Search

Importance: Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y12 inhibitor., Objective: To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI., Data Sources: MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction., Study Selection: Included studies were randomized clinical trials comparing P2Y12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI., Data Extraction and Synthesis: Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data., Main Outcomes and Measures: The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding., Results: Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority > .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P < .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P < .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04)., Conclusions and Relevance: This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

Background: Aspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents., Objectives: This study compared P2Y 12 inhibitor monotherapy vs aspirin in patients with CAD., Methods: We conducted a patient-level meta-analysis of randomized trials comparing P2Y 12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis., Results: Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y 12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y 12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y 12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y 12 inhibitors., Conclusions: Given its superior efficacy and similar overall safety, P2Y 12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y 12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774)., Competing Interests: Funding Support and Author Disclosures This study was funded by institutional support of the Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, and the Department of Cardiology at Bern University Hospital, which had no role in the data analysis, interpretation, or writing of the report. There was no industry involvement in the design, analysis, or funding of this study. Dr Valgimigli has received personal fees from AstraZeneca; has received grants and personal fees from Terumo; and has received personal fees from Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals Ltd, Departement Klinische Forschung of Universität Basel, Bristol Myers Squibb SA, Medscape, Biotronik, and Novartis, outside the submitted work. Dr Windecker has received research and educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, Infraredx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohme, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Swiss, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; serves as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave, and Xeltis but has not received personal payments by pharmaceutical companies or device manufacturers; is a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration; is an unpaid member of the Pfizer Research Award selection committee in Switzerland and of the Women as One Awards Committee; is a member of the Clinical Study Group of the Deutsches Zentrum für Herz Kreislauf-Forschung and of the Advisory Board of the Australian Victorian Heart Institute; and is chairperson of the ESC Congress Program Committee and Deputy Editor of JACC: Cardiovascular Interventions. Dr Mehran has served on the scientific advisory boards of the American Medical Association, the American College of Cardiology (Board of Trustees Member), the Society for Cardiovascular Angiography & Interventions (Women in Innovations Committee Member), JAMA Cardiology (Associate Editor), and the Cardiovascular Research Foundation (Faculty) (no fee). Dr Woodward is a consultant for Freeline; and has recently been a consultant to Amgen. Dr Schunkert has received personal fees from Amgen, AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Merck Sharp & Dohme, Novartis, Sanofi, Servier, and SYNLAB. Dr Franzone has received payment or honoraria for lectures, presentations, Speaker Bureaus, manuscript writing, or educational events from Edwards Lifesciences and Boehringer Ingelheim. Dr Bhatt discloses the following relationships—advisory board: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; board of directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; consultant: Broadview Ventures; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the National Institutes of Health–funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART Research and Publications Committee (Chair); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither Dr Bhatt nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (Editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. Dr Steg has received grants, personal fees, and nonfinancial support from Sanofi; has received grants and personal fees from Amarin, Servier, and Bayer; has received personal fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Idorsia, Pfizer, and Novartis; and has a patent on the use of alirocumab to reduce risk after acute coronary syndrome (royalties to Sanofi) pending. Dr Szarek has served as a consultant or on advisory boards (or both) for CiVi, Resverlogix, Baxter, Esperion, Sanofi, and Regeneron Pharmaceuticals, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: It remains unclear whether P2Y 12 inhibitor monotherapy preserves ischemic protection while limiting bleeding risk compared with dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI)., Objectives: We sought to assess the effects of P2Y 12 inhibitor monotherapy after 1-month to 3-month DAPT vs standard DAPT in relation to PCI complexity., Methods: We pooled patient-level data from randomized controlled trials comparing P2Y 12 inhibitor monotherapy and standard DAPT on centrally adjudicated outcomes after coronary revascularization. Complex PCI was defined as any of 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was all-cause mortality, myocardial infarction, and stroke. The key safety endpoint was Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding., Results: Of 22,941 patients undergoing PCI from 5 trials, 4,685 (20.4%) with complex PCI had higher rates of ischemic events. The primary efficacy endpoint was similar between P2Y 12 inhibitor monotherapy and DAPT among patients with complex PCI (HR: 0.87; 95% CI: 0.64-1.19) and noncomplex PCI (HR: 0.91; 95% CI: 0.76-1.09; P interaction  = 0.770). The treatment effect was consistent across all the components of the complex PCI definition. Compared with DAPT, P2Y 12 inhibitor monotherapy consistently reduced BARC 3 or 5 bleeding in complex PCI (HR: 0.51; 95% CI: 0.31-0.84) and noncomplex PCI patients (HR: 0.49; 95% CI: 0.37-0.64; P interaction  = 0.920)., Conclusions: P2Y 12 inhibitor monotherapy after 1-month to 3-month DAPT was associated with similar rates of fatal and ischemic events and lower risk of major bleeding compared with standard DAPT, irrespective of PCI complexity. (PROSPERO [P2Y12 Inhibitor Monotherapy Versus Standard Dual Antiplatelet Therapy After Coronary Revascularization: Individual Patient Data Meta-Analysis of Randomized Trials]; CRD42020176853)., Competing Interests: Funding Support and Author Disclosures This study was funded by institutional support of the Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, which had no role in the data analysis, interpretation, or writing of the report. Dr Mehran has received grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, BMS, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco Inc/dba PLx Pharma Inc, Roivant Sciences, Sanofi, and Medtelligence (Janssen Scientific Affairs); has other financial relationships with Abbott Laboratories, Abiomed, The Medicines Company, Spectranetics/Philips/Volcano Corp, and Watermark Research Partners, outside the submitted work; has received nonfinancial support from Regeneron Pharmaceuticals; and has other relationships with Regeneron Pharmaceuticals and Bristol Myers Squibb. Drs Branca and Heg are affiliated with CTU Bern, University of Bern, which has a staff policy of not accepting honoraria or consultancy fees. However, CTU Bern is involved in design, conduct, or analysis of clinical studies funded by not-for-profit and for-profit organizations such as pharmaceutical and medical device companies provide direct funding to some of these studies. Dr Kimura has received research grants from Abbott Vascular, outside the submitted work. Dr Hahn has received grants or contracts from Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific, outside the submitted work. Dr Windecker has received research, travel, or educational grants to the institution from Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardinal Health, CardioValve, Corflow Therapeutics, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Janssen-Cilag, Johnson & Johnson, Medicure, Medtronic, Merck Sharp & Dohm, Miracor Medical, Novartis, Novo Nordisk, Organon, OrPha Suisse, Pfizer, Polares, Regeneron, Sanofi, Servier, Sinomed, Terumo, Vifor, and V-Wave; serves as unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Boston Scientific, Biotronik, Bristol Myers Squibb, Edwards