12-month Target Lesion Failure Research Articles

Bioadaptor implant versus contemporary drug-eluting stent in percutaneous coronary interventions in Sweden (INFINITY-SWEDEHEART): a single-blind, non-inferiority, registry-based, randomised controlled trial.

Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population. INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4·2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing. Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69·5 years (IQR 61·2-75·6), 575 (24·0%) of 2399 patients were female, and 1824 (76·0%) were male (data on race and ethnicity were not collected), and 1838 (76·6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2·4%) of 1189 assessable patients in the bioadaptor group versus 33 (2·8%) of 1192 assessable patients in the DES group, with a risk difference of -0·41% (95% CI -1·94 to 1·11; pnon-inferiority<0·0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0·3% (with events in three of 1170 patients) in the bioadaptor group versus 1·7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0·19 [95% CI 0·06 to 0·65]; p=0·0079), of target vessel failure were 0·8% (events in eight of 1167) versus 2·5% (events in 23 of 1174; 0·35 [0·16 to 0·79]; p=0·011), and of target lesion failure in patients with acute coronary syndrome were 0·3% (events in two of 906) versus 1·8% (events in 12 of 895; 0·17 [0·04 to 0·74]; p=0·018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0·7%] of 1201 in the bioadaptor group vs six [0·5%] of 1198 in the DES group; difference in event rates of 0·16% [95% CI -0·50 to 0·83]). Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing device-related events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings. Elixir Medical.

Quantitative Coronary Angiography vs Intravascular Ultrasonography to Guide Drug-Eluting Stent Implantation

Although intravascular ultrasonography (IVUS) guidance promotes favorable outcomes after percutaneous coronary intervention (PCI), many catheterization laboratories worldwide lack access. To investigate whether systematic implementation of quantitative coronary angiography (QCA) to assist angiography-guided PCI could be an alternative strategy to IVUS guidance during stent implantation. This randomized, open-label, noninferiority clinical trial enrolled adults (aged ≥18 years) with chronic or acute coronary syndrome and angiographically confirmed native coronary artery stenosis requiring PCI. Patients were enrolled in 6 cardiac centers in Korea from February 23, 2017, to August 23, 2021, and follow-up occurred through August 25, 2022. All principal analyses were performed according to the intention-to-treat principle. After successful guidewire crossing of the first target lesion, patients were randomized in a 1:1 ratio to receive either QCA- or IVUS-guided PCI. The primary outcome was target lesion failure at 12 months, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. The trial was designed assuming an event rate of 8%, with the upper limit of the 1-sided 97.5% CI of the absolute difference in 12-month target lesion failure (QCA-guided PCI minus IVUS-guided PCI) to be less than 3.5 percentage points for noninferiority. The trial included 1528 patients who underwent PCI with QCA guidance (763; mean [SD] age, 64.1 [9.9] years; 574 males [75.2%]) or IVUS guidance (765; mean [SD] age, 64.6 [9.5] years; 622 males [81.3%]). The post-PCI mean (SD) minimum lumen diameter was similar between the QCA- and IVUS-guided PCI groups (2.57 [0.55] vs 2.60 [0.58] mm, P = .26). Target lesion failure at 12 months occurred in 29 of 763 patients (3.81%) in the QCA-guided PCI group and 29 of 765 patients (3.80%) in the IVUS-guided PCI group (absolute risk difference, 0.01 percentage points [95% CI, -1.91 to 1.93 percentage points]; hazard ratio, 1.00 [95% CI, 0.60-1.68]; P = .99). There was no difference in the rates of stent edge dissection (1.2% vs 0.7%, P = .25), coronary perforation (0.2% vs 0.4%, P = .41), or stent thrombosis (0.53% vs 0.66%, P = .74) between the QCA- and IVUS-guided PCI groups. The risk of the primary end point was consistent regardless of subgroup, with no significant interaction. Findings of this randomized clinical trial indicate that QCA and IVUS guidance during PCI showed similar rates of target lesion failure at 12 months. However, due to the lower-than-expected rates of target lesion failure in this trial, the findings should be interpreted with caution. ClinicalTrials.gov Identifier: NCT02978456.

