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The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. 49 trials including 50 844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13–0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11–0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08–0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16–0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24–0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10–0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03–0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17–0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19–0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. The Cardiovascular Research Foundation.

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. 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. 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). 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. Abbott Vascular.

Data for the safety and efficacy of new-generation drug-eluting stents at long-term follow-up, and specifically in patients with ST-segment elevation myocardial infarction, are scarce. In the EXAMINATION trial, we compared everolimus-eluting stents (EES) with bare-metal stents (BMS) in an all-comer population with ST-segment elevation myocardial infarction. In this study, we assessed the 5-year outcomes of the population in the EXAMINATION trial. In the multicentre EXAMINATION trial, done in Italy, Spain, and the Netherlands, patients with ST-segment elevation myocardial infarction were randomly assigned in a 1:1 ratio to receive EES or BMS. The random allocation schedule was computer-generated and central randomisation (by telephone) was used to allocate patients in blocks of four or six, stratified by centre. Patients were masked to treatment assignment. At 5 years, we assessed the combined patient-oriented outcome of all-cause death, any myocardial infarction, or any revascularisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00828087. 1498 patients were randomly assigned to receive either EES (n=751) or BMS (n=747). At 5 years, complete clinical follow-up data were obtained for 731 patients treated with EES and 727 treated with BMS (97% of both groups). The patient-oriented endpoint occurred in 159 (21%) patients in the EES group versus 192 (26%) in the BMS group (hazard ratio 0·80, 95% CI 0·65–0·98; p=0·033). This difference was mainly driven by a reduced rate of all-cause mortality (65 [9%] vs 88 [12%]; 0·72, 0·52–0·10; p=0·047). Our findings should be taken as a point of reference for the assessment of new bioresorbable polymer-based metallic stents or bioresorbable scaffolds in patients with ST-segment elevation myocardial infarction. Spanish Heart Foundation.

Physiological assessment of intermediate coronary lesions to guide coronary revascularization is currently recommended by international guidelines. Vessel fractional flow reserve (vFFR) has emerged as a new approach to derive fractional flow reserve (FFR) from 3D-quantitative coronary angiography (3D-QCA) without the need for hyperemic agents or pressure wires. The FAST III is an investigator-initiated, open label, multicenter randomized trial comparing vFFR guided versus FFR guided coronary revascularization in approximately 2228 patients with intermediate coronary lesions (defined as 30%-80% stenosis by visual assessment or QCA). Intermediate lesions are physiologically assessed using on-line vFFR or FFR and treated if vFFR or FFR ≤0.80. The primary end point is a composite of all-cause death, any myocardial infarction, or any revascularization at 1-year post-randomization. Secondary end points include the individual components of the primary end point and cost-effectiveness will be investigated. FAST III is the first randomized trial to explore whether a vFFR guided revascularization strategy is non-inferior to an FFR guided strategy in terms of clinical outcomes at 1-year follow-up in patients with intermediate coronary artery lesions.

The success of therapies targeting myocardial reperfusion injury is limited, while the cardioprotective impact of mitigating ischemia-related damage remains less explored. We have recently shown in a pig model that the intravenous administration of a modified atorvastatin preparation during ischemia attenuates the rise of cardiac ischemia injury biomarkers. In the following study, we sought to investigate the mechanisms behind these ischemia-related cardioprotective effects. Ischemia was induced by 90 min total coronary balloon occlusion in pigs fed a normocholesterolemic regime. Fifteen minutes after the onset of ischemia, animals were randomized to receive intravenous atorvastatin preparation (IV-atorva) or vehicle. After ischemia animals were euthanized to assess the effect of IV-atorva treatment on gene and protein levels/activation of senescence-, apoptosis-, and cardioprotective/metabolic-related markers. Proof-of-concept studies were carried out in mice and rats in which treatments or vehicle were administered 15 min after initiation of ischemia induced by permanent coronary ligation. Western-blot analyses revealed that in the ischemic myocardium of IV-atorva-treated pigs, RhoA was inactivated, phosphorylation of p53 and caspase-3 was reduced and AMPK was activated with the consequent regulation of the mTOR/raptor-signaling pathway. IV-atorva-treated rats showed, as compared to vehicle, a significant reduction (60%) in scar size assessed at 1 month by histological staining, and mice studies demonstrated the causal involvement of AMPK activation in IV-atorva mediated cardioprotective effects. We demonstrate in pigs and rodents that prompt intravenous treatment with atorvastatin during ischemia limits cardiac cell death and reduces infarct size through AMPK signaling.