Lifesciences, Janssen, MedAlliance, Medtronic, Novartis, Polares, Recardio, Sinomed, Terumo, V-Wave and Xeltis; and is a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Gibson has received research or grant funding from CSL Behring, Janssen Pharmaceuticals, Johnson & Johnson Corporation, and SCAD Alliance; has received consulting fees from Amarin, Amag Pharmaceuticals, Angel Medical Corporation, Anthos Therapeutics, AstraZenca, Bayer Corporation Bioclinica, Boston Clinical Research Institute, Boston Scientific, Bristol Myers Squibb, Caladrius Biosciences, Cardiovascular Clinical Science Foundation, Cardiovascular Research Foundation, CeleCor Therapeutics, CSL Behring, CytoSorbents Medical, Inc, Duke Clinical Research Institute, Eidos Therapeutics, EXCITE International, Gilead Sciences, Inc., Inari, Janssen Pharmaceuticals Johnson & Johnson Corporation, MD Magazine, MedImmune, Medtelligence, MedTrace, Merck Microport, Micodrop, LLC, Novo Nordisk, Paratek, PERT Consortium, Pfizer, PhaseBio, PHRI, PLxPharma, Revance Therapeutics, SCAI, Smart Medics, Somahlution, and Web MD; and has received personal fees from UpToDate in Cardiovascular Medicine, and other from Absolutys, nference, and Dyad Medical, outside the submitted work. Dr Watanabe has received honoraria for lectures from Abbott Medical Japan, Daiichi-Sankyo, Pfizer, and Kowa, outside the submitted work. Dr Zhu has received grants from AstraZeneca and Chugaipharma; and has received personal fees from AstraZeneca, Novartis, Sanofi, Medtronic, and Chugaipharma, outside the submitted work; and has received nonfinancial support from Medtronic. Dr Vranckx has received consulting fees or honoraria from Bayer AG, Daiichi-Sankyo, Servier, Bristol Myers Squibb-Pfizer, Menarini, and CSL Behring; has participated data safety monitoring or advisory boards for Novartis; and his institution has received research grants from Daiichi-Sankyo and Medtronic. Dr Serruys has received personal fees from SMT, Philips, Xeltis, Novartis, and Merillife, outside the submitted work. Dr Dangas has received grants from AstraZeneca, during the conduct of the study, Abbott Vascular, Boston Scientific, Medtronic, Daiichi-Sankyo, and Bayer, outside the submitted work; and has received personal fees from Biosensors and Boston Scientific. Dr McFadden has received personal fees from Cardialysis BV, Rotterdam, the Netherlands, outside the submitted work. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation, outside the submitted work. Dr Valgimigli has received grants from Terumo; and has received personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi-Sankyo, Bayer, CoreFlow, Idorsia Pharmaceuticals LTD, Universität Basel, Department. Klinische Forschung, Bristol Myers Squibb SA, Medscape, Biotronik, and Novartis, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P =0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Objectives: We sought to report details of the incidence, organisms, clinical course, and outcomes of prosthetic valve endocarditis (PVE) after transcatheter aortic valve replacement (TAVR) in low-risk patients., Background: PVE remains a rare but devastating complication of aortic valve replacement. Data regarding PVE after TAVR in low-risk patients are lacking., Methods: We performed a detailed review of all patients in the low-risk TAVR trials who underwent TAVR from 2016 to 2020 and were adjudicated to have definitive PVE by the independent Clinical Events Committee., Results: We analyzed 396 low-risk patients who underwent TAVR (including 72 with bicuspid valves). PVE occurred in 11 patients at a median 379 days (210, 528) from TAVR. The incidence within the first 30 days was 0%; days 31-365, 1.5%; and after day 365, 2.8%. The most common organism identified was Streptococcus (n = 4/11). Early PVE (≤ 365 days) occurred in five patients, of whom three demonstrated evidence of embolic stroke and two underwent surgical aortic valve re-intervention. Late PVE (> 365 days) occurred in six patients, of whom thee demonstrated evidence of embolic stroke and only one underwent surgical aortic valve re-intervention. Of the six patients with evidence of embolic stroke, two died, two were discharged to rehabilitation, and two were discharged home with home care., Conclusions: PVE was infrequent following TAVR in low-risk patients but was associated with substantial morbidity and mortality. Embolic stroke complicated the majority of PVE cases, contributing to worse outcomes in these patients. Efforts must be undertaken to minimize PVE in TAVR., (© 2021 Wiley Periodicals LLC.)

