ZEUS Study of Uncertain DES Candidates Presented

March 31, 2014—Medtronic, Inc. (Minneapolis, MN) announced that findings from the ZEUS study of the company’s Endeavor Sprint zotarolimus-eluting stent (ZES) in uncertain drug-eluting stent (DES) candidates were presented by ZEUS lead investigator Marco Valgimigli, MD, at ACC.14, the 63^rd annual scientific session of the American College of Cardiology, held in Washington, DC.

Some patients were previously thought to be uncertain candidates for DES due to their heightened risk of bleeding or blood clots. This study demonstrated that the use of DES is associated with a lower risk of major cardiovascular events at 1 year compared to bare-metal stents (BMS) when followed by an individualized course of blood-thinning medication among these uncertain candidates.

The ZEUS investigators advised that these positive study findings for patients receiving a shorter course of blood thinners than is currently recommended may call into question existing guidelines for a more prolonged antiplatelet therapy after DES placement, which points to the need for a more personalized approach. 

According to Medtronic, the ZEUS multinational, single-blinded trial was composed of 1,606 patients who were randomly assigned to receive a ZES or a BMS. The purpose of the study was to assess whether implantation of the DES followed by an individualized course of dual-antiplatelet therapy (DAPT, a combination of aspirin and an antiplatelet drug) would decrease the incidence of 12-month major adverse cardiovascular events (MACE) compared to implantation with a BMS in patients classified as uncertain candidates for DES.

The ZEUS investigators found that at 1 year, a significantly higher number of patients in the BMS group experienced MACE, including all-cause death, nonfatal heart attacks, or any procedures to reopen the artery.

As summarized by Medtronic, 140 patients (17.5%) treated with DES had a MACE in the first year compared with 178 patients (22.1%) implanted with the BMS. Patients with the DES compared to BMS patients also had lower rates of heart attacks (2.9% vs 8.1%), procedures to reopen the artery (5.9% vs 10.7%), and blood clots around the stent (2% vs 4.1%). The rate of bleeding did not differ between groups.

The ZEUS study enrolled 1,606 patients undergoing percutaneous coronary intervention with stent implantation at 20 sites in Italy, Switzerland, Portugal, and Hungary. The patients were randomly assigned to receive BMS or DES. All patients were adults who met any one of the three criteria to be uncertain candidates for DES: a high risk of blood clots, a high risk of bleeding, or a low risk of restenosis. Patients at a low risk of restenosis were included because the risk of blood clots associated with DES, along with the assumed risk of bleeding from the prolonged course of blood thinners taken afterward, may outweigh the benefits of this type of stent for these patients.

Medtronic noted that the majority of patients (95.4%) took some course of DAPT after stent placement: 96.7% were treated with aspirin and clopidogrel, and the remaining 3.3% were treated with aspirin and either prasugrel or ticagrelor. Duration of therapy was dictated by patients’ individual risk factors and spanned from no treatment to 6 to 12 months with a median of 32 days. Patients who were not eligible for DAPT were treated with either aspirin or an antiplatelet alone. This protocol represents a departure from current guidelines that recommend the use of DAPT for 6 to 12 months after the placement of a DES.

In Medtronic’s press release, Dr. Valgimigli, who is a cardiologist and associate professor at Erasmus University Medical Center in Rotterdam, the Netherlands, commented, “Given the assumed risks, we were surprised by the lower rate of heart attack and blood clots among our DES patients. For the first time, we have handled a DES as we would a BMS in terms of the duration and intensity of antiplatelet therapy and have still shown the superior safety and efficacy of the DES.”

Medtronic noted that the investigators cautioned that the results of this study pertain to the ZES and may not apply to other types of DES. Dr. Valgimigli advised that additional research is needed to determine whether the personalized DAPT tested in this study can be safely implemented in patients using other types of DES, and suggested that a longer follow-up study be conducted to confirm results of this study over time.