First randomised controlled trial comparing the sirolimus-eluting bioadaptor with the zotarolimus-eluting drug-eluting stent in patients with de novo coronary artery lesions: 12-month clinical and imaging data from the multi-centre, international, BIODAPTOR-RCT

The DynamX™ bioadaptor is the first coronary implant technology with a unique mechanism of unlocking the bioadaptor frame after polymer resorption over 6 months, uncaging the vessel while maintaining a dynamic support to the vessel. It aims to achieve the acute performance of drug-eluting stents (DES) with the advantages of restoration of vessel function. This international, single blinded, randomised controlled (1:1) trial compared a sirolimus-eluting bioadaptor with a contemporary zotarolimus-eluting stent (DES) in 34 hospitals in Europe, Japan and New Zealand. Patients with de novo coronary lesions and absence of acute myocardial infarction were enrolled from January 2021 to Feburary 2022. The implantation of the bioadaptor followed the standards of DES. An imaging subset of 100 patients had angiographic and intravascular ultrasound assessments, and 20 patients additionally optical coherence tomography. Data collection will continue through 5 years, we herein report 12-month data based on an intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT04192747). 445 patients were randomised between January 2021 and February 2022. Device, lesion and procedural success rates, and acute gain were similar amongst the groups. The primary endpoint, 12-month target lesion failure, was 1.8% [95% CI: 0.5; 4.6] (n=4) versus 2.8% [95% CI: 1.0; 6.0] (n=6), pnon-inferiority < 0.001 for the bioadaptor and the DES, respectively (Δ-1.0% [95% CI:-3.3; 1.4]). One definite or probable device thrombosis occurred in each group. The 12-month imaging endpoints showed superior effectiveness of the bioadaptor such as in-device late lumen loss (0.09mm [SD 0.34] versus 0.25mm [SD 0.39], p=0.04), and restored compliance and cyclic pulsatility (%mid in-device lumen area change of 7.5% versus 2.7%, p<0.001). This is the first randomised controlled trial comparing the novel bioadaptor technology against a contemporary DES. The bioadaptor demonstrated similar acute performance and 12-month clinical outcomes, and superior imaging endpoints including restoration of vessel function. The study was funded by Elixir Medical.

Clinical implication of ticagrelor monotherapy in patients with small vessel coronary artery disease: results from the TICO randomized trial.

The aim of this study was to evaluate the efficacy and safety of ticagrelor monotherapy in patients with small vessel disease compared with ticagrelor-based DAPT within the Ticagrelor Monotherapy after 3 Months in the Patients Treated with New Generation Sirolimus Eluting Stent for Acute Coronary Syndrome (TICO) trial population. Reference vessel diameter ≤2.5 mm was considered as small vessel disease. We conducted a comparison of the incidence of target lesion failure (TLF) and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding. TLF was defined as a composite of cardiac death, target lesion myocardial infarction, stent thrombosis, and target lesion revascularization. 652 patients among 3,056 TICO population (21.3%) had small vessel disease. Patients with small vessel disease showed a higher rate of TLF compared to those without small vessel disease (2.9% vs. 1.0%, log-rank p < 0.001). The presence of small vessel disease emerged as an independent predictor for 1-year TLF (HR 2.84, 95% CI 1.54-5.25), while it did not show a significant association with bleeding complications. The 12-month TLF rate was 1.6% for ticagrelor monotherapy after 3-month DAPT, and 4.2% for ticagrelor-based 12-month DAPT (p = 0.059) in patients with small vessel disease (HR 0.38, 95% CI 0.14-1.04, p for interaction = 0.261). The incidence of BARC type 3 or 5 bleeding rate 2.5% for ticagrelor monotherapy after 3-month DAPT, and 5.6% for ticagrelor-based 12-month DAPT (p = 0.052) in patients with small vessel disease (HR 0.44, 95% CI 0.19-1.01, p for interaction = 0.322). In the 3-month landmark analysis, ticagrelor monotherapy significantly reduced BARC type 3 or 5 bleeding in patients with small vessel disease (HR 0.09, 95% CI 0.01-0.69, log-rank p = 0.005) while demonstrating a similar incidence of TLF compared to ticagrelor based 12-month DAPT during the 3-12 months period. There are no significant interactions between the antiplatelet strategy regarding the 12-month incidence of ischemic and bleeding complications. Ticagrelor monotherapy demonstrated a reduction in bleeding complications after a 3-month period of DAPT without increasing the rate of TLF, when compared to ticagrelor-based 12-month DAPT, specifically in patients with small vessel disease. Clinical Trial Registration: www.ClinicalTrials.gov, identifier, NCT02494895.

