ZEUS Published: ZES With Personalized DAPT Bests Bare-Metal Stent in ‘Uncertain’ DES Candidates

Patients at high risk of bleeding or thrombosis and/or low risk of restenosis who are considered uncertain candidates for DES have fewer major adverse events when treated with a novel zotarolimus-eluting stent (ZES) and an abbreviated course of antiplatelet therapy than with a BMS, according to a study published in the March 3, 2015, issue of the Journal of the American College of Cardiology.

The results were first presented in March 2014 at the American College of Cardiology/i2 Scientific Session in Washington, DC.

For the ZEUS (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 high bleeding risk (51.6%), high thrombotic risk (17.7%), or low restenosis risk (58.6%; some had more than 1 risk) at 20 European sites from June 2011 to September 2012. The median age was 74 years; approximately one-quarter of the population had a history of diabetes or previous MI, more than 40% had impaired kidney function, more than 50% had multivessel disease, and approximately 75% had at least 1 complex lesion.

Patients were randomized to receive either the hydrophilic polymer-based Endeavor ZES with fast drug release (n = 802; Medtronic) or a BMS (n = 804).

Overall, about two-thirds of patients in each group qualified for 30-day dual antiplatelet therapy (DAPT) or a single antiplatelet regimen. The median duration of DAPT—32 days—did not differ between groups (P = .69).

MI, TVR, Stent Thrombosis All Lower With ZES

At 1 year, the rate of MACE (death, MI, or TVR) was lower in the ZES vs the BMS group, driven by substantial reductions in TVR and MI. No differences were seen in all-cause and cardiovascular mortality or major bleeding. However, ZES patients had half the rate of definite or probable stent thrombosis as BMS patients.

Dr. Valgimigli and colleagues note that ZEUS comprised a unique patient population largely excluded from the trials that led to approval of ZES.

“Furthermore, the duration of antiplatelet therapy specified in the protocol was based not on the type of stent implanted (DES vs BMS) but on the patient’s perceived risk profile,” they write.

According to the authors, the reductions in MI and stent thrombosis in the ZES group were “unexpected.” They note that in post hoc analysis, spontaneous and stent thrombosis-related MI were reduced in the ZES arm, whereas other types of MI, including periprocedural events, did not differ between groups. Furthermore, in sensitivity analyses, the MACE benefit was consistent regardless of whether patients received the abbreviated 30-day DAPT regimen or a single agent.

Dr. Valgimigli and colleagues say these results “suggest, for the first time, that ZES implantation followed by a personalized duration of DAPT, including a 30-day course of DAPT, is a novel and attractive strategy to reduce rates of MACE without increasing the risk of bleeding.”

However, they caution that “further follow-up is needed to ascertain the long-term clinical implications of these findings, specifically the effect on cumulative bleeding endpoints of long-term DAPT duration in the BMS group and in the subgroup of patients (numerically almost 2-fold more than in the ZES group) who required reintervention for in-stent restenosis.”

They also point out that further research is needed to determine if the tailored DAPT regimen can be safely used with other types of DES.

Do BMS Still Serve a Purpose?

In an editorial accompanying the study, David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), says the ZEUS study “informs treatment decisions for patients underrepresented by evidence-based medicine and whose clinical picture cannot be painted with broad and common strokes.”

Importantly, Dr. Kandzari says, ZEUS “tested a very common dilemma related to stent selection, contested more generalized guideline recommendations, and offered a model for treatment decisions on the basis of individualized risk and/or benefit assessment rather than a ‘one-size- fits-all’ strategy.”

Additionally, he says the results “challenge whether there remains a clinical purpose for BMS.”

The European Society of Cardiology has already taken a stand on the abbreviated DAPT issue, he observes, by recommending less than 6 months of DAPT after DES for patients with bleeding risk who receive newer-generation DES.

Dr. Kandzari adds that nonrandomized data on newer DES suggest a low risk of ischemic events with DAPT durations as short as 1 month. However, randomized trials are needed to confirm whether this strategy is safe. The ongoing GLOBAL LEADERS study is testing this theory with use of a biodegradable-polymer DES.

Sources:
1. Valgimigli M, Patialiakas A, Thury A, et al. Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates. J Am Coll Cardiol. 2015;65:805-815.

2. Kandzari DE. Stent selection and antiplatelet therapy duration: one size does not fit all [editorial]. J Am Coll Cardiol. 2015;65:816-819.

Disclosures:

• The ZEUS trial was funded by an unrestricted research grant from Medtronic.
• Dr. Valgimigli reports receiving honoraria for lectures/advisory board and research grants from Eli Lilly, Iroko, Medtronic, and Merck; honoraria for advisory board and lectures from Abbott Vascular, Daiichi Sankyo, Eli Lilly, St. Jude, and The Medicines Company; and lecture fees from CID, Cordis, and Terumo.
• Dr. Kandzari reports receiving research/grant support from Abbott Vascular, Biotronik, Boston
• Scientific, Medinol, and Medtronic CardioVascular and consulting honoraria from Boston Scientific, Medtronic CardioVascular, and Micell Technologies.