Reviewer: Dr. Muammer Karakayalı

The name of the study: A Hybrid Approach Evaluating a DRug-Coated Balloon in Combination With a New-Generation Drug-Eluting Stent in the Treatment of De Novo Diffuse Coronary Artery Disease: The HYPER Pilot Study

Published Congress: EuroPCR 2022

Background: Contemporary DES are associated with a persistent risk of major cardiovascular events, due to instent thrombosis and restenosis. However, even with the next generation DES, concern for late adverse events remains due to a permanently rigid metallic cage. The use of drug-coated balloon (DCB) is a promising tool for the treatment of instent restenosis (ISR) and de novo coronary artery disease (CAD) involving segments of small reference vessel diameter (RVD).

Objectives: To assess feasibility, safety and efficacy of hybrid approach, consisting of a combination of modern drug-eluting stent (DES) and drug-eluting balloon (DCB), for treatment of de-novo diffuse coronary artery disease (CAD).

Methods: This is a prospective, non-randomized, observational, multicenter study intended to obtain data from 100 consecutive patients affected by de-novo diffuse CAD undergoing percutaneous coronary intervention with a hybrid approach, consisting of the combined use of DES and DCB in contiguous coronary segments. The “hybrid strategy” was defined as overlapping or slightly (2-3 mm) superimposing a new generation DES implanted in the larger RVD>2.75 mm, more proximal part of the vessel or in the main branch (MB) of a bifurcation, and DCB inflation for a contiguous small vessel disease (RVD ≥ 2.0 mm to <2.75 mm) located in the distal segment or at a side branch (SB) of a bifurcation. Procedural success was defined as both DES/DCB delivery and implantation to the “target” lesion site with <30% stenosis in the DCB treated segment and <10% stenosis in the DES-treated segment and distal TIMI 3 flow. The primary end-point of the study was a device oriented composite end-point (DOCE) of cardiac death, target vessel myocardial infarction (TV-MI) and ischemia-driven target lesion revascularization (ID-TLR) in the DES- and/or the DCB-treated segment within 12 months after the index procedure.

Inclusion Criteria;

1-Patients presenting with stable or unstable de novo CAD eligible for percutaneous coronary intervention (PCI) (according to the international  guidelines)  because  of  diffuse CAD involving target segments suitable for a hybrid approach,
2-Agreeing to sign Patient Informed Consent/Data Release Form.

Exclusion Criteria

1-Age <18 years,
2-Cardiogenic shock,
3-Pregnancy or breastfeeding,
4-Reference  vessel  diameter  (within  planned device  deployment  segment) >5.0  mm <2.0 mm,
5-Comorbidities with life expectancy <1 year,
6-Severe calcification or/tortuosity proximally or at the DCB target –segment,
7-Patients  with  known  allergies  or  absolute contraindications  to  aspirin,  clopidogrel  or ticagrelor.

Results: In-hospital outcomes were procedural success in 102 patients (96.2%), periprocedural MI in 10 patients (9.4%), current requiring stenting limiting dissection in 3 patients (2.9%), major bleeding (according to BARC classification) in 3 patients (2.8%). Of the 1-year outcomes, the device-focused composite endpoint was seen in 4 patients (3.7%); cardiac death; target vessel MI (except procedural MI) and thrombosis in the DCB or DES target segment were not seen in any of the patients.

Conclusion: The HYPER pilot study suggested that an hybrid approach combining the use of DES and restore DCB for the treatment of de novo diffuse CAD is:

1-Feasible and associated with a high rate of procedural success,
2-Low incidence of 1-year DOCE,
3-Long lesions associated with a numerically higher ID-TLR rate,
4-Larger and more robust data from RCTs are needed to confirm our findings.

Interpretations: The risk is expected to be higher especially in the context of complex and diffuse coronary artery lesions (such as bifurcations and long lesions involving small vessels). Diffuse CAD is considered a challenging setting in interventional cardiology, since up to date evidence concerning the best treatment are not unequivocal. New treatment strategies are needed. A combination therapy of DCB and DES (defined as hybrid approach)  has the advantage to reduce the length of the permanent metallic cage, which in turn can be beneficial for lower restenosis rate. In the hybrid approach for diffuse disease, the sequential lesions should be treated separately with DES implanted for the proximal segment (or main branch) and DCB angioplasty for the distal lesion (or side branch).