Endeavour zotarolimus-eluting stent reduces stent thrombosis and improves clinical outcomes compared with cypher sirolimus-eluting stent: 4-year results of the PROTECT randomized trial
Selected in European Heart Journal by G.G. Toth
Wijns W, Steg PG, Mauri L, Kurowski V, Parikh K, Gao R, Bode C, Greenwood JP, Lipsic E, Alamgir F, Rademaker-Havinga T, Boersma E, Radke P, van Leeuwen F, Camenzind E
Eur Heart J. 2014 Oct 21;35(40):2812-20
LinkAccess the Abstract
The Patient Related OuTcomes with Endeavor versus Cypher Stenting Trial (PROTECT) was designed to compare long-term clinical safety between a zotarolimus-eluting stent platform (EndeavorTM; E-ZES) and a sirolimus-eluting stent platform (Cypher TM;C-SES). Note, that the two stents have different metal structures, different polymers and different drugs.
Between May 2007 and December 2008, 8709 patients were randomized 1:1 to receive either E-ZES (4357 patients) or C-SES (4352 patients) but otherwise treated according to clinical practice. The primary endpoint was definite or probable stent thrombosis at 3 years. The main secondary outcomes included combinations of death and myocardial infarction (MI) at 3 years. Key safety and efficacy metrics were collected up to 4 years, as presented in the present manuscript.
Besides a majority of patients with stable coronary artery disease, the indication for angioplasty at the time of enrollment was MI (ST or non-ST-segment elevation) in 26% of subjects, and unstable angina in 19%.
As published earlier, with similar use of DAPT between groups at all follow-up intervals the primary outcome of definite or probable stent thrombosis, as well as the clinical outcome combining death and MI did not show significant differences at 3 years.
- The primary outcome of definite or probable stent thrombosis at 4 years occurred in 1.6% of E-ZES vs. 2.6% of C-SES patients [HR 0.63 (95% CI 0.46– 0.85), p = 0.003]. This difference was driven by the higher rates of very late (>1 year) definite or probable stent thrombosis.
- The incidence of death or large non-fatal MI at 4 years were lower with E-ZES [6.7 vs. 8.0%, HR 0.84 (95% CI 0.71–0.98), p = 0.024], as were rates of death and any MI [9.2 vs. 10.8%, HR 0.85 (95% CI 0.74–0.97), p = 0.017]. These differences in main secondary endpoints were driven by differences in events beyond 1 year.
- Clinically driven target lesion revascularization was significantly reduced with C-SES (4.5 vs. 5.9%, p = 0.002) while clinically driven target vessel revascularization was not (8.6% with C-SES vs. 9.0% with E-ZES, p = 0.37).
PROTECT study resulted in a really low rate of definite or probable stent thrombosis after 4 years. But still, there is a statistically, as well as clinically important difference between outcomes of the two groups. Although this comparison might sound historical in the era of third generation drug-eluting stents, data underline that the choice of different stent platforms can be associated with significant differences in hard clinical endpoints such as stent thrombosis, large non-fatal MI or death.
Importantly, the differences in both the primary- and the secondary endpoints were driven by late events, occurring over 1 year follow-up. Accordingly, well-powered studies with sufficiently long term follow-up are of crucial importance to detect the potential benefits or risks associated to a given stent platform as compared to others.