Two zotarolimus-eluting stent generations: a meta-analysis of 12 randomised trials versus other limus-eluting stents and an adjusted indirect comparison

Objective To evaluate efficacy and safety of two zotarolimus-eluting stent generations versus other limus-eluting stents (LES), and to compare Resolute zotarolimus-eluting stents (R-ZES) with Endeavor zotarolimus-eluting stents (E-ZES). Background The performance of zotarolimus-eluting stents versus other LES, and the possible improvements of R-ZES versus E-ZES still remain to be defined. Methods We undertook a meta-analysis of trials in which patients were randomly assigned to percutaneous coronary interventions (PCI) with R-ZES versus LES, or with E-ZES versus LES, as well as an indirect comparison of R-ZES versus E-ZES, with LES as common comparator. The primary efficacy endpoint was ischaemia-driven target vessel revascularisation (ID-TVR); the primary safety endpoints were myocardial infarction (MI), cardiac death and cumulative definite/probable stent thrombosis (ST). Results Overall, 13'709 patients were assigned to PCI with R-ZES versus LES (n=7185) or with E-ZES versus LES (n=6524). The risk of ID-TVR (OR (95% CI)=1.06 (0.90 to 1.25), p=0.47), MI (1.00 (0.81 to 1.25), p=0.97), cardiac death (0.99 (0.69 to 1.42), p=0.96) and ST (1.18 (0.68 to 2.03), p=0.56) did not differ between R-ZES and LES. Patients receiving E-ZES were more likely to undergo ID-TVR as compared with those receiving LES (1.95 (1.40 to 2.73), p<0.0001). The risk of MI (0.91 (0.54 to 1.54), p=0.73), cardiac death (1.02 (0.54 to 1.91), p=0.96) and ST (1.10 (0.50 to 2.44), p=0.81) was similar between E-ZES and LES. At indirect comparison, PCI with R-ZES versus E-ZES reduced the risk of ID-TVR (0.54 (0.37 to 0.78), p=0.001), without increasing MI (1.09 (0.62 to 1.93), p=0.74), cardiac death (0.97 (0.46 to 2.00), p=0.93) and ST (1.07 (0.40 to 2.80), p=0.88). Conclusions The antirestenotic efficacy of Resolute zotarolimus-eluting stents is superior to Endeavor zotarolimus-eluting stents and similar to other limus-eluting stents. Endeavor zotarolimus-eluting stents increase the risk of reinterventions as compared with other limus-eluting stents. First and second-generation zotarolimus-eluting stents have similar thrombogenicity compared with other limus-eluting stents.