DynamX sirolimus-eluting Bioadaptor versus the zotarolimus-eluting Resolute Onyx stent in patients with de novo coronary artery lesions: Design and rationale of the multi-center, international, randomized BIOADAPTOR-RCT

BackgroundConventional drug-eluting stents achieve good safety and performance outcomes, but the stents permanently cage the vessel, leading to a non-plateauing rate of clinical events. The DynamX Bioadaptor is designed to reduce these long-term events through unique design features that permit restoring vessel function and physiology through the disengagement of uncaging elements after the resorption of a biodegradable polymer over six months. Promising initial results have been obtained in the DynamX mechanistic study, with excellent safety and effectiveness, positive arterial remodeling, improved vasomotion, compliance, and cyclic pulsatility. We now aim to confirm these findings randomizing the DynamX Bioadaptor against the Resolute Onyx stent. MethodsThis multi-center, international, randomized single-blinded study is conducted in 34 sites across Europe, Japan, and New Zealand and is divided into the European/New Zealand cohort and the Japanese cohort (which includes an imaging subset). It is designed to randomly assign 444 patients (222 per region) in a 1:1 ratio to either the DynamX Bioadaptor or the Resolute Onyx stent. Furthermore, a pharmacokinetic substudy is conducted in 9 patients enrolled in Japan to assess the pharmacokinetics of sirolimus after implantation of the DynamX Bioadaptor. Study follow-up is scheduled at one, six, and 12 months, and annually thereafter for five years; imaging follow-up includes angiographic, intravascular ultrasound, and optical coherence tomography assessments at 12 months in a subset of patients. The primary endpoint is 12-month target lesion failure. ConclusionsThis trial will provide valuable insights into the safety and efficacy of this novel bioadaptor when compared to a contemporary drug-eluting stent. Condensed abstractThe DynamX Sirolimus-Eluting Bioadaptor has unique design features aiming to reduce long-term events after percutaneous coronary intervention by permitting the restoration of vessel function through the freeing of uncaging elements. Promising initial results have been obtained in the DynamX mechanistic study. This trial aims to confirm these findings in a randomized setting. The European/ New Zealand and Japanese cohorts were designed to randomly assign 444 subjects in a 1:1 ratio to either the DynamX Bioadaptor or the Resolute Onyx stent. Furthermore, a pharmacokinetic substudy is conducted in 9 patients enrolled in Japan to assess the pharmacokinetics of sirolimus.

The Supreme Biodegradable Polymer DES in Acute and Chronic Coronary Syndromes: A PIONEER III Substudy.

The PIONEER III trial demonstrated noninferiority of 12-month target lesion failure (TLF) with the Supreme DES (Sinomed), a thin-strut cobalt-chromium, biodegradable polymer, sirolimus-eluting stent, compared with a durable polymer, everolimus-eluting (XIENCE/PROMUS) stent (DP-EES). The relative safety and effectiveness of the Supreme DES in patients with acute coronary syndromes (ACS) and those with chronic coronary syndromes (CCS) is not known. PIONEER III was a prospective, multicenter, international, 2:1 randomized trial stratified by clinical presentation. The primary end point was TLF at 12 months (a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization). A total of 1628 patients were enrolled, including 41% of patients with ACS (unstable angina and non-ST-elevation myocardial infarction) randomized to Supreme DES (n = 441) versus DP-EES (n = 232) and 59% of patients with CCS randomized to Supreme DES (n = 645) versus DP-EES (n = 310). Patients with ACS were younger, fewer presented with less diabetes, hypertension, and previous revascularization, but more were current smokers. The primary end point of TLF (6.4% vs 4.4%; P = .1), major adverse cardiac events (8.5% vs 6.5%; P = .16), and stent thrombosis (0.4% vs 0.9%; P = .25) at 12 months were similar in the ACS and CCS groups. There was no difference in TLF at 12 months between Supreme DES and DP-EES among patients with ACS (6.6% vs 6.0%; P = .89) and those with CCS (4.5% vs 4.3%; P = .83); interaction P = .51 for TLF by clinical presentation. Compared with the DP-EES, the Supreme DES seemed safe and effective with a similar TLF at 12 months in both patients with ACS and those with CCS.

Sirolimus-coated balloon versus everolimus-eluting stent in de novo coronary artery disease: Rationale and design of the TRANSFORM II randomized clinical trial.

Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is a widely adopted strategy for the treatment of de novo coronary artery disease. DES implantation conveys an inherent risk for short- and long-term complications, including in-stent restenosis and stent thrombosis. Drug-coated balloons are emerging as an alternative approach to fulfill the "leaving nothing behind" principle and avoid long-term DES-related complications. TRANSFORM II is an investigator-initiated, multicenter, noninferiority, randomized clinical trial, testing a sirolimus-coated balloon (SCB) versus the standard of care for native coronary vessels with a 2-3 mm diameter, in terms of 12-month target lesion failure (TLF; primary endpoint) and net adverse cardiovascular events (coprimary endpoint). Patients undergoing PCI will be randomized to be treated with either SCB or new-generation everolimus-eluting stent and will be followed up clinically for up to 60 months. Assuming a TLF rate of 8% at 12 months with DES, a sample size of 1325 patients was chosen to ensure an 80% power to detect a 1.5% lower incidence in the SCB group with a type I error rate of 0.05. The TRANSFORM II trial is registered on clinicaltrials.gov (identification number NCT04893291). Several substudies, including an optical coherence tomography assessment at 9 months (intracoronary imaging substudy), will investigate the study device in different clinical and lesion settings. The randomized TRANSFORM II trial will determine whether a novel SCB is noninferior to a current everolimus-eluting stent when adopted for the treatment of de novo lesions in coronary vessels with a diameter between 2 and 3 mm.

Ultrathin Bioresorbable Polymer Sirolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents: BIOFLOW V Final 5-Year Outcomes.

Randomized trials have demonstrated the superiority of ultrathin strut drug-eluting stents compared with alternative stent designs. Whether these differences persist over late-term follow-up is uncertain. This study sought to compare late-term (5-year) clinical outcomes among patients treated with ultrathin strut (60 µm) bioresorbable polymer sirolimus-eluting stents (BP SES) and thin strut (81 µm) durable polymer everolimus-eluting stents (DP EES). BIOFLOW V (Biotronik Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects with Up to Three De Novo or Restenotic Coronary Artery Lesions V) was an international, 2:1 randomized trial comparing percutaneous coronary intervention with ultrathin strut BP SES versus thin strut DP EES regarding the primary endpoint of 12-month target lesion failure (TLF). Prespecified outcomes through 5 years were assessed. Among 1,334 patients randomized to treatment with BP SES (n = 884) or DP EES (n = 450), the 5-year rates of TLF were 12.3% for BP SES and 15.3% for DP EES (P = 0.108). Revascularization with BP SES was associated with a significantly lower target vessel-related myocardial infarction (6.6% vs 10.3%, P = 0.015) and late/very late definite/probable stent thrombosis (0.3% vs 1.6%, P = 0.021). Ischemia-driven target lesion revascularization was numerically but not significantly lower with BP SES (5.9% vs 7.7%, P = 0.202). Cardiac death rates were 2.6% versus 1.9% (P=0.495) for BP SES and DP EES, respectively. In a large, randomized trial, TLF and the individual outcomes of cardiac death and target lesion revascularization at 5 years were similar among patients treated with BP SES versus DP EES. Both target vessel-related myocardial infarction and late/very late definite/probable stent thrombosis were significantly lower with BP SES. These results confirm the durability of safety and the effectiveness of percutaneous coronary intervention with ultrathin BP SES.

Safety and Effectiveness of the SVELTE Fixed-Wire and Rapid Exchange Bioresorbable-Polymer Sirolimus-Eluting Coronary Stent Systems for the Treatment of Atherosclerotic Lesions: Results of the OPTIMIZE Randomized Study

[Figure: see text].

Rationale and design of a randomized study comparing the agent drug coated balloon to plain old balloon angioplasty in patients with In-stent restenosis

BackgroundDrug-coated balloon (DCB) technology was developed as an alternative treatment for obstructive coronary artery disease (CAD) and in-stent restenosis (ISR). Management of coronary ISR is clinically challenging and frequently encountered in practice. The Agent DCB uses an inactive excipient to effectively deliver a targeted, therapeutic dose of paclitaxel to the vessel wall. Study DesignAGENT IDE is a prospective, multicenter, randomized controlled trial to evaluate superiority of the Agent DCB to balloon angioplasty in treating patients with ISR. A total of 480 patients with ISR of a previously treated lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm will be initially randomized. Subjects presenting with recent myocardial infarction (MI), complex lesions, or thrombus in the target vessel will be excluded. An adaptive group sequential design with one formal interim analysis for sample size re-estimation will be conducted, and the sample size may be increased to a maximum of 600 subjects. The primary endpoint is the rate of 12-month target lesion failure (TLF; composite of any ischemia-driven revascularization of the target lesion (TLR), target vessel related MI, or cardiac death) and will be tested for superiority in the test arm against the control. Functional status and general health-related quality of life will be measured by changes in the EQ-5D scores. Subjects will be followed for 5 years following the index procedure. ConclusionThis study will prospectively evaluate the safety and efficacy of Agent DCB in patients treated for coronary ISR.

