Bernard Chevalier

Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery Stenosis Six-Month Clinical and Imaging Outcomes

OBJECTIVES The aim of this study was to demonstrate that the prevention of early scaffold area shrinkage of the ABSORB BVS (Rev.1.1, Abbott Vascular, Santa Clara, California) was sustained and not simply delayed by a few months. BACKGROUND With improved scaffold design and modified manufacturing process of its polymer, the second iteration of ABSORB (BVS 1.1) has improved performance to prevent a scaffold area reduction at 6 months. METHODS Fifty-six patients were enrolled and received 57 ABSORB scaffolds. Quantitative coronary angiography, intravascular ultrasound (IVUS), analysis of radiofrequency backscattering, echogenicity and optical coherence tomography (OCT) were performed at baseline and at 12-month follow-up. RESULTS Overall the scaffold area remained unchanged with IVUS as well as with OCT, whereas the radiofrequency backscattering and the echogenicity of the struts decreased by 16.8% (p < 0.001) and 20% (p < 0.001), respectively; more specifically, the strut core area on OCT decreased by 11.4% (p = 0.003). Despite the absence of scaffold area loss, pharmacological vasomotion was restored. On an intention-to-treat basis, the angiographic late lumen loss amounted to 0.27 ± 0.32 mm with an IVUS relative decrease in minimal lumen area of 1.94% (p = 0.12), without significant changes in mean lumen area. The OCT at follow-up showed that 96.69% of the struts were covered and that malapposition, initially observed in 18 scaffolds was only detected at follow-up in 4 scaffolds. Two patients experienced peri-procedural and iatrogenic myocardial infarction, respectively, whereas 2 underwent repeat intervention, resulting in the major adverse cardiac event rate of 7.1% (4 of 56). CONCLUSIONS The 12-month performance of the second-generation ABSORB bioresorbable everolimus-eluting scaffold justifies the conduct of a randomized trial against current best standards. (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System [BVS EECSS] in the Treatment of Patients With de Novo Native Coronary Artery Lesions; NCT00856856).

A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial

BACKGROUND Despite rapid dissemination of an everolimus-eluting bioresorbable scaffold for treatment for coronary artery disease, no data from comparisons with its metallic stent counterpart are available. In a randomised controlled trial we aimed to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent. Here we report secondary clinical and procedural outcomes after 1 year of follow-up. METHODS In a single-blind, multicentre, randomised trial, we enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb, Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience, Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. The co-primary endpoints of this study are vasomotion (change in mean lumen diameter before and after nitrate administration at 3 years) and difference between minimum lumen diameter (after nitrate administration) after the index procedure and at 3 years. Secondary endpoints were procedural performance assessed by quantitative angiography and intravascular ultrasound; composite clinical endpoints based on death, myocardial infarction, and coronary revascularisation; device and procedural success; and angina status assessed by the Seattle Angina Questionnaire and exercise testing at 6 and 12 months. Cumulative angina rate based on adverse event reporting was analysed post hoc. This trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the bioresorbable scaffold group (335 patients, 364 lesions) or the metallic stent group (166 patients, 182 lesions). Dilatation pressure and balloon diameter at the highest pressure during implantation or postdilatation were higher and larger in the metallic stent group, whereas the acute recoil post implantation was similar (0.19 mm for both, p=0.85). Acute lumen gain was lower for the bioresorbable scaffold by quantitative coronary angiography (1.15 mm vs 1.46 mm, p<0.0001) and quantitative intravascular ultrasound (2.85 mm(2)vs 3.60 mm(2), p<0.0001), resulting in a smaller lumen diameter or area post procedure. At 1 year, however, cumulative rates of first new or worsening angina from adverse event reporting were lower (72 patients [22%] in the bioresorbable scaffold group vs 50 [30%] in the metallic stent group, p=0.04), whereas performance during maximum exercise and angina status by SAQ were similar. The 1-year composite device orientated endpoint was similar between the bioresorbable scaffold and metallic stent groups (16 patients [5%] vs five patients [3%], p=0.35). Three patients in the bioresorbable scaffold group had definite or probable scaffold thromboses (one definite acute, one definite sub-acute, and one probable late), compared with no patients in the metallic stent group. There were 17 (5%) major cardiac adverse events in the bioresorbable scaffold group compared with five (3%) events in the metallic stent group, with the most common adverse events being myocardial infarction (15 cases [4%] vs two cases [1%], respectively) and clinically indicated target-lesion revascularisation (four cases [1%] vs three cases [2%], respectively). INTERPRETATION The everolimus-eluting bioresorbable scaffold showed similar 1-year composite secondary clinical outcomes to the everolimus-eluting metallic stent. FUNDING Abbott Vascular.

