Safety of the COMBO® Plus Dual Therapy Stent

Very Low Stent Thrombosis Rates Reported In Multiple Studies Out to 5-years

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Alain Khair +31332541150

November 6, 2020: An assessment of the safety and clinical performance of the COMBO Plus Dual Therapy Drug-Eluting Stent (“COMBO stent”) shows consistently good safety, as reflected in the very low occurrence definite/probable stent thrombosis (ST) now out to 5-years follow up.  The COMBO stent has been designed with a proprietary EPC capture technology for rapid neointimal healing.  Delayed healing and incompletely covered stent struts have been associated with the occurrence of late stent thrombosis, an extremely serious clinical event associated with high mortality.  The safety of the COMBO stent has been demonstrated in multiple controlled clinical studies with definite/probable ST < 1% in a broad spectrum of patient populations as described for the following studies:

HARMONEE – No ST at 1-year follow up (n=287)[1]
The HARMONEE trial was a regulatory approval trial conducted in Japan and the US where there was 1-year angiographic follow-up in all 287 patients receiving the COMBO stent.  The diverse Asian and North American patient population in HARMONEE included 16% of the subjects presenting with an acute coronary syndrome (ACS) and 31% of the treated lesions were ACC/AHA type B2/C lesions.  At 1-year there were no incidents of stent thrombosis (ST) in the COMBO cohort.  The COMBO stent demonstrated significantly superior healthy tissue stent strut coverage as determined by optical coherence tomography (OCT) imaging at 12 months compared to the XIENCE stent comparator; strut coverage at 91.3% versus 74.8% respectively (p<0.001).

REDUCE – 0.8% ST at 1-year follow up (n=1,460)[2]
The physician-initiated REDUCE trial was conducted at 36 centers in Europe and Asia Pacific in an all ACS patient population of 1,460 subjects where a 3-month duration of dual anti-platelet therapy (DAPT) was compared to the guideline mandated 12-month DAPT in 1,460 patients receiving the COMBO stent.  Almost half of the study patients presented with acute ST-segment elevated myocardial infarction (STEMI).  In this highly pro-thrombotic ACS patient set, the guideline treated cohort showed very low ST and the overall study cohort exhibited a 0.8% definite/probable ST rate at 1-year.

MASCOT – 0.9% ST at 1-year follow up (n=2,614)[3]
The MASCOT post-market “real-world” registry was conducted at 60 centers in Europe, the Middle East, Asia Pacific, and South America.  A total of 2,614 patients receiving the COMBO stent were enrolled in the registry, in a complex patient population which included 56% of subjects presenting with ACS and 58% of the lesions treated were ACC/AHA type B2/C.  A 0.9% definite/probable ST rate at 1-year was reported in this diverse and complex patient cohort.

REMEDEE Registry – 0.6% ST at 1-year and 0.9% at 5-years (n=1,000)[4]
The physician-initiated REMEDEE Registry was designed as a “all-comers” registry conducted by nine European centers and enrolling 1,000 patients receiving the COMBO stent.  The diverse, complex patient population in the study included 50% of the patients presenting with ACS and 58% of the lesions treated were ACC/AHA type B2/C lesions.  The study reported a 0.6% definite/probable ST rate at 1-year and a 0.9% definite/probable ST rate at 5-years.  In the first year, all of the ST cases were reported in the first nine days after the index procedure.  In the late follow up, there were no ST cases reported between years three and five, indicative of the long-term stability of the stent healing.

“When you compare the healing capabilities of COMBO stent to other drug eluting stents, I believe healing with the EPC capture  technology clearly offers some superior aspects, it’s a clear differentiation to other stents”.

Prof Michael Haude

The safety profile of the COMBO stent observed in the above-mention clinical studies have been used to support the CE-mark approved labeling claims informing physician users with a unique option of flexibility in considering a shorter dual antiplatelet regimen for those patients for whom the standard DAPT duration is contraindicated or other medical conditions may require DAPT interruption or discontinuation.  These claims regarding DAPT flexibility under patient unique circumstances where the guideline recommendations cannot be adhered to are consistent with the recognized need for individualized treatment with PCI patients.

About COMBO

There are multiple design features that make COMBO a unique and effective option for treating coronary stenosis. Following implantation, an exclusive biological coating on the outer surface of the COMBO immediately captures circulating endothelial progenitor cells from the blood and initiates the formation of an endothelial layer. This accelerated healing process, leads to earlier return of endothelial functionality. Together with the biological layer, a directional coating of bioabsorbable polymer elutes sirolimus to inhibit neointimal hyperplasia.  This unique design combines accelerated healing with the effective control of restenosis.

About OrbusNeich

OrbusNeich is a global pioneer in the provision of life-changing vascular solutions and offers an extensive portfolio of products that set industry benchmarks in vascular intervention.  Current products include the world’s first dual therapy stents, the COMBO® Plus and COMBO® Dual Therapy Stents, together with coronary stents, speciality balloons, balloons, and microcatheters marketed under the names of Azule®, Scoreflex®, Scoreflex® NC, Sapphire®, Sapphire® II, Sapphire® II PRO, Sapphire® 3, Sapphire® NC, Sapphire® NC Plus, Sapphire® II NC, Sapphire® NC 24, Teleport® and Teleport® Control as well as products to treat peripheral artery disease: the Jade® and Scoreflex® PTA balloons. 

OrbusNeich is headquartered in Hong Kong and has operations in Shenzhen, China; Fort Lauderdale, Florida, USA; Hoevelaken, The Netherlands; Zuchwil, Switzerland; Germany; Spain; Tokyo, Japan; Singapore; Kuala Lumpur Malaysia.  OrbusNeich supplies medical devices to physicians in more than 60 countries. For more information, visit www.OrbusNeich.com.


[1] Saito S et al.European Heart J (2018) 39:2460-2468

[2] G. de Luca et al, EuroIntervention, August 2019

[3] A. Colombo et. al, International Journal of Cardiology, May 2019

[4] L.S. Kerkmeijer et al. Catheterization & Cardiovascular Interventions, October 2020  


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