Sex-based outcomes after PCI in highbleeding risk patients: Results from the onyx one clear trial

BACKGROUND: While dual antiplatelet therapy (DAPT) constitutes the cornerstone of post-PCI pharmacotherapy, duration of DAPT in high bleeding risk (HBR) patients has not been fully defined especially with regard to sex. The results from the Onyx ONE Clear trial demonstrated favorable safety and efficacy after PCI with 1-month dual antiplatelet therapy (DAPT) in HBR patients treated with Resolute Onyx drug-eluting stents (DES). We sought to evaluate impact of sex on clinical outcomes in this trial. METHODS: In this prespecified subgroup analysis from Onyx ONE Clear, patients were divided into 2 groups according to sex. Primary endpoint was cardiac death or myocardial infarction (MI) from 1 month to 1 year. RESULTS: A total of 487 female patients (32%) and 1019 males (68%) were free from major ischemic events 1-month after PCI and were transitioned to single antiplatelet therapy.Women were older (p<0.001), had more HBR criteria (p=0.02), and higher rates of moderate/severe calcific lesions (p=0.03) compared to men. Men had higher rates of previous MI (p=0.003), atrial fibrillation (p=0.001), and multivessel coronary artery disease (p<0.001). Clinical outcomes between 1 and 12 months are shown in (Figure) and were similar for males and females except for target vessel revascularization which was greater for males (p=0.04). CONCLUSIONS: In HBR patients treated with Resolute Onyx DES and an abbreviated DAPT course of one month, rates of the primary endpoint of cardiac death or MI between 1 and 12 months were low and did not show any sex-based differences. These data support the use of an abbreviated DAPT regimen in men and women with HBR after PCI with Resolute Onyx DES.

Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

De novo coronary lesions treated with the novel polymer-freeBiolimus-A9 coated stents: four- and twelve-month angiographicresults from the prospective, randomised, multicentreBIOFREEDOM clinical trial

Aims: We report the results of the first-in-man evaluation of the BioFreedom (BF)Biolimus A9 (BA9) coated stent (Biosensors Int., Singapore), available in 2different formulations: standard dose (SD: 15.6 μg/mm) and low dose (LD: 7.8μg/mm).Methods and results: A total of 182 pts w/ single lesion were included in theprospective, multicenter (4 sites in Germany), randomised (1:1:1 ratio)BIOFREEDOM trial. Pts were treated with the BF-SD (n=60), BF-LD (n=62) vs.Taxus paclitaxel-eluting stents (PES) (n=60). Lesion criteria were native vessels2.25-3.0 mm in diameter, and <14 mm in length. Overall, pts were divided into 2cohorts w/ similar randomisation ratio: 1st cohort (n=75), enrolled Sep/08-Jan/09(angiographic FU at 4-month); and 2 cohort (n=107), enrolled Jan-Jun/09(angiographic FU at 12-month). Primary endpoint was in-stent late lumen loss(LLL) (non-inferiority, margin=0.24 mm) at 12-month FU (2nd cohort). Baselineclinical/angiographic characteristics were comparable among the 3 groups; 38% oflesions were located in LAD, and all pts achieved angiographic success. At4-month FU (1 cohort), QCA results showed significant decrease in in-stent LLL w/BF-SD and BF-LD vs. PES: 0.08 and 0.12 vs. 0.37mm (p<0.0001 for BF-SD vs.PES; p=0.002 for BF-LD vs. PES); at 12-month, similar results were foundincluding in-stent LLL of 0.17 and 0.22 vs. 0.35 mm for BF-SD and BF-LD vs. PES(p=0.001 for BF-SD vs. PES; p=0.21 for BF-LD vs. PES – p values fornon-inferiority). In addition, the rates of major adverse cardiac events at 12-monthfollow-up were 6.1% in BF-SD, 11.6% in BF-LD, and 5.5% in PES, including targetlesion revascularisation rates of 1.8%, 10% and 5.5% for BF-SD, BF-LD andPES, respectively. Importantly, there were neither death nor stent thrombosis(ARC) up to 12 months.Conclusions: The novel BF polymer-free BA9-coated stents showed excellentacute results, and sustained safety and efficacy through 12-month FU.

Future stent drug delivery systems.

Drug-eluting stents (DES) with antiproliferative drugs attached via polymers on the stent surface have reduced in-stent restenosis and repeat revascularization compared with bare metal stent (BMS) across nearly all lesion and patient subsets. However, the small number of patients with in-stent restenosis after DES treatment still exists. Furthermore, concerns about long-term safety of DES are raised, particularly regarding the higher-than-expected late-event thrombosis. There is no doubt that the DES will continue to play a pivotal role in the treatment of coronary artery disease, yet future designs need to incorporate features that reduce thrombosis and promote endothelialization along with maintaining the efficacy. This review focuses on novel generation of DES, discussing new programs, including new antiproliferative agents, novel polymeric and non polymeric stents.