Transfemoral aortic valve implantation new criteria to predict vascular complications.

OBJECTIVES This study sought to evaluate the incidence, impact, and predictors of vascular complications in transcatheter aortic valve implantation (TAVI). BACKGROUND Vascular complications increase morbidity and mortality in transfemoral TAVI; however, there remains a paucity of data describing these serious events. METHODS We performed a prospective cohort study of 130 consecutive transfemoral TAVI recipients. Vascular complications were defined by the Valve Academic Research Consortium (VARC) criteria. The ratio of the sheath outer diameter (in millimeters) to the minimal femoral artery diameter (in millimeters) defined the sheath to femoral artery ratio (SFAR). RESULTS In our cohort of elderly patients (83.3 ± 5.9 years), the logistic EuroScore was 25.8% ± 11.9%. The Edwards valve was used in 102 cases (18- to 24-F) and the CoreValve in 27 (18-F). The minimal femoral artery diameter was 8.17 ± 1.14 mm, and the calcification (0 to 3) and tortuosity scores (0 to 3) were 0.58 ± 0.72 and 0.28 ± 0.53, respectively. The mean sheath diameter was 8.10 ± 0.82 mm, and the mean SFAR was 0.99 ± 0.16. Vascular complications occurred in 27.6% (VARC major: 17.3%, minor: 10.2%), and major vascular complications predicted 30-day mortality (22.7% vs. 7.6%, p = 0.049). The SFAR (hazard ratio [HR]: 186.20, 95% confidence interval [CI]: 4.41 to 7,855.11), center experience (HR: 3.66, 95% CI: 1.17 to 11.49), and femoral calcification (HR: 3.44, 95% CI: 1.16 to 10.17) predicted major complications by multivariate analysis. An SFAR threshold of 1.05 (area under the curve = 0.727) predicted a higher rate of VARC major complications (30.9% vs. 6.9%, p = 0.001) and 30-day mortality (18.2% vs. 4.2%, p = 0.016). CONCLUSIONS Vascular complications in transfemoral TAVI are relatively frequent. VARC major vascular complications increase 30-day mortality and are predicted by experience, femoral calcification, and SFAR. Routine application of SFAR will improve patient selection for transfemoral TAVI and may improve outcome.

Intracoronary Stent Implantation Without Ultrasound Guidance and With Replacement of Conventional Anticoagulation by Antiplatelet Therapy 30-Day Clinical Outcome of the French Multicenter Registry

BACKGROUND Stenting reduces both acute complications of coronary angioplasty and restenosis rates but increases subacute thrombosis rates and hemorrhagic complications when used with coumadin anticoagulation. METHODS AND RESULTS To simplify postcoronary stenting treatment and to reduce these drawbacks, we evaluated the 1-month outcome of a prospective registry of 2900 patients in whom successful coronary artery stenting was performed without coumadin anticoagulation. Patients received 100 mg/d aspirin and 250 mg/d ticlopidine for 1 month. Low-molecular-weight heparin (LMWH) treatment was progressively reduced in four consecutive stages, from 1-month treatment to none. Event-free outcome at 1 month was achieved in 2816 patients (97.1%). Major stent-related cardiac events were subacute closure in 51 patients (1.8%), including death in 12 (0.5%), acute myocardial infarction in 17 (0.6%), and coronary artery bypass graft surgery in 9 (0.3%). Stent thrombosis was more frequent with balloon size of < 3.0 mm (< or = 2.5 mm, 10%; 3.0 mm, 2.3%; > or = 3.5 mm, 1.0%; P < .001), bail-out situations (6.67% versus 1.38%, P < .001), and patients with unstable angina or acute myocardial infarction (2.2% versus 1.12%, P = .02). Bleeding complications that required transfusion, surgical repair, or both occurred in 55 patients (1.9%). Bleeding complications were related to female gender (4.0% versus 1.51%, P < .001), duration of LMWH treatment (3.83% in phase II/III versus 0.69% in phase IV/V, P < .001), sheath size (6F, 0.52%; 7F, 1.04%; > or = 8F, 4.23%; P < .001), bail-out situations (4.76% versus 1.67%, P < .01), and saphenous graft stenting (4.38% versus 1.75%, P = .04). CONCLUSIONS These results suggest that poststenting treatment by ticlopidine/aspirin is an effective alternative to coumadin anticoagulation, achieving low rates of subacute closure and bleeding complications. LMWH treatment does not improve subacute reocclusion rates but increases bleeding complications. Furthermore, as bleeding complications were independently related to sheath size, we suggest that stenting with 6F guiding catheters may prevent local complications. Furthermore, the ticlopidine/aspirin combination allows a low-cost stenting strategy without ultrasound assessment of stent deployment and permits short inhospital stay.

Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial.

Background—The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis. Methods and Results—On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 &mgr;g/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9±26.7% in controls (n=34) and 14.2±16.6% in the 2.7-&mgr;g/mm2 group (n=31; P =0.006). Late loss decreased from 0.73±0.73 to 0.11±0.50 mm (P =0.002). Binary restenosis (≥50% at follow-up) decreased from 20.6% to 3.2% (P =0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P =NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only. Conclusions—Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 &mgr;g/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects.

Evaluation of the Second Generation of a Bioresorbable Everolimus Drug-Eluting Vascular Scaffold for Treatment of De Novo Coronary Artery StenosisClinical Perspective

Background— The first generation of the bioresorbable everolimus drug-eluting vascular scaffold showed signs of shrinkage at 6 months, which largely contributed to late luminal loss. Nevertheless, late luminal loss was less than that observed with bare metal stents. To maintain the mechanical integrity of the device up to 6 months, the scaffold design and manufacturing process of its polymer were modified. Methods and Results— Quantitative coronary angiography, intravascular ultrasound with analysis of radiofrequency backscattering, and as an optional assessment, optical coherence tomography (OCT) were performed at baseline and at a 6-month follow-up. Forty-five patients successfully received a single bioresorbable everolimus drug-eluting vascular scaffold. One patient had postprocedural release of myocardial enzyme without Q-wave occurrence; 1 patient with OCT-diagnosed disruption of the scaffold caused by excessive postdilatation was treated 1 month later with a metallic drug-eluting stent. At follow-up, 3 patients declined recatheterization, 42 patients had quantitative coronary angiography, 37 had quantitative intravascular ultrasound, and 25 had OCT. Quantitative coronary angiography disclosed 1 edge restenosis (1 of 42; in-segment binary restenosis, 2.4%). At variance with the ultrasonic changes seen with the first generation of bioresorbable everolimus drug-eluting vascular scaffold at 6 months, the backscattering of the polymeric struts did not decrease over time, the scaffold area was reduced by only 2.0% with intravascular ultrasound, and no change was noted with OCT. On an intention-to-treat basis, the late lumen loss amounted to 0.19±0.18 mm with a limited relative decrease in minimal luminal area of 5.4% on intravascular ultrasound. OCT showed at follow-up that 96.8% of the struts were covered and that malapposition of at least 1 strut, initially observed in 12 scaffolds, was detected at follow-up in only 3 scaffolds. Mean neointimal growth measured by OCT between and on top of the polymeric struts equaled 1.25 mm2, or 16.6% of the scaffold area. Conclusion— Modified manufacturing process of the polymer and geometric changes in the polymeric platform have substantially improved the medium-term performance of this new generation of drug-eluting scaffold to become comparable to those of current drug eluting stents. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00856856.

Adjunctive manual thrombectomy improves myocardial perfusion and mortality in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: a meta-analysis of randomized trials