Aims: The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints., Methods and Results: The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally adjudicated in GLOBAL LEADERS and GLASSY, respectively. At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 [95% confidence interval (CI): 0.63-0.71] vs. 0.63 (95% CI: 0.59-0.67) in GLOBAL LEADERS (P = 0.27), and 0.67 (95% CI: 0.61-0.73) vs. 0.66 (95% CI: 0.61-0.72) in GLASSY (P = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified four-item PRECISE-DAPT., Conclusion: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: The aim of this study was to investigate the effect of ticagrelor monotherapy after one-month dual antiplatelet therapy (DAPT) or conventional DAPT in patients with or without acute coronary syndrome (ACS) in the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY)., Methods and Results: Risk estimates were expressed as rate ratios (RR) with 95% confidence intervals (CI). A total of 3,840 ACS and 3,745 stable ischaemic heart disease (SIHD) patients were included. At two years, rates of the co-primary efficacy endpoint, a composite of death, myocardial infarction, stroke or urgent target vessel revascularisation, were 7.94% in the experimental and 9.68% in the control group (RR 0.82, 95% CI: 0.66-1.01) among ACS patients and 6.31% in the experimental and 7.14% in the control group (RR 0.89, 95% CI: 0.69-1.13) among SIHD patients (pint=0.63). Trends for lower and higher risk of BARC 3 or 5 bleeding with the experimental strategy in ACS (2.27% vs 3.00%, RR 0.76, 95% CI: 0.51-1.12) and SIHD (2.70% vs 1.96%, RR 1.39, 95% CI: 0.91-2.12) patients, respectively, were observed with significant interaction testing (pint=0.039). A net clinical benefit endpoint, the composite of both co-primary study endpoints, favoured the experimental treatment among ACS patients only., Conclusions: Ticagrelor monotherapy after one-month DAPT provided consistent treatment effects on ischaemic endpoints in patients with or without ACS but only the former experienced a net clinical benefit. ClinicalTrials.gov identifier: NCT03231059.

The definition and clinical implications of myocardial infarction occurring in the setting of percutaneous coronary intervention have been the subject of unresolved controversy. The definitions of periprocedural myocardial infarction (PMI) are many and have evolved over recent years. Additionally, the recent advancement of different imaging modalities has provided useful information on a patients' pre-procedural risk of myocardial infarction. Nonetheless, questions on the benefit of different approaches to prevent PMI and their practical implementation remain open. This review aims to address these questions and to provide a current and contemporary perspective., Competing Interests: Declaration of competing interest Ron Waksman, MD, received honoraria from Abbott Vascular, Amgen, Boston Scientific, Chiesi, Medtronic and Philips Volcano, and consulting fees from Biosensors, Biotronik, Corindus, Lifetech Medical, and Pi-Cardia LTD. He is on the advisory boards of Abbott Vascular, Amgen, Boston Scientific, Medtronic, Philips Volcano, and Pi-Cardia LTD, is a consultant for Abbott Vascular, Amgen, Biosensors, Biotronik, Boston Scientific, Corindus, Lifetech Medical, Medtronic, Philips Volcano, and Pi-Cardia LTD, received grant support from Abbott Vascular, Biosensors, Biotronik, Boston Scientific, Chiesi and Edwards Lifesciences, and is an investor in MedAlliance. All other authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Uncertainty remains regarding the exact prognostic impact of biomarker elevation following percutaneous coronary intervention in patients with stable angina pectoris and the subsequent risk of death. We sought, therefore, to evaluate the effect of periprocedural myocardial infarction on the subsequent mortality risk following percutaneous coronary intervention in patients with stable angina pectoris and normal preprocedural cardiac biomarkers level., Methods: After a systematic literature search was done in PubMed and EMBASE, we performed a meta-analysis of studies with post-procedural cardiac biomarkers data. All-cause mortality and cardiac death were evaluated in subjects with stable angina pectoris who underwent an elective coronary intervention., Results: Fourteen studies with 24 666 patients were included. The mean age was 64.2 years ± 9.8 with about 3-quarters (74.9%) of these patients being men. The mean duration of follow-up was 18.1 months ± 14.3. Periprocedural myocardial infarction, based on study-specific biomarker criteria, occurred in 14.3% of the patients. Periprocedural myocardial infarction conferred a statistically significant increase in the risk of all-cause mortality (odds ratio, 1.62; 95% confidence interval, 1.30-2.01; P < 0.0001; I = 0%); where reported separately, cardiac death was also significantly increase (odds ratio, 2.77; 95% confidence interval, 1.60-4.80; P = 0.0003; I = 0%)., Conclusion: The occurrence of periprocedural myocardial infarction after an elective percutaneous coronary intervention in patients with stable angina pectoris is associated with a statistically significant increase in subsequent all-cause mortality and cardiac mortality.

