Jens Wiebe

Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials

BACKGROUNDnBioresorbable coronary stents might improve outcomes of patients treated with percutaneous coronary interventions. The everolimus-eluting bioresorbable vascular scaffold is the most studied of these stent platforms; however, its performance versus everolimus-eluting metallic stents remains poorly defined. We aimed to assess the efficacy and safety of everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents in patients with ischaemic heart disease treated with percutaneous revascularisation.nnnMETHODSnWe searched Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), scientific sessions abstracts, and relevant websites for randomised trials investigating everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents published or posted between Nov 30, 2006, and Oct 12, 2015. The primary efficacy outcome was target lesion revascularisation and the primary safety outcome was definite or probable stent (scaffold) thrombosis. Secondary outcomes were target lesion failure (the composite of cardiac death, target-vessel myocardial infarction, or ischaemia-driven target lesion revascularisation), myocardial infarction, death, and in-device late lumen loss. We derived odds ratios (ORs) and weighted mean differences with 95% CIs, and calculated the risk estimates for the main outcomes according to a random-effects model. This study is registered with PROSPERO, number CRD42015026374.nnnFINDINGSnWe included six trials, comprising data for 3738 patients randomised to receive percutaneous coronary intervention with either an everolimus-eluting bioresorbable vascular scaffold (n=2337) or an everolimus-eluting metallic stent (n=1401). Median follow-up was 12 months (IQR 9-12). Patients treated with bioresorbable vascular scaffolds had a similar risk of target lesion revascularisation (OR 0.97 [95% CI 0.66-1.43]; p=0.87), target lesion failure (1.20 [0.90-1.60]; p=0.21), myocardial infarction (1.36 [0.98-1.89]; p=0.06), and death (0.95 [0.45-2.00]; p=0.89) as those treated with metallic stents. Patients treated with a bioresorbable vascular scaffold had a higher risk of definite or probable stent thrombosis than those treated with a metallic stent (OR 1.99 [95% CI 1.00-3.98]; p=0.05), with the highest risk between 1 and 30 days after implantation (3.11 [1.24-7.82]; p=0.02). Lesions treated with a bioresorbable vascular scaffold had greater in-device late lumen loss than those treated with a metallic stent (weighted mean difference 0.08 [95% CI 0.05-0.12]; p<0.0001).nnnINTERPRETATIONnCompared with everolimus-eluting metallic stents, everolimus-eluting bioresorbable vascular scaffolds had similar rates of repeat revascularisation at 1 year of follow-up, despite inferior mid-term angiographic performance. However, patients treated with a bioresorbable vascular scaffold had an increased risk of subacute stent thrombosis. Studies with extended follow-up in a larger number of patients are needed to fully assess the long-term advantages of everolimus-eluting bioresorbable vascular scaffolds.nnnFUNDINGnNone.

Angiographic and clinical outcomes of patients treated with everolimus-eluting bioresorbable stents in routine clinical practice: Results of the ISAR-ABSORB registry

We aimed to analyze angiographic and clinical results of patients undergoing BRS implantation in a real‐world setting.

Randomized Trial of Polymer-Free Sirolimus- and Probucol-Eluting Stents Versus Durable Polymer Zotarolimus-Eluting Stents: 5-Year Results of the ISAR-TEST-5 Trial.

OBJECTIVESnThe aim of this study was to evaluate the late clinical performance of a polymer-free sirolimus- and probucol-eluting stent compared with a new-generation durable polymer-based zotarolimus-eluting stent.nnnBACKGROUNDnIt was previously shown that polymer-free sirolimus- and probucol-eluting stents were noninferior to zotarolimus-eluting stents at 12 months. However, long-term follow-up of these devices is critical to evaluate late comparative efficacy.nnnMETHODSnIn a clinical trial with minimal exclusion criteria, 3,002 patients were randomly assigned to treatment with polymer-free sirolimus- and probucol-eluting stents versus zotarolimus-eluting stents. The primary endpoint was the combined incidence of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization.nnnRESULTSnAt 5 years, there was no difference in the incidence of the primary endpoint between sirolimus- and probucol-eluting stents and zotarolimus-eluting stents (23.8% vs. 24.2%, respectively; hazard ratio: 0.98; 95% confidence interval: 0.84 to 1.15; p = 0.80). The rates of the individual components of the primary endpoint were also comparable in both groups. The incidence of definite or probable stent thrombosis was low in both groups (1.3% vs. 1.6%, respectively; hazard ratio: 0.86; 95% confidence interval: 0.46 to 1.62; p = 0.64). The rates of any death, myocardial infarction, and revascularization were similar in both groups. Results were consistent across pre-specified subgroups of age, sex, diabetes, and vessel size.nnnCONCLUSIONSnLong-term outcomes of patients treated with polymer-free sirolimus- and probucol-eluting stents compared with a new-generation durable polymer-based zotarolimus-eluting stent were similar. Rates of stent thrombosis were low and comparable in both treatment groups, with few events beyond 12 months. (Efficacy Study of Rapamycin- vs. Zotarolimus-Eluting Stents to Reduce Coronary Restenosis [ISAR-TEST-5]; NCT00598533).