AIMS The benefits of adjunctive mechanical devices to prevent distal embolization in patients with acute myocardial infarction (AMI) are still a matter of debate. Growing interests are on manual thrombectomy devices as compared with other mechanical devices. In fact, they are inexpensive and user-friendly devices, and thus represent an attractive strategy. The aim of the current study was to perform an updated meta-analysis of randomized trials conducted with adjunctive manual thrombectomy devices to prevent distal embolization in AMI. METHODS AND RESULTS The literature was scanned by formal searches of electronic databases [MEDLINE, CENTRAL, EMBASE, and The Cochrane Central Register of Controlled trials (http://www.mrw.interscience.wiley.com/cochrane/Cochrane_clcentral_articles_fs.html)] from January 1990 to May 2008, the scientific session abstracts (from January 1990 to May 2008) and oral presentation and/or expert slide presentations (from January 2002 to May 2008) [on transcatheter coronary therapeutics (TCT), AHA (American Heart Association), ESC (European Society of Cardiology), ACC (American College of Cardiology) and EuroPCR websites]. We examined all randomized trials on adjunctive mechanical devices to prevent distal embolization in AMI. The following keywords were used: randomized trial, myocardial infarction, reperfusion, primary angioplasty, rescue angioplasty, thrombectomy, thrombus aspiration, manual thrombectomy, Diver catheter, Pronto catheter, Export catheter, thrombus vacuum aspiration catheter. Information on study design, type of device, inclusion and exclusion criteria, number of patients, and clinical outcome was extracted by two investigators. Disagreements were resolved by consensus. A total of nine trials with 2417 patients were included [1209 patients (50.0%) in the manual thrombectomy device group and 1208 (50%) in the control group]. Adjunctive manual thrombectomy was associated with significantly improved postprocedural TIMI (thrombolysis in myocardial infarction) 3 flow (87.1 vs. 81.2%, P < 0.0001), and postprocedural MBG 3 (myocardial blush grade 3) (52.1 vs. 31.7%, P < 0.0001), less distal embolization (7.9 vs. 19.5%, P < 0.0001), and significant benefits in terms of 30-day mortality (1.7 vs. 3.1%, P = 0.04). CONCLUSION This meta-analysis demonstrates that, among patients with AMI treated with percutaneous coronary intervention, the use of adjunctive manual thrombectomy devices is associated with better epicardial and myocardial perfusion, less distal embolization and significant reduction in 30-day mortality. Thus, adjunctive manual thrombectomy devices, if not anatomically contraindicated, should be routinely used among STEMI (ST-segment elevation myocardial infarction) patients undergoing primary angioplasty.

Evaluation of the Second Generation of a Bioresorbable Everolimus-Eluting Vascular Scaffold for the Treatment of De Novo Coronary Artery Stenosis

OBJECTIVES The aim of this study was to demonstrate that the prevention of early scaffold area shrinkage of the ABSORB BVS (Rev.1.1, Abbott Vascular, Santa Clara, California) was sustained and not simply delayed by a few months. BACKGROUND With improved scaffold design and modified manufacturing process of its polymer, the second iteration of ABSORB (BVS 1.1) has improved performance to prevent a scaffold area reduction at 6 months. METHODS Fifty-six patients were enrolled and received 57 ABSORB scaffolds. Quantitative coronary angiography, intravascular ultrasound (IVUS), analysis of radiofrequency backscattering, echogenicity and optical coherence tomography (OCT) were performed at baseline and at 12-month follow-up. RESULTS Overall the scaffold area remained unchanged with IVUS as well as with OCT, whereas the radiofrequency backscattering and the echogenicity of the struts decreased by 16.8% (p < 0.001) and 20% (p < 0.001), respectively; more specifically, the strut core area on OCT decreased by 11.4% (p = 0.003). Despite the absence of scaffold area loss, pharmacological vasomotion was restored. On an intention-to-treat basis, the angiographic late lumen loss amounted to 0.27 ± 0.32 mm with an IVUS relative decrease in minimal lumen area of 1.94% (p = 0.12), without significant changes in mean lumen area. The OCT at follow-up showed that 96.69% of the struts were covered and that malapposition, initially observed in 18 scaffolds was only detected at follow-up in 4 scaffolds. Two patients experienced peri-procedural and iatrogenic myocardial infarction, respectively, whereas 2 underwent repeat intervention, resulting in the major adverse cardiac event rate of 7.1% (4 of 56). CONCLUSIONS The 12-month performance of the second-generation ABSORB bioresorbable everolimus-eluting scaffold justifies the conduct of a randomized trial against current best standards. (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System [BVS EECSS] in the Treatment of Patients With de Novo Native Coronary Artery Lesions; NCT00856856).

Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial

BACKGROUND No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of recovered vasomotion of the scaffolded vessel. METHODS The ABSORB II trial is a prospective, randomised, active-controlled, single-blind, parallel two-group, multicentre clinical trial. We enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients (2:1) to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. At 3 year follow-up, the primary endpoint was superiority of the Absorb bioresorbable scaffold versus the Xience metallic stent in angiographic vasomotor reactivity after administration of intracoronary nitrate. The co-primary endpoint is the non-inferiority of angiographic late luminal loss. For the endpoint of vasomotion, the comparison was tested using a two-sided t test. For the endpoint of late luminal loss, non-inferiority was tested using a one-sided asymptotic test, against a non-inferiority margin of 0·14 mm. The trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the Absorb group (335 patients, 364 lesions) or the Xience group (166 patients, 182 lesions). The vasomotor reactivity at 3 years was not statistically different (Absorb group 0·047 mm [SD 0·109] vs Xience group 0·056 mm [0·117]; psuperiority=0·49), whereas the late luminal loss was larger in the Absorb group than in the Xience group (0·37 mm [0·45] vs 0·25 mm [0·25]; pnon-inferiority=0·78). This difference in luminal dimension was confirmed by intravascular ultrasound assessment of the minimum lumen area (4·32 mm2 [SD 1·48] vs 5·38 mm2 [1·51]; p<0·0001). The secondary endpoints of patient-oriented composite endpoint, Seattle Angina Questionnaire score, and exercise testing were not statistically different in both groups. However, a device-oriented composite endpoint was significantly different between the Absorb group and the Xience group (10% vs 5%, hazard ratio 2·17 [95% CI 1·01-4·70]; log-rank test p=0·0425), mainly driven by target vessel myocardial infarction (6% vs 1%; p=0·0108), including peri-procedural myocardial infarction (4% vs 1%; p=0·16). INTERPRETATION The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non-inferior late luminal loss for the Absorb bioresorbable scaffold with respect to the metallic stent, which was found to have significantly lower late luminal loss than the Absorb scaffold. A higher rate of device-oriented composite endpoint due to target vessel myocardial infarction, including peri-procedural myocardial infarction, was observed in the Absorb group. The patient-oriented composite endpoint, anginal status, and exercise testing, were not statistically different between both devices at 3 years. Future studies should investigate the clinical impact of accurate intravascular imaging in sizing the device and in optimising the scaffold implantation. The benefit and need for prolonged dual antiplatelet therapy after bioresorbable scaffold implantation could also become a topic for future clinical research. FUNDING Abbott Vascular.

Dynamics of vessel wall changes following the implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months

AIMS To assess observations with multimodality imaging of the Absorb bioresorbable everolimus-eluting vascular scaffold performed in two consecutive cohorts of patients who were serially investigated either at 6 and 24 months or at 12 and 36 months. METHODS AND RESULTS In the ABSORB multicentre single-arm trial, 45 patients (cohort B1) and 56 patients (cohort B2) underwent serial invasive imaging, specifically quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), radiofrequency backscattering (IVUS-VH) and optical coherence tomography (OCT). Between one and three years, late luminal loss remained unchanged (6 months: 0.19 mm, 1 year: 0.27 mm, 2 years: 0.27 mm, 3 years: 0.29 mm) and the in-segment angiographic restenosis rate for the entire cohort B (n=101) at three years was 6%. On IVUS, mean lumen, scaffold, plaque and vessel area showed enlargement up to two years. Mean lumen and scaffold area remained stable between two and three years whereas significant reduction in plaque behind the struts occurred with a trend toward adaptive restrictive remodelling of EEM. Hyperechogenicity of the vessel wall, a surrogate of the bioresorption process, decreased from 23.1% to 10.4% with a reduction of radiofrequency backscattering for dense calcium and necrotic core. At three years, the count of strut cores detected on OCT increased significantly, probably reflecting the dismantling of the scaffold; 98% of struts were covered. In the entire cohort B (n=101), the three-year major adverse cardiac event rate was 10.0% without any scaffold thrombosis. CONCLUSIONS The current investigation demonstrated the dynamics of vessel wall changes after implantation of a bioresorbable scaffold, resulting at three years in stable luminal dimensions, a low restenosis rate and a low clinical major adverse cardiac events rate. CLINICAL TRIAL REGISTRATION INFORMATION http://www.clinicaltrials.gov/ct2/show/NCT00856856.