The PROTECT (Patient Related Outcomes with Endeavor versus Cypher stenting trial) study, which was presented as a late-breaking trial at the annual meeting of the European Society of Cardiology (ESC, 25–29 August, Munich, Germany) and simultaneously published online in The Lancet, failed to fulfil its hypothesis that Medtronic’s Endeavor zotarolimus-eluting stent would be superior to Cordis’ Cypher sirolimus-eluting stent in terms of reducing the rate of definite or probable stent thrombosis.
Edoardo Camenzind, University of Geneva, Switzerland, and others reported in The Lancet that the drug, polymer, and stent characteristics of drug-eluting stents differ and that, potentially, these variations may affect the risk of stent thrombosis. They explained that the Endeavor zotarolimus-eluting stent is associated with a low rate of late stent thrombosis and has similar vascular healing responses to a bare metal stent. However, they added that randomised studies comparing Endeavor to other stents have not reviewed stent thrombosis or late outcomes. Camenzind et al wrote: “We aimed to see if the Endeavor zotarolimus-eluting stent was better than the Cypher sirolimus-eluting stent with respect to incidence of definite or probable stent thrombosis at three years after coronary stent implantation.”
Presenting the results of the PROTECT study at the ESC, study author William Wijns, Cardiovascular Center, OLV Hospital, Aalst, Belgium, said: “PROTECT included real-world patients with an indication for single or multiple coronary lesion percutaneous coronary intervention. They were randomised one to one to treatment with either Endeavor or Cypher.” He added that the primary endpoint was the composite of definite or probable stent thrombosis at three years and that the principle secondary endpoints were designed to “capture the sequelae of stent thrombosis, namely death or myocardial infarction.” Wijns commented: “I would like to stress that PROTECT is the largest trial comparing drug-eluting stents ever reported so far and also that PROTECT is the first randomised controlled trial that is adequately powered for comparing stent thrombosis rates between drug-eluting stents.” All patients received dual antiplatelet therapy (aspirin and clopidogrel [Plavix, Sanofi-Aventis and Bristol-Myers Squibb]) as per instructions for use or per guidelines recommendations (3–12 months) at the discretion of the physicians. Wijns said: “Importantly, there was no difference between groups in antiplatelet use at any time point.”
Of the 8,709 patients enrolled in the study, 4,357 received the Endeavor stent and 4,352 received the Cypher device. Wijns said: “The primary endpoint of definite or probable stent thrombosis at three years did not differ [significantly] between groups. Stent thrombosis was low, as expected, with Endeavor and was lower than expected with Cypher.
The hazard ratio was 0.81.” He added that after one month, definite or probable stent thrombosis was higher with Endeavor between 31 and 360 days but higher for Cypher between one year and three years. Additionally, in terms of the principle secondary endpoints, there were no significant differences between the two groups. Wijns said: “The need for repeat revascularisation, be it target lesion revascularisation or target vessel revascularisation and MACE [Major adverse cardiovascular events] were higher with Endeavor. However, overall, all event rates were low with both groups.”
According to Wijns, a pre-specified exploratory timed analysis indicated that a difference between groups could emerge over time. He said: “This was shown for definite or probably stent thrombosis and also for definite stent thrombosis, with a higher rate for the Cypher stent.”
Concluding, Wijns said: “PROTECT trial is the largest prospective randomised head-to-head comparison of drug-eluting stents and demonstrates the following: that there is no difference in definite or probable stent thrombosis rates between Endeavor and Cypher.” He added that the timed analysis, which suggested that a difference could emerge over time, emphasised the importance of continued follow-up. He said: “Large pragmatic trials such as PROTECT are essential to determine the differential outcomes between drug-eluting stents and to capture the impact of improved procedural and clinical practice on stent thrombosis rates over time.”
Discussing the results of PROTECT, Stephan Windecker (head of interventional cardiology, Swiss Cardiovascular Center Bern, Switzerland) said: “Although PROTECT failed to show a significant difference between stent types for the primary endpoint of definite or probable stent thrombosis, findings of secondary outcomes–namely definite and very late definite stenosis confirm previous concerns of delayed arterial healing with early generation stents [ie, Cypher].” He added that stent thrombosis was “no longer an issue” with newer generation drug-eluting stents and previous safety concerns had been resolved without compromising safety.