Mechanisms of Very Late Bioresorbable Scaffold Thrombosis : The INVEST Registry

BACKGROUNDnVery late scaffold thrombosis (VLScT) occurs more frequently after bioresorbable scaffold (Absorb BVSxa01.1, Abbott Vascular, Santa Clara, California) implantation than with metallic everolimus-eluting stents.nnnOBJECTIVESnThe purpose of this study was to elucidate mechanisms underlying VLScT as assessed by optical coherence tomography (OCT).nnnMETHODSnThe INVEST (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis) registry is an international consortium of investigators who used OCT to examine patients with VLScT.nnnRESULTSnBetween June 2013 and May 2017, 36 patients with 38 lesions who had VLScT underwent OCT at 19 centers. VLScT occurred at a median of 20xa0months (interquartile range: 16 to 27xa0months) after implantation. At the time of VLScT, 83% of patients received aspirin monotherapy and 17% received dual-antiplatelet therapy. The mechanisms underlying VLScT were (in descending order) scaffold discontinuity (42.1%), malapposition (18.4%), neoatherosclerosis (18.4%), underexpansion or scaffold recoil (10.5%), uncovered struts (5.3%), and edge-related disease progression (2.6%). Discontinuity (odds ratio [OR]: 110; 95% confidence interval [CI]: 73.5 to 173; pxa0< 0.001), malapposed struts (OR: 17.0; 95% CI: 14.8 to 19.7; pxa0< 0.001), and uncovered struts (OR: 7.3; 95% CI: 6.2 to 8.8; pxa0< 0.001) were more frequent in the thrombosed than the nonthrombosed scaffold regions. In 2 of 16 patients with scaffold discontinuity, intercurrent OCT before VLScT provided evidence of circularly apposed scaffold struts with minimal tissue coverage.nnnCONCLUSIONSnThe leading mechanism underlying VLScT was scaffold discontinuity, which suggests an unfavorable resorption-related process, followed by malapposition and neoatherosclerosis. It remains to be determined whether modifications in scaffold design and optimized implantation can mitigate the risk of VLScT. (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis [INVEST]; NCT03180931).

Long-Term Clinical Outcomes of Patients Treated With Everolimus-Eluting Bioresorbable Stents in Routine Practice : 2-Year Results of the ISAR-ABSORB Registry

OBJECTIVESnThe aim of this study was to report clinical outcomes in patients treated in routine practice 2 years after everolimus-eluting bioresorbable stent (BRS) implantation.nnnBACKGROUNDnLong-term results in patients undergoing BRS implantation in routine clinical practice are sparse, and existing evidence from randomized trials considers mostly selected patients.nnnMETHODSnThe ISAR-ABSORB registry enrolled consecutive patients undergoing BRS implantation in routine clinical practice at 2 high-volume centers in Germany. Angiographic follow-up was scheduled after 6 to 8 months and clinical follow-up to 24 months. The primary endpoint was the composite of death, myocardial infarction, or target lesion revascularization, and secondary endpoints included individual components of the primary endpoint and definite stent thrombosis. Event rates were calculated using the Kaplan-Meier method.nnnRESULTSnA total of 419 patients were included. The mean age was 66.6 ± 10.9 years, 31.5% had diabetes, and 39.0% presented with acute coronary syndrome. Forty-nine percent of lesions were considered complex (American College of Cardiology/American Heart Association type B2 or C), and 13.1% were bifurcation lesions. The mean reference vessel diameter was 2.89 ± 0.46 mm. At 2 years, the primary endpoint had occurred in 21.6% of patients: death in 6.3%, myocardial infarction in 3.9%, target lesion revascularization in 16.0%, and definite stent thrombosis in 3.8%.nnnCONCLUSIONSnLong-term follow-up of patients treated with BRS in routine practice showed higher event rates than expected. Future studies are required to determine the impact of changes in implantation technique and to define the optimal duration of dual antiplatelet therapy in these patients.

Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting in Patients With Left Main Coronary Artery Stenosis: A Systematic Review and Meta-analysis

Importance In patients with left main coronary artery (LMCA) stenosis, coronary artery bypass grafting (CABG) has been the standard therapy for several decades. However, some studies suggest that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative. Objective To compare the long-term safety of PCI with drug-eluting stent vs CABG in patients with LMCA stenosis. Data Sources PubMed, Scopus, EMBASE, Web of Knowledge, and ScienceDirect databases were searched from December 18, 2001, to February 1, 2017. Inclusion criteria were randomized clinical trial, patients with LMCA stenosis, PCI vs CABG, exclusive use of drug-eluting stents, and clinical follow-up of 3 or more years. Data Extraction and Synthesis Trial-level hazard ratios (HRs) and 95% CIs were pooled by fixed-effect and random-effects models with inverse variance weighting. Time-to-event individual patient data for the primary end point were reconstructed. Sensitivity analyses according to drug-eluting stent generation and coronary artery disease complexity were performed. Main Outcomes and Measures The primary end point was a composite of all-cause death, myocardial infarction, or stroke at long-term follow-up. Secondary end points included repeat revascularization and a composite of all-cause death, myocardial infarction, stroke, or repeat revascularization at long-term follow-up. Results A total of 4 randomized clinical trials were pooled; 4394 patients were included in the analysis. Of these, 3371 (76.7%) were men; pooled mean age was 65.4 years. According to Grading of Recommendations, Assessment, Development and Evaluation, evidence quality with respect to the primary composite end point was high. Percutaneous coronary intervention and CABG were associated with a comparable risk of all-cause death, myocardial infarction, or stroke both by fixed-effect (HR, 1.06; 95% CI, 0.90-1.24; Pu2009=u2009.48) and random-effects (HR, 1.06; 95% CI, 0.85-1.32; Pu2009=u2009.60) analysis. Sensitivity analyses according to low to intermediate Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score (random-effects: HR, 1.02; 95% CI, 0.74-1.41; Pu2009=u2009.89) and drug-eluting stent generation (first generation: HR, 0.90; 95% CI, 0.68-1.20; Pu2009=u2009.49; second generation: HR, 1.19; 95% CI, 0.82-1.73; Pu2009=u2009.36) were consistent. Kaplan-Meier curve reconstruction did not show significant variations over time between the techniques, with a 5-year incidence of all-cause death, myocardial infarction, or stroke of 18.3% (319 events) in patients treated with PCI and 16.9% (292 events) in patients treated with CABG. However, repeat revascularization after PCI was increased (HR, 1.70; 95% CI, 1.42-2.05; Pu2009<u2009.001). Other individual secondary end points did not differ significantly between groups. Finally, pooled estimates of trials with LMCA stenosis tended overall to differ significantly from those of trials with multivessel coronary artery disease without left main LMCA stenosis. Conclusions and Relevance Percutaneous coronary intervention and CABG show comparable safety in patients with LMCA stenosis and low to intermediate–complexity coronary artery disease. However, repeat revascularization is more common after PCI.

A new novolimus-eluting bioresorbable coronary scaffold: Present status and future clinical perspectives.