Biodegradable polymer-coated versus durable polymer-coated sirolimus-eluting stents: the final 5-year outcomes of the I-LOVE-IT 2 trial.

This analysis presents the final five-year results of the I-LOVE-IT 2 trial, a non-inferiority study comparing a biodegradable polymer (BP) sirolimus-eluting stent (SES) with a durable polymer (DP) SES in patients with coronary artery disease. Overall, 2,737 Chinese patients eligible for coronary stenting were treated with BP-SES or DP-SES in a 2:1 ratio. Patients who were randomised to the BP-SES group were additionally re-randomised to receive either six-month or 12-month dual antiplatelet therapy (DAPT) in a 1:1 ratio. The primary endpoint was 12-month target lesion failure (TLF: cardiac death, target vessel myocardial infarction (MI), or clinically indicated target lesion revascularisation). At five years, the overall follow-up rate was 90.8%, and the cumulative incidence of TLF as the primary endpoint was similar between BP-SES and DP-SES (hazard ratio [HR] 1.01, 95% confidence interval [CI]: 0.79 to 1.28), as was that for the patient-oriented composite endpoint (PoCE: all-cause death, all MI and any revascularisation) (HR 1.03, 95% CI: 0.86 to 1.23), or definite/probable stent thrombosis (ST) (HR 0.91, 95% CI: 0.70 to 1.77). Cumulative events were also similar between the six-month DAPT and 12-month DAPT groups after BP-SES implantation. I-LOVE-IT 2 showed that the five-year safety and efficacy of BP-SES and DP-SES were similar, as were those between six months and 12 months of DAPT after BP-SES implantation.

Ultrathin Bioresorbable-Polymer Sirolimus-Eluting Stents Versus Thin Durable-Polymer Everolimus-Eluting Stents for Coronary Revascularization: 3-Year Outcomes From the Randomized BIOFLOW V Trial

ObjectivesThe aim of this study was to compare late-term clinical outcomes among patients treated with ultrathin-strut (60-μm) bioresorbable-polymer sirolimus-eluting stents (BP SES) and thin-strut (81μm) durable-polymer everolimus-eluting stents (DP EES). BackgroundEmerging evidence from comparative studies of drug-eluting stents demonstrates improved safety and efficacy with ultrathin-strut drug-eluting stents, but limited insight exists regarding late-term outcomes. MethodsBIOFLOW V (Biotronik Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects With Up to Three De Novo or Restenotic Coronary Artery Lesions V) is an international randomized trial comparing coronary revascularization with BP SES and DP EES regarding the primary endpoint of 12-month target lesion failure. Analysis of pre-specified 3-year clinical outcomes was performed. ResultsAmong 1,334 patients randomized to treatment with BP SES (n = 884) or DP EES (n = 450), the 3-year rate of target lesion failure was 8.2% for BP SES and 13.6% for DP EES (p = 0.002), driven by differences in both target vessel myocardial infarction (MI) (5.0% vs. 9.2%; p = 0.003) and clinically driven target lesion revascularization (3.2% vs. 6.7%; p = 0.006). In landmark analysis, significant differences in target vessel MI and target lesion revascularization were observed favoring treatment with BP SES. Definite or probable late or very late stent thrombosis was significantly lower with BP SES (0.1% vs. 1.2%; p = 0.018). Cardiac death or MI rates were 7.7% and 11.7% (p = 0.017) for BP SES and DP EES, respectively. ConclusionsIn a large randomized trial, both target lesion failure and the outcomes of target vessel MI, clinically driven target lesion revascularization, and late or very late stent thrombosis at 3 years were significantly lower among patients treated with BP SES versus DP EES. The results endorse the continued superiority of ultrathin-strut BP SES compared with DP EES. (Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions [BIOFLOW-V]; NCT02389946)

Twelve-month angiographic and clinical outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold and a metallic stent in patients with coronary artery disease

