of which 482 were treated with a simple stent technique (1 stent used to treat the bifurcation lesion) and 221 with a complex bifurcation technique (2 or more stents used). The primary endpoint was 3-year target lesion failure (TLF; defined as the composite of death from cardiac causes, target vessel myocardial infarction, or clinically indicated target lesion revascularization [TLR]), and was 13.3% in bifurcation vs 11.3% in non-bifurcation lesion patients (adjusted P=.06). Exploratory analysis revealed that this difference was driven by differences in the first 30 days between bifurcation vs non-bifurcation lesions (TLF: 6.6% vs 2.7%, respectively; adjusted P<.001). Between 31 days and 3 years, TLF, its components, and stent thrombosis did not differ significantly between bifurcation lesions and non-bifurcation lesions (TLF: 7.7% vs 9.0%, respectively; adjusted P=.50). 

These results suggest the possibility of an advancement of percutaneous treatment of bifurcation lesions. The rate of clinically driven TLR was significantly lower than historical controls and comparable to non-bifurcation lesions at long-term follow-up. The incidence of late stent thrombosis was also remarkably low, allaying concerns of stent thrombosis with DESs in bifurcation lesions. The results further lend support to the strategy of provisional side-branch stenting, as opposed to a dedicated two-stent strategy, in most bifurcation lesions to improve periprocedural outcomes. The 30-day risk of TLF in bifurcation lesions treated by the simple technique was 5.8%, which is less than in bifurcation lesions treated with the complex approach (8.2%; P<.01). Therefore, even with the use of improved second-generation DESs, a two-stent strategy is not superior and should be avoided as a first-line approach. 

Despite the better results with second-generation DESs in bifurcation lesions, our conventional approach to bifurcation PCI⁸ (with either single or double stents) has a number of limitations that include maintaining access to the side branch throughout the procedure, main-branch stent struts compromising the side branch, difficulty in rewiring the side branch or delivering the balloon/stent into the side branch through the stent struts, deformation of main-branch stent by side-branch dilatation, and inability to fully cover and scaffold the ostium of the side branch. Several stents have been specifically designed for bifurcations with the intention of addressing these shortcomings, and will hold the key to further success in PCI of bifurcation lesions. 

References

1. Sharma SK, Sweeny J, Kini AS. Coronary bifurcation lesions: a current update. Cardiol Clin. 2010;28(1):55-70.
2. Diletti R, Garcia-Garcia HM, Bourantas CV, et al. Clinical outcomes after zotarolimus and everolimus drug-eluting stent implantation in coronary artery bifurcation lesions: insights from the resolute all comers trial. Heart. 2013;99(17):1267-1274. Epub 2013 Jun 25.
3. Erglis A, Narbute I, Juhnevica D, Kumsars I, Jegere S. Lessons for the treatment of bifurcation lesions: from nowadays to the future. Intervent Cardiol. 2011;3:55-65.
4. Behan MW, Holm NR, Curzen NP, et al. Simple or complex stenting for bifurcation coronary lesions: a patient-level pooled-analysis of the nordic bifurcation study and the British Bifurcation Coronary Study. Circ Cardiovasc Interv. 2011;4(1):57-64. Epub 2011 Jan 4.
5. Kandzari DE. Drug-eluting stent thrombosis: it’s never too late. Nature clinical practice. Cardiovasc Med. 2006;3(12):638-639.
6. Udipi K, Chen M, Cheng P, et al. Development of a novel biocompatible polymer system for extended drug release in a next-generation drug-eluting stent. J Biomed Mater Res A. 2008;85(4):1064-1071.
7. Ferenc M, Kornowski R, Belardi J, et al. Three-year outcomes of percutaneous coronary intervention with new-generation zotarolimus-eluting stents for de novo coronary bifurcation lesions. J Invasive Cardiol. 2014;26(12):630-638.
8. Pillai AA, Jayaraman B. Dedicated bifurcation stents. Indian Heart J. 2012;64(2):187-195. Epub 2012 Apr 28.

__________________________________________

From the Department of Cardiovascular Medicine, Heart & Vascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Address for correspondence: Samin Sharma, MD, Director, Clinical & Interventional Cardiology, Zena & Michael A. Wiener Professor of Medicine, Mount Sinai Medical Center, 1 Gustave L Levy Place, New York, NY 10029. Email: samin.sharma@mountsinai.org