October 17, 2020
Svelte Medical Systems' Slender IDS DES Evaluated in OPTIMIZE Trial
October 17, 2020—The OPTIMIZE randomized trial evaluated a novel, low-profile drug-eluting stent (DES) facilitating transradial (TR) access and direct stenting (DS) in comparison to an existing DES. The device studied was the Slender IDS DES with integrated delivery system by Svelte Medical Systems, which funded the trial.
The trial's results did not establish noninferiority of the new stent based on the prespecified study statistical analysis plan, likely because the definition of the periprocedural target vessel myocardial infarction (TVMI) coupled with a large proportion of high-sensitive cardiac troponin assays used in the trial.
Lead investigator Dean J. Kereiakes, MD, presented the OPTIMIZE findings at TCT Connect, the 32nd annual Transcatheter Cardiovascular Therapeutics scientific symposium of the Cardiovascular Research Foundation held online October 14-18, 2020.
According to the TCT Connect press release, the ultra–low-profile fixed-wire and rapid exchange DES systems used in the OPTIMIZE trial are designed to facilitate TR access and DS, potentially reducing the time and cost of PCI. The novel Slender IDS combines a cobalt-chromium platform and bioresorbable amino acid-based (PEA) drug carrier-eluting sirolimus mounted on a low-compliant balloon with an integrated 0.014-inch guidewire (Asahi-Intecc). The same DES used with Slender IDS was also used with a rapid-exchange system (Direct RX, Svelte Medical Systems) in the study.
As summarized by TCT Connect, OPTIMIZE was a prospective, single-blind, randomized, international, multicenter IDE trial comparing the new stent to existing everolimus-eluting stents (Xience [Abbott] or Promus [Boston Scientific]) in 1,639 patients with ischemic heart disease with three or less de novo stenotic lesions (length ≤ 34 mm) in two or less native coronary arteries with reference vessel diameter (RVD) 2.25–4.00 mm amenable to percutaneous coronary intervention. The primary endpoint, target lesion failure (TLF), was powered for noninferiority at 12 months.
The study was composed of 1,639 patients (male, 72%; diabetic, 30%; acute coronary syndrome, 57%; mean age, 65.4 years) with 1,988 lesions (Type B2/C, 74%; moderate-severely calcified, 36%; vessel angulation > 45°, 20%; mean stenosis, 64%; lesion length, 14.6 mm; RVD, 2.78 mm). The patients were 1:1 randomized at 74 investigative sites in the United States (57%), Europe (34%), and Japan (9%) from January 2018 to June 2019.
At 12 months, the TLF rate was 10.3% in the Svelte group and 9.5% in the Xience/Promus group (difference = 0.8% [-inf, 3.8%]; Pnoninferiority = .034 which was above the prespecified 0.025 threshold for noninferiority).
No differences were observed between the two groups for the secondary endpoint of 12-month components of TLF: clinically indicated target lesion revascularization, 1.52% versus 1.93% (P = .57); cardiac death, 0.25% versus 0.26% (P = 1.00); and TVMI, 9.31% versus 8.22% (P = .48).
“Based on the prespecified study statistical analysis plan, Svelte DES did not quite meet the threshold for non-inferiority using the prespecified absolute noninferiority margin,” commented Dr. Kereiakes in the TCT Connect announcement. “However, independent analyses of OPTIMIZE results using either a comparable relative noninferiority margin with the protocol definition of MI or the SCAI definition of MI clearly demonstrate noninferiority of Svelte DES to Xience/Promus."
Dr. Kereiakes further stated, "The high TVMI rates observed in both treatment groups was due to the use of high-sensitivity troponin biomarkers in 25% of OPTIMIZE subjects. High TVMI rates drove the higher than expected TLF rates, which effectively underpowered the study. Other clinical outcomes were excellent, with very low rates of TLR and stent thrombosis."
"Standardization of IDE study definitions and biomarkers used in assessment of TVMI is urgently needed as evolving changes in biomarker selection will impact the size and integrity of future pivotal DES trials,” concluded Dr. Kereiakes.