BackgroundRecent studies showed bioresorbable scaffold (BRS) increased risks of late target lesion failure (TLF) and thrombosis. XINSORB scaffold is a poly-L-lactic acid based BRS. MethodsThe study included randomization and registry parts. Eligible patients with one or two de novo lesions were randomly 1:1 assigned to XINSORB scaffold and sirolimus-eluting stent (SES) in randomization part. These patients were clinically and angiographically assessed. In registry part, patients were treated with XINSORB scaffold only and were clinically assessed. The primary endpoint was in-segment late luminal loss (LLL) at 12-month in randomization part. The secondary endpoint was 12-month TLF in all XINSORB-treated patients. ResultsTotal 395 and 798 patients were enrolled in randomization and registry part, respectively. Device success was 98.0% (1069/1091) in all XINSORB-treated and 100% (221/221) in SES-treated lesions. The primary endpoint of in-segment LLL at 12-month was 0.19 ± 0.32 mm in XINSORB and 0.31 ± 0.41 mm in SES (P = 0.003), which met the noninferior margin of 0.195 mm (95% CI: −0.20, −0.04, P ≪ 0.0001). No difference was found in TLF between two devices. In all XINSORB-treated patients, 12-month TLF was 0.8% (8/998), which also met the noninferior margin of 9.0% (95% CI: 0.3%, 1.4%, P ≪ 0.0001). Only one device thrombosis was recorded in all XINSORB-treated patients while none in SES. ConclusionsIn the multicenter clinical trial, XINSORB BRS was noninferior to sirolimus-eluting stent for the primary endpoint of in-segment LLL at 12-month in patients with simple and moderate complex de novo coronary lesions. TLF at 12-month was low and comparable.

Safety and efficacy of the novel sirolimus-eluting bioresorbable scaffold for the treatment of de novo coronary artery disease: One-year results from a prospective patient-level pooled analysis of NeoVas trials.

This prospective, patient-level analysis assessed the safety and efficacy of NeoVas sirolimus-eluting bioresorbable scaffold (BRS) in patients with coronary lesions. Furthermore, to meet China Food and Drug Administration requirements, we conducted an objective performance criterion study by pooling all patients implanted with the NeoVas BRS in a previous randomized controlled trial (RCT) and registry trial. Drug-eluting stent-related permanent vessel caging by metallic struts may lead to several complications associated with percutaneous coronary intervention. BRSs reportedly result in more stent thromboses (ST) in comparison to everolimus-eluting stents. The NeoVas (Lepu Medical, Beijing, China) is a novel sirolimus-eluting poly-l-lactic acid (PLLA)-based BRS whose safety and efficacy remains to be fully elucidated. Patient-level data derived from 1,103 patients with de novo native coronary lesions in the NeoVas RCT (n = 278) and NeoVas registry (n = 825) were prospectively collected, pooled, and analyzed. The primary outcome was 12-month target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven-target lesion revascularization. The patient-oriented composite endpoint (PoCE) of all-cause death, all MI, or any revascularization was also analyzed. The 12-month rate of TLF in 1,103 patients (follow-up rate, 99.8%) was 3.0%, significantly lower than the performance goal of 8.5% (P < 0.0001). Furthermore, 50 (5.4%) PoCEs and five definite/probable ST (0.5%) were recorded. This pooled, patient-level analysis indicates that the NeoVas BRS has promising 1-year efficacy and safety profiles.

Ultrathin Bioresorbable Polymer Sirolimus-Eluting Stents Versus Thin Durable Polymer Everolimus-Eluting Stents

BackgroundCoronary drug-eluting stent development has introduced new metal alloys, changes in stent architecture, and bioresorbable polymers. Whether these advancements improve long-term clinical safety and efficacy has been inconsistent in prior studies. ObjectivesThe authors sought to compare late-term clinical outcomes among patients treated with an ultrathin strut (60 μm) bioresorbable polymer sirolimus-eluting stent (BP SES) and a thin strut (81 μm) durable polymer everolimus-eluting stent (DP EES) in a large randomized trial. MethodsBIOFLOW V (Biotronik Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in the Treatment of Subjects with Up to Three De Novo or Restenotic Coronary Artery Lesions V) was an international randomized trial comparing coronary revascularization with BP SES and DP EES regarding the primary endpoint of 12-month target lesion failure (TLF). Analysis of pre-specified 2-year clinical outcomes was performed. ResultsAmong 1,334 patients randomized to treatment with BP SES (n = 884) or DP EES (n = 450), the 2-year TLF rate was 7.5% for BP SES and 11.9% for DP EES (−4.33% treatment difference; 95% confidence interval: −8.16% to −0.91%; p = 0.015), driven by differences in target vessel myocardial infarction (MI) (5.3% vs. 9.5%; p = 0.01) and ischemia-driven target lesion revascularization (2.6% vs. 4.9%; p = 0.04). Rates of cardiac death or MI were 7.0% versus 10.4% for BP SES and DP EES, respectively (p = 0.047). Late/very late definite stent thrombosis was statistically lower for BP SES compared with DP EES (0.1% vs. 1.0%; p = 0.045). ConclusionsIn a large randomized trial, significant differences in both TLF and target vessel–related MI persisted through 2 years, favoring treatment with BP SES over DP EES. Significantly lower cumulative target lesion revascularization and late/very late stent thrombosis were also observed with BP SES. (Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions [BIOFLOW-V]; NCT02389946)

