Polymer-free less effective than polymer-based stent for PCI?
A polymer-free, thicker-strut, biolimus A9-eluting stent (BES) was not noninferior to a biodegradable-polymer, ultrathin-strut, sirolimus-eluting stent (SES) in unselected patients requiring percutaneous coronary intervention (PCI), the SORT OUT* IX trial has shown.
“The BES BioFreedom did not meet the criteria for noninferiority for major adverse cardiovascular events (MACE) at 12 months compared with the SES Orsiro in an all-comers population,” said the researchers.
“In our opinion, [the findings suggest that] the polymer-free BES [is] less efficacious than a conventional polymer-based drug-eluting stents (DES),” commented editorialists Professor Robert Byrne and Dr Róisín Colleran from the Mater Private Hospital in Dublin, Ireland. “[T]he comparator device … represents a high benchmark for comparison, potentially contributing to the efficacy gap observed.” [Circulation 2020;141:2064-2066]
The study comprised 3,151 patients (mean age 66 years) with 3,951 atherosclerotic coronary artery lesions. Participants were randomized 1:1 to receive either a BES or SES to manage the lesions. [Circulation 2020;141:2052-2063]
At 1 year, the rates of the composite endpoint MACE were similar between the BES and the SES arms (5.0 percent vs 3.7 percent; pnoninferiority=0.14). “[Although these reflect] low MACE rates in both stent groups … noninferiority of the BES [to SES] could not be demonstrated,” said the researchers.
There were also similar rates of all-cause mortality (2.0 percent vs 2.7 percent; p=0.16), cardiac death (1.0 percent vs 1.8 percent; p=0.05), and MI (2.4 percent vs 2.5 percent; p=0.73).
Rates of definite stent thrombosis were also similar between the two arms (0.7 percent for both; p=0.99). This finding aligns with those observed in other DES all-comer trials, [Lancet 2016;388:2607-2617; Lancet 2018;392:1235-1245] and was lower than the rates seen in another trial comparing a BES with a bare-metal stent. [N Engl J Med 2015;373:2038-2047]
The impact of TLR
“Failure to meet the noninferiority criteria was caused mainly by [the] higher rate of target lesion revascularization (TLR) in patients treated with the polymer-free BES,” the editorialists pointed out. TLR incidence was nearly threefold higher with BES vs SES (3.5 percent vs 1.3 percent; p=0.0001).
“The TLR curves started to diverge after 4 months and continued to do so throughout the study … The difference in TLR was driven by in-stent restenosis, where the mechanism probably is lesser efficacy on the inhibition of neo-intimal hyperplasia,” explained the researchers. They also attributed the high TLR rate with BES to strut thickness and rapid drug release.
The editorialists concurred, stating, “mechanistically, these design features provide a rationale for the differences in efficacy between the polymer-free BES and the comparator device.” The BES used in the study has faster drug release than other polymer-free devices, and is thicker than a majority of newer-generation DESs. [JACC Cardiovasc Interv 2016;9:51-64; Circulation 2001;103:2816-2821]
“DES efficacy is closely correlated with the release kinetics of the active drug in the first 30 days, especially in the first 10 days … The results provide further evidence that control of drug-release kinetics is critical to the clinical anti-restenotic efficacy of DES,” noted Byrne and Colleran. “[Strut thickness] is also of relevance because [it] is a known risk factor for in-stent restenosis.”
“[Nonetheless, the findings] are highly relevant for clinical practice,” said Byrne and Colleran. The performance and safety of the stents shall be evaluated annually up to 5 years following stent implantation.