Platelet Function Profiles in Patients With Type 2 Diabetes and Coronary Artery Disease on Combined Aspirin and Clopidogrel Treatment Dominick J. Angiolillo 1 , Antonio Fernandez-Ortiz 2 , Esther Bernardo 2 , Celia Ramírez 2 , Manel Sabaté 2 , Pilar Jimenez-Quevedo 2 , Rosana Hernández 2 , Raul Moreno 2 , Javier Escaned 2 , Fernando Alfonso 2 , Camino Bañuelos 2 , Marco A. Costa 1 , Theodore A. Bass 1 and Carlos Macaya 2 1 Division of Cardiology, University of Florida, Shands Jacksonville, Jacksonville, Florida 2 Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain Address correspondence and reprint requests to Dominick J. Angiolillo, MD, FACC, FESC, Division of Cardiology, University of Florida, Shands Jacksonville, 655 West 8th St., Jacksonville, FL 32209. E-mail: dominick.angiolillo{at}jax.ufl.edu Abstract To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1 ) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2 ) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic ( n = 16) compared with nondiabetic ( n = 36) patients at baseline and up to 24 h following a 300-mg loading dose ( P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic ( n = 60) compared with nondiabetic ( n = 60) subjects ( P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders ( P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients. CAD, coronary artery disease GP, glycoprotein PRP, platelet-rich plasma Footnotes D.J.A. has received consulting fees from Sanofi-Aventis and Bristol-Myers Squibb. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked \"advertisement\" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted May 13, 2005. Received April 19, 2005. DIABETES

Diffuse coronary artery disease (CAD) impacts the immediate hemodynamic and clinical outcomes of percutaneous coronary intervention (PCI). We evaluated whether the diffuse pattern of CAD derived from angiographic Quantitative flow ratio (QFR) impacts the immediate hemodynamic outcome post-PCI and the medium term predicted vessel-oriented composite endpoint (VOCE). Paired pre-procedure QFRs were assessed in 503 patients and 1022 vessels in the Multivessel TALENT (MVT) trial. The pathophysiological pattern of CAD was defined as “predominantly diffuse” or “focal” according to a virtual QFR pullback pressure gradient (PPG) index < 0.78 and ≥ 0.78, respectively. Physiological “focal severity” was assessed using the QFR gradient per mm (dQFR/ds), with a value ≥ 0.025/mm the threshold for a “major gradient”. A post-PCI QFR ≥ 0.91 was considered optimal. Median pre-PCI PPG index was 0.70 (IQR 0.59–0.80). The prevalence of “predominantly diffuse” CAD and “major gradient” were 68.6% and 85.8%, respectively. A “Predominantly diffuse” pattern with a major gradient had a higher risk of a post-PCI QFR < 0.91 (OR 1.52,95%CI 1.47–1.58). In multivariable analysis, low QFR PPG index (diffuse disease) was an independent determinant of a post-PCI QFR < 0.91 (per 0.1 decrease of QFR PPG index, OR:9.8, 95% CI 3.0–32.2, p < 0.001). Based on post-PCI QFR the predicted 2-year VOCE, a powered endpoint in the MVT trial, was 6.1% and 4.2% in diffuse and focal lesions, respectively. A pre-procedure physiological pattern of diffuse CAD is an independent determinant of an unfavourable immediate hemodynamic outcome post-PCI, and detrimentally affects the predicted 2-year VOCE. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ct2/show/NCT04390672 Unique Identifier: NCT04390672 (registration date 15/05/2020)