Percutaneous coronary intervention for treating de-novo lesions in small coronary vessels: initial experience with the Essential paclitaxel-coated balloon.

Paclitaxel-coated balloon (PCB) coronary angioplasty is an alternative treatment for de-novo coronary lesions in small vessels. This study with the new Essential PCB aimed to evaluate early and mid-term clinical outcomes following angioplasty with the Essential PCB in the treatment of de-novo lesions in small vessels. We included all patients who underwent PCB angioplasty for treating de-novo coronary lesions in small vessels (reference diameter <2.5 mm) between October 2015 and June 2016 in 2 centres. The primary endpoint was the 12-month target lesion failure (TLF) rate: a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization. The secondary endpoints were rates of target vessel failure and global major adverse cardiac events (MACE). A total of 71 patients (comprising 71 lesions) were included, with a mean age of 66±11 years. A 56% were diabetic and 70% had an acute coronary syndrome as an indication for coronary revascularization. The mean vessel diameter and lesion length were 2.21±0.41 and 20.7±9.2 mm, respectively. Predilatation was performed in 85.9% of patients. The median diameter, length, and inflation pressure of the Essential balloon were 2.0 [interquartile range (IQR): 2.0-2.5] mm, 20 (IQR: 15-30) mm, and 12±2 atmospheres, respectively. Angiographic success was achieved in 97.2% of cases, and bail-out stenting was required in nine (12.7%) cases. The incidence of TLF at the 12-month follow-up was 4.2%, with a target lesion revascularization rate of 4.2%. Target vessel failure and global MACE rates were 4.2 and 9.9%, respectively. Use of the Essential PCB for treating de-novo coronary lesions in small vessels was safe, with low TLF and MACE rates at the 12-month follow-up.

Treatment effects of systematic two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: rationale and design of a prospective, randomised and multicentre DEFINITION II trial

IntroductionProvisional stenting (PS) for simple coronary bifurcation lesions is the mainstay of treatment. A systematic two-stent approach is widely used for complex bifurcation lesions (CBLs). However, a randomised comparison of...

Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial

The development of coronary drug-eluting stents has included use of new metal alloys, changes in stent architecture, and use of bioresorbable polymers. Whether these advancements improve clinical safety and efficacy has not been shown in previous randomised trials. We aimed to examine the clinical outcomes of a bioresorbable polymer sirolimus-eluting stent compared with a durable polymer everolimus-eluting stent in a broad patient population undergoing percutaneous coronary intervention. BIOFLOW V was an international, randomised trial done in patients undergoing elective and urgent percutaneous coronary intervention in 90 hospitals in 13 countries (Australia, Belgium, Canada, Denmark, Germany, Hungary, Israel, the Netherlands, New Zealand, South Korea, Spain, Switzerland, and the USA). Eligible patients were those aged 18 years or older with ischaemic heart disease undergoing planned stent implantation in de-novo, native coronary lesions. Patients were randomly assigned (2:1) to either an ultrathin strut (60 μm) bioresorbable polymer sirolimus-eluting stent or to a durable polymer everolimus-eluting stent. Randomisation was via a central web-based data capture system (mixed blocks of 3 and 6), and stratified by study site. The primary endpoint was 12-month target lesion failure. The primary non-inferiority comparison combined these data from two additional randomised trials of bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent with Bayesian methods. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02389946. Between May 8, 2015, and March 31, 2016, 4772 patients were recruited into the study. 1334 patients met inclusion criteria and were randomly assigned to treatment with bioresorbable polymer sirolimus-eluting stents (n=884) or durable polymer everolimus-eluting stents (n=450). 52 (6%) of 883 patients in the bioresorbable polymer sirolimus-eluting stent group and 41 (10%) of 427 patients in the durable polymer everolimus-eluting stent group met the 12-month primary endpoint of target lesion failure (95% CI -6·84 to -0·29, p=0·0399), with differences in target vessel myocardial infarction (39 [5%] of 831 patients vs 35 [8%] of 424 patients, p=0·0155). The posterior probability that the bioresorbable polymer sirolimus-eluting stent is non-inferior to the durable polymer everolimus-eluting stent was 100% (Bayesian analysis, difference in target lesion failure frequency -2·6% [95% credible interval -5·5 to 0·1], non-inferiority margin 3·85%, n=2208). The outperformance of the ultrathin, bioresorbable polymer sirolimus-eluting stent over the durable polymer everolimus-eluting stent in a complex patient population undergoing percutaneous coronary intervention suggests a new direction in improving next generation drug-eluting stent technology. BIOTRONIK.