The DESolve® scaffold (Elixir Medical Corporation, Sunnyvale, California, USA) is manufactured from a poly-l-lactide based polymer and elutes an anti-proliferative, anti-inflammatory drug, Novolimus from a poly-l-lactide based topcoat mixture. The strut thickness is 150μm and the scaffold has platinum-iridium radiopaque markers at both ends. Radial support is available during the early time period to prevent recoil. The scaffold biodegrades within 1year (>90% reduction in molecular weight) and then completely bioresorbs within 2years. The DESolve® scaffold permits a wide range of expansion with a consequently reduced risk for strut fracture. Lumen and scaffold enlargement is observed within 3-6months in both preclinical and clinical studies potentially allowing for the scaffolded region to respond to vasoactive stimuli. The device has a unique property of self-correction observed in bench top studies, which in clinical practice has the potential to eliminate minor malapposition following deployment.

Post-dilatation after implantation of bioresorbable everolimus- and novolimus-eluting scaffolds: an observational optical coherence tomography study of acute mechanical effects

ObjectivesThe objective was to investigate the acute mechanical effects of post-dilatation on bioresorbable scaffolds (BRS) as determined by optical coherence tomography (OCT).BackgroundPost-dilatation with high-pressure balloons is regarded as a key component of BRS implantation for treatment of coronary artery stenoses. However, the impact of post-dilatation on BRS in vivo has not been thoroughly investigated.MethodsOCT was performed after the implantation procedure of 51 everolimus-eluting or novolimus-eluting polylactic acid-based BRS with (nxa0=xa027) or without non-compliant balloon post-dilatation (nxa0=xa024). The number of malapposed struts, strut fractures, edge dissections, residual in-scaffold area stenosis, and incomplete scaffold apposition area was analyzed over the complete length of each BRS with a spacing of 1xa0mm.ResultsOCT revealed a significantly lower incomplete scaffold apposition area if post-dilatation was performed (0.16xa0±xa00.49xa0mm2 with post-dilatation vs. 2.65xa0±xa02.78xa0mm2 without post-dilatation, pxa0<xa00.001), as well as a significantly lower absolute number of malapposed struts (1xa0±xa02 with post-dilatation vs. 13xa0±xa013 without post-dilatation, pxa0<xa00.001). No significant differences regarding residual in-scaffold area stenosis, strut fracture, edge dissection, symmetry index, or eccentricity index were observed in patients with vs. without post-dilatation.ConclusionPost-dilatation of BRS with non-compliant balloons significantly reduces the number of malapposed struts and incomplete scaffold apposition area without inducing higher rates of edge dissection or strut fracture.

Five-year follow-up of polymer-free sirolimus- and probucol-eluting stents versus new generation zotarolimus-eluting stents in patients presenting with st-elevation myocardial infarction.

Patients with ST‐segment elevation myocardial infarction (STEMI) undergoing drug‐eluting stent (DES) implantation are at increased risk of late adverse events, partly explained by an exaggerated inflammatory reaction to durable‐polymer stent coatings.

TCT-207 Extended validation of a decision tool (DAPT score) in patients randomized to 6 or 12 months dual antiplatelet therapy after percutaneous coronary intervention with predominantly second-generation drug-eluting stents.

TCT-206 Tailoring the Intensity of Antiplatelet Pharmacotherapy to Ischemic and Bleeding Risk: A Cost Optimizing Simulation From PARIS Daniel Leisman, Usman Baber, David Cohen, C. Michael Gibson, Stuart Pocock, Timothy Henry, Philippe Gabriel Steg, George Dangas, David Moliterno, Bernhard Witzenbichler, Annapoorna Kini, Mitchell Krucoff, Jeffrey Bruckel, Antonio Colombo, Alaide Chieffo, Roxana Mehran Icahn School of Medicine at Mount Sinai, New York, New York, United States; Mount Sinai Medical Center, New York, New York, United States; Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, United States; Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States; London School of Hygiene and Tropical Medicine, London, United Kingdom; Cedars Sinai Heart Institute, Los Angeles, California, United States; Groupe Hospitalier Bichat – ClaudeBernard, Paris, France; Mount Sinai Medical Center, New York, New York, United States; University of Kentucky, Lexington, Kentucky, United States; Helios Amper-Klinikum, Dachau, Germany; Unknown, New York, New York, United States; Duke University Medical Center/Duke Clinical Research Institute, Durham, North Carolina, United States; University of Rochester Medical Center; San Raffaele Scientific Institute, Milan, Italy; San Raffaele Scientific Institute, Milan, Italy; Zena and Michael A. Weiner Cardiovascular Institute at Mount Sinai School of Medicine, New York, New York, United States