Battle of stents: New-gen wins, but no added advantage with biodegradable polymers
New-generation drug-eluting stents (DES) are superior to early-generation stents in reducing cardiovascular (CV) events and mortality out to 10 years, but there are no significant differences between new-generation stents based on biodegradable polymer and those with permanent polymer, according to the ISAR-TEST* 4 study presented at AHA 2018.
“This study once again refutes the age-old notion that improvement in stent design should not impact death or myocardial infarction [MI],” stated invited discussant Dr Sripal Bangalore of New York University School of Medicine in New York City, New York, US.
“This leads to the first take-home message [from the study]: Improvements in stent design can have meaningful impact on hard outcomes including death and/or MI. This has clinical implications for interpretation of trials that used older-generation DES/BMS**,” he added.
New-gen trumps early-gen DES
The long-term outcome analysis followed 2,603 patients with coronary artery disease who were randomized 2:1:1 to receive treatment with the new-generation Yukon Choice PC biodegradable polymer-based DES (BP-DES) or the Xience permanent polymer-based DES (PP-DES), or the first-generation Cypher PP-DES in ISAR-TEST 4. [AHA 2018, abstract LBS.06_18630; Circulation 2018;doi:10.1161/CIRCULATIONAHA.118.038065]
Over a median follow-up of 10.6 years, the primary endpoint of major adverse cardiac event (MACE) comprising a composite of MI, death, or target revascularization was significantly lower in both the new-generation BP- and PP-DES treatment arms (hazard ratio [HR], 0.82 and 0.79, respectively) compared with the group using the first-generation PP-DES. The incidence was 47.7 percent, 46.6 percent, and 54.9 percent, respectively for the three groups (p=0.003).
Furthermore, the finding remained consistent across subgroups prespecified by age, sex, and diabetes mellitus status.
Long-term mortality rate was also significantly lower with both the new-generation BP- and PP-DES than the first-generation DES (HR, 0.82 and 0.78, respectively), with significant difference overall (31.8 percent vs 30.3 percent vs 37.2 percent; p=0.02).
“The favourable outcome after new-generation DES is driven by increasing event rates over time in patients treated with early-generation DES,” said lead author Dr Sebastian Kufner from ISAResearch Centre in Munich, Germany. Both of the new-generation DES showed numerically fewer rates of MI, cardiac deaths, and target lesion revascularization compared with the early-generation DES.
The rates of definite stent thrombosis were also less common with both the new-generation DES than the early-generation DES, with significant difference among groups (1.1 percent vs 0.8 percent vs 2.4 percent; p=0.03); although the rates of combined definite/probable stent thrombosis were comparable among the three stents (1.8 percent vs 2.5 percent vs 3.7 percent; p=0.09).
“Early-generation DES technology showed an excess of adverse events attributable to very late stent thrombosis that continues to accrue at a constant rate after stent implantation,” Kufner pointed out. “Sustained accrual of events with early-generation DES means that intensified secondary prevention and surveillance of patients treated with these devices are warranted.”
Is biodegradable polymer the answer?
However, there were no significant differences between the new-generation BP- and PP-DES for all the clinical outcomes above.
“The absence of significant differences between BP-based sirolimus-eluting stents and PP-based everolimus-eluting stents over a 10-year time horizon means that meaningful clinical differences between the devices are unlikely to exist,” Kufner believed.
“[This leads to] the second take-home message that the late clinical benefit of BP-DES over second-generation PP-DES remains elusive … As shown in this trial and in other analyses, the BP-DES are at best noninferior to current generation PP-DES,” said Bangalore. “This begs the question as to whether paying a higher price for BP-DES (in certain healthcare systems) is justifiable.”
Noting that MACE rates continue to increase beyond 1 year (at about 3.3 percent/year) even with new-generation DES, he suggested that "continued progress in stent or scaffold technology, perhaps beyond the focus on polymer is warranted.”