Patient Related OuTcomes with Endeavor versus Cypher stenting Trial - PROTECT (Endeavor vs. Cypher)

Description:

The goal of the trial was to evaluate percutaneous coronary intervention (PCI) with the Endeavor zotarolimus-eluting stent compared with the Cypher sirolimus-eluting stent among a broad selection of patients.

Hypothesis:

The Endeavor zotarolimus-eluting stent will be associated with a lower incidence of stent thrombosis.

Study Design

  • Randomized
  • Parallel
  • Stratified

Patient Populations:

  • Patients at least 18 years of age undergoing elective or emergent PCI of a native coronary artery

    Number of screened applicants: 8,791
    Number of enrollees: 8,709
    Duration of follow-up: 4 years
    Mean patient age: 62 years
    Percentage female: 23%
    Ejection fraction: 59%

Exclusions:

  • Implantation of a bare-metal stent in the last 12 months, or prior drug-eluting stent or brachytherapy

Primary Endpoints:

  • Definite or probable stent thrombosis

Secondary Endpoints:

  • Total death and large nonfatal myocardial infarction
  • Cardiac death and large nonfatal myocardial infarction
  • Definite stent thrombosis
  • Target lesion revascularization
  • Target vessel revascularization
  • Major adverse cardiac events
  • TIMI major bleeding

Drug/Procedures Used:

Patients undergoing elective or emergent PCI of a native coronary artery were randomized to the Endeavor zotarolimus-eluting stent (n = 4,357) versus the Cypher sirolimus-eluting stent (n = 4,352).

Concomitant Medications:

Post-PCI, aspirin was recommended indefinitely, and clopidogrel for 3-12 months (or longer) according to physician discretion.

Principal Findings:

Overall, 8,709 patients were enrolled. The mean age was 62 years, 23% were women, 27% had diabetes, procedure indication was acute coronary syndrome in 26%, mean left ventricular ejection fraction was 59%, ACC/AHA lesion class B2/C was present in 54% (slightly more complex lesions in the sirolimus group), mean reference vessel diameter was 3.0 mm (slightly smaller vessel diameter in the sirolimus group), and mean lesion length was 18 mm. Unfractionated heparin was used in 92%, and a glycoprotein IIb/IIIa inhibitor was used in 18%.

Dual antiplatelet therapy was used in 96% of patients at discharge: 88% at 1 year, 37% at 2 years, 30% at 3 years, and 27% at 4 years.

At 3 years, definite or probable stent thrombosis occurred in 1.4% of the zotarolimus-eluting stent group versus 1.8% of the sirolimus-eluting stent group (p = 0.22). There was no difference in stent thrombosis between groups within 30 days (0.7% vs. 0.6%); however, between 31 and 360 days, there were more events with the zotarolimus-eluting stent (0.4% vs. 0.1%) and between 361 and 1,080 days, there were fewer events with the zotarolimus-eluting stent (0.3% vs. 1.1%).

- Total death and large nonfatal myocardial infarction: 5.3% versus 6.0% (p = 0.16)
- Cardiac death and large nonfatal myocardial infarction: 3.7% versus 4.1% (p = 0.33)
- Definite stent thrombosis: 0.7% versus 1.2% (p = 0.03)
- Target lesion revascularization: 5.6% versus 3.5% (p < 0.0001)
- Target vessel revascularization: 8.2% versus 7.1% (p = 0.03)
- Major adverse cardiac events: 12.3% versus 10.8% (p = 0.02)
- Thrombolysis in Myocardial Infarction (TIMI) major bleeding: 1.8% versus 1.6% (p = 0.51)

At 4 years, definite or probable stent thrombosis occurred in 1.6% of the zotarolimus-eluting stent group versus 2.6% of the sirolimus-eluting stent group (p = 0.003). There was also a reduction in death or large myocardial infarction with zotarolimus-eluting stents, 6.7% versus sirolimus-eluting stents, 8.0% (p = 0.024).

Interpretation:

Among a broad group of patients undergoing PCI of a native coronary artery and mostly treated with dual antiplatelet therapy for 1 year, the Endeavor zotarolimus-eluting stent did not reduce 3-year stent thrombosis compared with the Cypher sirolimus-eluting stent. The zotarolimus-eluting stent was associated with slightly more stent thromboses between 31 and 360 days, and slightly fewer stent thromboses between 360 and 1,080 days. This likely reflects the hazard of very late stent thrombosis of first-generation drug-eluting stents during a time when most patients were only on mono antiplatelet therapy.

Efficacy was a secondary outcome in this trial; however, the sirolimus-eluting stent was associated with fewer target lesion revascularizations, target vessel revascularizations, and major adverse cardiac events.

The incidence of stent thrombosis was similar between the groups until approximately 2 years. From 2 to 4 years, the risk of stent thrombosis with zotarolimus-eluting stents appeared to plateau, while the risk continued to increase with sirolimus-eluting stents. These devices have largely been replaced with newer-generation stents; however, this study has relevance to patients already implanted with one of these stents.

References:

Wijns W, Steg PG, Mauri L, et al. Endeavor zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent: 4-year results of the PROTECT randomized trial. Eur Heart J 2014;Aug 8:[Epub ahead of print].

Presented by Dr. Laura Mauri at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2013), San Francisco, CA, October 28, 2013.

Camenzind E, Wijns W, Mauri L, et al., on behalf of the PROTECT Steering Committee and Investigators. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial. Lancet 2012;380:1396-405.

Presented by Dr. William Wijns at the European Society of Cardiology Congress, Munich, August 27, 2012.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Invasive Cardiovascular Angiography and Intervention, Anticoagulation Management and ACS, Interventions and ACS

Keywords: Acute Coronary Syndrome, Myocardial Infarction, Follow-Up Studies, Drug-Eluting Stents, Heparin, Sirolimus, Percutaneous Coronary Intervention, Stents, Thrombosis, Stroke Volume, Coronary Vessels, Diabetes Mellitus, Platelet Glycoprotein GPIIb-IIIa Complex


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