Findings from the SORT-OUT trial, presented at the 30th annual Transcatheter Cardiovascular Therapeutics (TCT) conference 2018 held at San Diego, showed that at 12 months, polymer free Biolimus A9-coated BioFreedom stent was non-inferior to the thin strut, biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population.
Past literature had suggested that a chronic inflammatory response may be activated by the persistence of polymer material on first and second generation drug-eluting stent following completion of drug release. Subsequently, drug-eluting stents with biodegradable polymers were designed. However, in patients with increased bleeding risk during dual antiplatelet therapy, the Biolimus A9-coated BioFreedom stent devoid of polymer, was shown to be superior in comparison to a bare metal stent. Therefore, the primary investigator, Dr. Lisette Okkels Jensen, from Odense University Hospital, Denmark conducted a multicenter, randomized trial in 3150 participants comparing a polymer-free coronary drug-eluting stent with an ultra-thin strut bioreabsorbable polymer-based drug-eluting stent in an all-comers patient population with a non-inferiority margin of 2.1%.
Patients aged 18 years or over with chronic stable coronary artery disease or acute coronary syndromes, and at least one coronary artery lesion with more than 50% diameter stenosis, requiring treatment with a drug-eluting stent were enrolled. They were randomly allocated to treatment groups after diagnostic coronary angiography and before percutaneous coronary intervention. Block randomization by the center was used to assign patients in a 1:1 ratio to receive the polymer-free Biolimus-eluting BIOFREEDOM stent (Biosensors) in one arm or the biodegradable-polymer Sirolimus-eluting ORSIRO stent (Biotronik) in the other. The primary endpoint comprised of target lesion failure which was a composite of cardiac death, myocardial infarction (not related to other than index lesion) or target lesion revascularization (TLR) within 1 year.
“The advantage we saw here exceeds our expectations by far. We’re dealing with events that are so rare that we must be very careful that a play of chance could play a role.”-Dr. Lisette Okkels Jensen, M.D.
Jensen and his colleagues found that at one year, the primary endpoint occurred in 5.3% vs 4.0% for BIOFREEDOM and ORSIRO groups respectively. (p-value for non-inferiority=0.010) The cardiac death rate, MI Rate, and the TLR Rate Ratios were 0.57 (95%CI 0.33-1.01; p=0.055),0.95( 95%CI 0.60-1.49; p=0.81) and 2.77 (95%CI 1.66-6.42 p<0.0001) respectively. These findings established non-inferiority of the polymer free Biolimus A9-coated BioFreedom stent in comparison to the thin strut, biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population. While efficacy was lower in the BioFreedom stent compared to the Orsiro, the study showcased the fact that the BioFreedom stent had similar safety and risk of definite stent thrombosis as the Orsiro stent.
Commenting on the study, Dr. Jensen stated, “The advantage we saw here exceeds our expectations by far. We’re dealing with events that are so rare that we must be very careful that a play of chance could play a role.”
In yet another randomized trial for drug-eluting stents conducted by Clemens von Birgelen et al. in an all-comers population, the novel Resolute Onyx stent was found to be non-inferior to the Orsiro stent for the primary endpoint of safety and efficacy at 1-year. BIONYX is the first randomized study of the Resolute Onyx stent and the very first assessment of its safety and efficacy in all-comers. In this trial, secondary outcomes were favorable, representing a safety signal for both stents. However, the observed very low rate of stent thrombosis in the Resolute Onyx arm warranted further clinical investigation.
Majority of contemporary DES use platforms from a cobalt-chromium alloy which have a limited radiographic visibility. In order to improve visibility using a novel thin strut composite wire platform which has a dense platinum-iridium core, Resolute Onyx was developed. By lowering strut thickness, this could serve to reduce stent thrombosis while preserving radial strength.
“As the study is not powered for rare adverse events, such as stent thrombosis, these data are hypothesis-generating only and should be interpreted with great caution.”- Dr. Clemens von Birgelen, M.D.
The aim of BIONYX was to assess at 1-year follow-up in 2488 patients, in order to gauge whether the safety and efficacy of the novel Zotarolimus-eluting (Resolute Onyx) stent were non-inferior to the reference Orsiro stent. As the latter had most recently outperformed the former best-in-class everolimus-eluting stent in the BIOFLOW V trial, it was chosen to be the reference stent in BIONYX. The study population included many patients with increased clinical, lesion-related, or procedural risk, reflecting the wide spectrum of patients treated in routine clinical practice. The primary endpoint was Target Vessel Failure (TVF) which was a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization at 1-year.
The trial results showed the primary endpoint of TVF in 4.5% in Resolute Onyx as compared to 4.7% of cases in Orsiro (HR 0.75 (0.66 – 1.37), Log-rank p = 0.77). At 1-year follow-up, there was no statistically significant difference between stent groups in the components of Target Vessel Failure (TVF). The rate of definite or probable stent thrombosis in case of Resolute onyx was 0.1% vs Orsiro where it was 0.7%. (HR 0.11 (0.01-0.87) Log-rank p=0.01)
However, the primary investigator, Dr. Clemens von Birgelen cautioned that “As the study is not powered for rare adverse events, such as stent thrombosis, these data are hypothesis-generating only and should be interpreted with great caution.”
To view the interview with Dr. C. Michael Gibson, click here.
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