First Report of the Resolute Onyx 2.0-mm Zotarolimus-Eluting Stent for the Treatment of Coronary Lesions With Very Small Reference Vessel Diameter

ObjectivesThe aim of this study was to explore the safety and efficacy of a dedicated drug-eluting stent for the treatment of coronary lesions with very small reference vessel diameter (RVD). BackgroundSmaller RVD is associated with increased risk for restenosis and target lesion failure (TLF) after stent implantation. MethodsThis was a prospective, single-arm, multicenter trial of the Resolute Onyx 2.0-mm zotarolimus-eluting stent. The primary endpoint was 12-month TLF, which was compared with a pre-specified performance goal. Subjects with stable or unstable angina or ischemia, target lesions ≤27 mm in length, and RVD ≥2.0 and <2.25 mm were eligible for enrollment. A subset of subjects underwent follow-up angiography at 13 months post-procedure. ResultsA total of 101 subjects with 104 lesions were enrolled. The mean age was 67.3 ± 9.6 years, 47% of subjects had diabetes, the mean lesion length was 12.6 ± 6.3 mm, and the mean RVD was 1.91 ± 0.26 mm. The rate of TLF at 12 months was 5.0%, fulfilling the pre-specified performance goal of 19% (p < 0.001). The rates of target lesion revascularization and target vessel myocardial infarction were 2.0% and 3.0%, respectively. There were no episodes of stent thrombosis. In-stent late lumen loss was 0.26 ± 0.48 mm, and the rate of binary restenosis was 12.0%. ConclusionsIn this first report of a drug-eluting stent with a dedicated size to treat lesions with RVD <2.25 mm, the Resolute Onyx 2.0-mm zotarolimus-eluting stent was associated with a low rate of TLF and late lumen loss, without a signal for stent thrombosis. This novel-sized drug-eluting stent appears to be a feasible option for the treatment of coronary lesions in extremely small vessels. (Medtronic Resolute Onyx 2.0 mm Clinical Study; NCT02412501)

Impact of six versus 12 months of dual antiplatelet therapy in patients with drug-eluting stent implantation after risk stratification with the residual SYNTAX score: Results from a secondary analysis of the I-LOVE-IT 2 trial.

The optimal duration of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation remains undetermined, especially for those at high risk of cardiac events postprocedure. This study was aimed to investigate the impact of 6 versus 12 months of DAPT after DES implantation based on risk stratification with the residual SYNTAX score (rSS). A total of 2737 patients in the I-LOVE-IT 2 trial were grouped according to rSS status (low rSS [rSS = 0, n = 1474] versus high rSS [rSS > 0, n = 1263]) and DAPT duration (6 months vs. 12 months). The primary endpoint was 12-month target lesion failure (TLF), and the major secondary endpoints were 12-month net adverse clinical events (NACE) and major bleeding. Incidences of TLF (5.2 vs. 7.4%, P = 0.01) and NACE (9.2 vs. 13.4%, P < 0.001) at 12 months were significantly higher in patients with high rSSs compared with patients with low rSSs. Landmark analysis showed that, in patients with high rSS, 12-month DAPT was associated with slightly lower risks of TLF (3.0% vs. 1.6%, P = 0.08) and NACE (7.0 vs. 4.4%, P = 0.054) compared with 6-month DAPT within 6 to 12 months after PCI. Patients with different DAPT durations had similar risks of bleeding both in the low and high rSS groups. Patients with high rSSs have an increased risk of TLF and NACE at 12 months after DES implantation. Twelve-month DAPT might be superior to 6-month DAPT in patients with high rSS for reducing adverse events within 6 to 12 months after PCI without excessive risk of bleeding. © 2017 Wiley Periodicals, Inc.