Up to 60–70% of patients, undergoing invasive coronary angiography due to angina and demonstrable myocardial ischemia with provocative tests, do not have any obstructive coronary disease. Coronary microvascular angina due to a dysfunction of the coronary microcirculation is the underlying cause in almost 50% of these patients, associated with a bad prognosis and poor quality of life. In recent years, progress has been made in the diagnosis and management of this condition. The aim of this review is to provide an insight into current knowledge of this condition, from current diagnostic methods to the latest treatments.

Thrombocytopenia after transcatheter aortic valve implantation (TAVI) is common and has been related to worse clinical outcomes. Comparison of platelet kinetics among different types of valves is limited. Our objectives were to analyze the differences in drop platelet count (DPC) between balloon-expandable valves (BEVs) and self-expanding valves and their prognostic implications after TAVI. Patients who underwent transfemoral TAVI from 2008 to 2016 were included. Exclusion criteria were severe baseline thrombocytopenia and periprocedural death. Postprocedural platelet counts were collected. Two groups were created: DPC ≤30 and DPC >30%. Valve Academic Research Consortium-2 criteria were used to define outcomes. Study population included 609 patients (age 84.7 ± 6.0, 46.6% males). The mean DPC was 32.5 ± 13.9%. The DPC was higher in the BEV arm (33.9 ± 14.2 vs 30.7 ± 13.4%, p = 0.006), and the nadir was reached later in comparison to the self-expanding valve arm (3.0 ± 1.3 vs 2.5 ± 1.1 days, p <0.001). After multivariable analysis, the use of BEV, known coronary artery disease, and left ventricle ejection fraction were the factors associated with a higher rate of DPC >30%. At 30 days, the DPC >30% was related with a higher rate of life-threatening and/or major bleeding (6.8 vs 2.1%, p = 0.009) and death (3.5 vs 0.8%, p = 0.036). At 1 year, the difference in mortality disappeared. In conclusion, in this cohort of patients, the use of BEV seems to be associated with a higher risk of DPC after TAVI. A DPC ≥30% was related with increased risk of life-threatening and/or major bleeding and death at 30 days. Larger and prospective studies are needed to understand this phenomenon.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with cardiogenic shock despite the lack of evidence from adequately powered randomised clinical trials. Three trials reported so far were underpowered to detect a survival benefit; we therefore conducted an individual patient-based meta-analysis to assess the effect of VA-ECMO on 30-day death rate. Randomised clinical trials comparing early routine use of VA-ECMO versus optimal medical therapy alone in patients presenting with infarct-related cardiogenic shock were identified by searching MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and trial registries until June 12, 2023. Trials were included if at least all-cause death rate 30 days after in-hospital randomisation was reported and trial investigators agreed to collaborate (ie, providing individual patient data). Odds ratios (ORs) as primary outcome measure were pooled using logistic regression models. This study is registered with PROSPERO (CRD42023431258). Four trials (n=567 patients; 284 VA-ECMO, 283 control) were identified and included. Overall, there was no significant reduction of 30-day death rate with the early use of VA-ECMO (OR 0·93; 95% CI 0·66–1·29). Complication rates were higher with VA-ECMO for major bleeding (OR 2·44; 95% CI 1·55–3·84) and peripheral ischaemic vascular complications (OR 3·53; 95% CI 1·70–7·34). Prespecified subgroup analyses were consistent and did not show any benefit for VA-ECMO (pinteraction ≥0·079). VA-ECMO did not reduce 30-day death rate compared with medical therapy alone in patients with infarct-related cardiogenic shock, and an increase in major bleeding and vascular complications was observed. A careful review of the indication for VA-ECMO in this setting is warranted. Foundation Institut für Herzinfarktforschung.