ZES Plus Tailored Course of Dual Therapy Reduces Adverse Events in Unlikely DES Candidates

WASHINGTON, DC—In patients not previously thought to be candidates for drug-eluting stents (DES), implantation with a zotarolimus-eluting stent (ZES) followed by an individualized course of dual antiplatelet therapy is associated with a lower risk of adverse events at 1 year compared with a bare-metal stent (BMS), according to results presented March 31, 2014, at the American College of Cardiology/i2 Scientific Session.

For the ZEUS (The Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates) trial, Marco Valgimigli, MD, PhD, of Erasmus Medical Center (Rotterdam, the Netherlands), and colleagues enrolled 1,606 patients at either high bleeding risk, high thrombotic risk, or low restenosis risk at 20 sites in Italy, Switzerland, Portugal, and Hungary from June 2011 to September 2012. Patients were randomized to implantation with either the Endeavor ZES (n = 802; Medtronic Vascular, Santa Rosa, CA) or a BMS (n = 804).

Dual antiplatelet therapy was designed according to the patient clinical risk profile irrespective of stent assignment:

  • High bleeding risk (52%): 30 days
  • High thrombotic risk (17%): none if aspirin/P2Y12 intolerant; up to surgery if planned; at least 6 months otherwise
  • Low restenosis risk (31%): 30 days for stable CAD; at least 6 months for ACS

While 4.6% of the overall population never received dual antiplatelet therapy, 43.6% and 62.5% discontinued at 1 and 2 months, respectively. More than one-third (37.5%) continued therapy beyond 2 months and about one-quarter (24.7%) remained on dual antiplatelet therapy beyond 6 months.

At 1 year, MACE was lower for those implanted with a ZES compared with a BMS, driven by reductions in TVR, MI, and definite/probable stent thrombosis (table 1).

Table 1. Outcomes at 1 Year

 

 

ZES
(n = 802)

BMS
(n = 804)

HR (95% CI)

P Value

MACE

17.5%

22.1%

0.76 (0.61-0.95)

0.011

TVR

5.9%

10.7%

0.53 (0.37-0.75)

< 0.001

MI

2.9%

8.1%

0.35 (0.22-0.56)

< 0.001

Definite/Probable Stent Thrombosis

2.0%

4.1%

0.48 (0.27-0.88)

0.019


In a post hoc analysis, the higher rates of type 1 (spontaneous) and type 4b (stent thrombosis-related) MI in the BMS arm drove ZES superiority. There were no differences in any bleeding events between treatment groups, and the benefit of ZES over BMS remained consistent across all prespecified subgroups.

“Our study suggests that Endeavor ZES may become the new gold standard coronary device in patients who cannot or refuse to tolerate long-term dual antiplatelet therapy,” Dr. Valgimigli concluded.

‘Unique Patient Subset with Clear Clinical Need’

Session comoderator Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), congratulated the researchers on “completing a randomized trial in a unique patient subset with a clear clinical need to improve patient outcomes.”

David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), agreed saying, “I think this is a welcome study in a patient population that vexes a lot us; both interventional and noninterventional cardiologists, and cardiologists and general practitioners alike. It also represents a reason in part why bare-metal stent utilization is still about 20% in the United States.”

He questioned the rates of stent thrombosis within the first year, as it is “interestingly higher with Endeavor” than other newer-generation DES. But Dr. Valgimigli countered that “the number of stent thromboses should not be cross-compared with other studies simply because no other study has so far randomized such a unique patient population.”

Study inclusion criteria included cancer and age higher than 80 years, Dr. Valgimigli explained. So “the question is whether in such a high-risk patient population with so many comorbidities, it makes sense to think about using BMS over DES at this time,” he said. “The outcome of our investigation is quite surprising. The MACE effect was largely driven by MI difference more than TVR itself. [This] probably suggests that DES, at least with some specific stents, should be considered in some of this patient population.”

Commenting specifically on the stent thrombosis issue, he said that what drove the difference between the treatment groups were events that occurred from 30 days to 1 year. “The vast majority of this type of stent thrombosis [reflects] late loss and therefore the results that you see here are not surprising. In these patients, you would never implant a bare-metal stent if you want to implant another DES,” he said.

Further Study Needed Regarding Stent Thrombosis

Panelist William W. O’Neill, MD, of Henry Ford Health System (Detroit, MI), questioned the risk of stent thrombosis in patients about to undergo surgery, claiming that “that’s a really tough problem for us.”

Dr. Valgimigli reported that a planned surgery was among the top inclusion criteria for patients in the high thrombotic risk group. “We ended up with almost 200 patients being randomized for that reason,” he said. “What we have seen is that there is no excess in stent thrombosis.”

Panelist Dean Kereiakes, MD, of The Christ Hospital (Cincinnati, OH), commented that even though newer generation DES have lower rates of stent thrombosis than BMS, all of the trials studying Endeavor have consistently shown a higher rate of stent thrombosis through 1 year. “If you do a meta-analysis, it’s highly significant,” he said. “I’m just not sure that this is a great strategy to adopt at this point—shorter duration dual antiplatelet therapy with this platform.”

While he agreed with this point, Dr. Valgimigli said, “I’m not sure either that it is a great strategy, but it is the only strategy that has been tested apart from BMS in this specific patient population. Whether other types of DES will be able to produce this benefit, it’s worth investigating.”

Study Details

Mean patient age was 74 years and almost one-third were women. Approximately one-quarter had diabetes, prior MI, or prior revascularization.

Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 


 

Source:Valgimigli M. Bare metal vs. zotarolimus-eluting stent in uncertain drug-eluting stent candidates: a randomized controlled trial (ZEUS). Presented at: American College of Cardiology/i2 Scientific Session; March 31, 2014; Washington, DC.

 

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Disclosures
  • ZEUS was funded by an unrestricted research grant from Medtronic.
  • Dr. Valgimigli reports receiving research grant funds from Medtronic and serving on the speaker’s bureau for Abbott, Astra Zeneca, CID Vascular, Iroko, Terumo, and The Medicines Company.

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