Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates - ZEUS

Mar 17, 2016
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Medtronic
Date Published:
03/07/2016
Date Updated:
03/17/2016
Original Posted Date:
02/23/2015
References

Description:

The goal of the trial was to compare the safety and efficacy of a shorter duration of dual antiplatelet therapy (DAPT) with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who were deemed uncertain DES candidates due to bleeding, thrombotic, or restenosis risk.

Contribution to the Literature: This study suggests that zotarolimus-eluting stents (ZES) may be preferable to BMS with shorter durations of DAPT in patients with unclear ability to take prolonged durations of DAPT.

Study Design

Patients were randomized in a 1:1 fashion to either Endeavor ZES (n = 802) or available thin strut BMS (n = 804).

Duration of antiplatelet therapy was prespecified based on the inclusion criteria. Patients at high bleeding risk received DAPT for 30 days. Patients at high risk of thrombosis had a prespecified tailored duration of therapy on the basis of the specific condition conferring the higher risk of thrombosis. This included a single antiplatelet regimen for patients intolerant to aspirin or available P2Y12 inhibitors, a 30-day regimen in stable patients, or 6-12 months in unstable patients, in the group at low risk of restenosis. Median duration of DAPT was 32 days (range 30-180 days).

Patient Population:

  • Total number of enrollees: 1,606
  • Duration of follow-up: 12 months
  • Mean patient age: 74 years
  • Percentage female: 30%
  • Percentage diabetics: 26%

Inclusion criteria:

  • Age 18 years or older
  • Uncertain DES recipient. This included:

High bleeding risk:

  • Clinical indication for treatment with oral anticoagulants
  • Recent bleeding episode(s) requiring medical attention
  • Previous bleeding episode(s) requiring hospitalization if the bleeding diathesis has not been completely resolved (that is, surgical removal of the bleeding source)
  • Age >80 years
  • Systemic conditions associated with increased bleeding risk (e.g., hematological disorders or any known coagulopathy-determining bleeding diathesis, including history of or current thrombocytopenia, defined as platelet count <100,000/mm3)
  • Known anemia (hemoglobin <10 g/dl)
  • Need for chronic treatment with steroids or nonsteroidal anti-inflammatory drugs

High thrombotic criteria:

  • Allergy/intolerance to aspirin
  • Allergy/intolerance to available P2Y12 inhibitors
  • Planned surgery (other than skin) within 12 months of percutaneous coronary intervention (PCI)
  • Patient with cancers (other than skin) and life expectancy >1 year
  • Patients with systemic conditions associated with thrombosis diathesis (e.g., hematologic disorders and any known systemic conditions determining a prothrombotic state)

Low restenosis risk:

  • No planned stent <3.0 mm diameter was intended to be implanted, irrespective of lesion length, apart from left main coronary artery or saphenous graft intervention

Other salient features/characteristics:

  • Previous PCI (19%)
  • Indication for PCI: stable angina (37%), non–ST-segment elevation myocardial infarction (NSTEMI) (27%), STEMI (19%)
  • Two-vessel disease: 34%, three-vessel disease: 25%
  • Reason for enrollment: high bleeding risk (51%), high thrombosis risk (18%)

Exclusion criteria:

  • Patients in whom, at the discretion of the treating physician, there was not clinical equipoise between BMS and DES (i.e., patients with diffuse three-vessel disease or complex bifurcation disease with planned bifurcation stenting or with Syntax score >33)
  • Pregnancy

Principal Findings:

The primary outcome, major adverse cardiac events (MACE) at 12 months (all-cause mortality, myocardial infarction [MI], target vessel revascularization) was lower in the ZES group (17.5%) compared with the BMS group (22.1%); p = 0.011.

Secondary outcomes:

  • All-cause mortality: 11.1% vs. 11.4%, p = 0.83
  • Cardiovascular death: 7.6% vs. 8.3%, p = 0.65
  • MI: 2.9% vs. 8.1%, p < 0.001
  • Target lesion revascularization: 5.2% vs. 10.4%, p < 0.001
  • Definite stent thrombosis: 1.0% vs. 2.2%, p = 0.05
  • TIMI major/minor bleeding: 1.7% vs. 2.1%, p = 0.72

Results were sustained in patients with high bleeding risk alone, who had higher MACE rates overall. BARC bleeding was nearly twofold higher in this cohort, but not different between the two arms.

Interpretation:

Among patients with uncertain ability to use DES with longer duration DAPT (median duration ~1 month) due to high bleeding, high thrombotic or low restenosis risk, ZES was superior to BMS for clinical outcomes, including MI, stent thrombosis, and target lesion revascularization; bleeding risk was similar.

These data provide further evidence that shorter durations of DAPT may be feasible with DES in select patient populations, especially where the temptation has been to use BMS to minimize DAPT duration. It is unclear if this benefit is specific to Endeavor ZES alone, or to EES and Resolute ZES as well, since the elution kinetics and stent designs are different.

References:

Ariotti S, Adamo M, Costa F, et al. Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention? A Pre-Specified Analysis From the ZEUS Trial. JACC Cardiovasc Interv 2016;9:426-436.

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;65:805-15.

Keywords: Drug-Eluting Stents, Sirolimus, Angina, Stable, Anticoagulants, Myocardial Infarction, Neoplasms, Percutaneous Coronary Intervention, Stents, Thrombosis, Thrombocytopenia


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