Objectives: This study sought to explore the association between biomarker elevation, with creatine kinase-myocardial band (CK-MB) or cardiac troponin (cTn), following percutaneous coronary intervention (PCI) and mortality in patients undergoing PCI for stable angina with normal baseline values., Background: Several studies have shown a strong association between post-PCI CK-MB elevation and subsequent mortality. However, the prognostic significance of troponin elevation following coronary intervention is still debated., Methods: Patient-level data from 5 contemporary coronary stent trials and 1 large registry were pooled. Mortality of patients with stable angina, with normal baseline biomarkers, was compared between patients with and those without different cutoff values of cTn and CK-MB., Results: A total of 13,452 patients were included in this pooled analysis. The overall percentage of patients with elevated biomarkers following PCI was 23.9% for CK-MB and 68.4% for cTn. In the patient cohort for whom both assays were available (n = 8,859), 2.4% had both CK-MB ≥5 × the upper limit of normal (ULN) and cTn ≥35 × ULN, while 92% had both CK-MB <5 × ULN and cTn <35 × ULN. Among patients with CK-MB ≥5 × ULN (n = 315), 212 (67.3%) also had cTn ≥35 × ULN. Conversely, 390 of patients (64.8%) who had cTn ≥35 × ULN did not have CK-MB ≥5 × ULN. A total of 259 patients (1.9%) died at 1 year; 20 (7.7%) had CK-MB ≥5 × ULN, and 23 (8.8%) had cTn ≥35 × ULN. In the Cox multivariate analysis, in which the CK-MB and cTn ratios post-procedure were forced into the model, age, prior myocardial infarction, lesion complexity, hyperlipidemia, and CK-MB ratio (≥10) post-procedure were associated with increased 1-year mortality., Conclusions: Following elective PCI in patients in stable condition treated with second-generation drug-eluting stent, CK-MB and cTn elevations remain common. After multivariate adjustment, there was an increased mortality rate with elevation of CK-MB after PCI, whereas cTn elevation was not independently associated with mortality at 1 year., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens., Methods: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed., Findings: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75-1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78-1·20]; p=0·77)., Interpretation: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention., Funding: AstraZeneca, Biosensors, and The Medicines Company., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices., (© 2018 American Heart Association, Inc., and European Society of Cardiology.)

Background: Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients., Methods: Using a double-blind, placebo-controlled, multidose study design, we randomized 47 STEMI patients with significantly reduced (≤40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n = 15), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome., Results: No significant differences in safety end points occurred between treatment groups out to 30 days (χ 2 test, P value = .77). There were no statistically significant differences in baseline (24 hours post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups, with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients, although the result was not statistically significant (P = .095)., Conclusions: In this pilot trial, low-dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose-dependent benefit on post-MI remodeling that may warrant further study., (Copyright © 2018. Published by Elsevier Inc.)

Aims: The purpose of this study was to assess the incidence and predictors of graft failure prior to discharge. Multi-slice computed tomography has the ability to evaluate graft patency in a non-invasive way., Methods and Results: Of 145 consecutive patients who were screened, 73 were included in the study (78% male, mean age 65 years). A total of 206 grafts were analysed (2.8±0.9 grafts/patient). Of the 206 grafts, 126 were venous, 72 were left internal mammary, five were right internal mammary and three were radial grafts. We evaluated 100% of proximal anastomoses sites and 92% (190/206) of the distal anastomoses. We identified five patients (6.8%) who had at least one occluded graft. A total of seven out of 206 (3.4%) grafts were occluded. Independent predictors of successful graft outcome were left anterior descending artery as a recipient artery, good distal run-off as assessed by a surgeon and vessel size larger than 2 mm., Conclusions: The results demonstrate that the in-hospital acute graft failure rate is 3.4% (6.8% of patients). Multi-slice computed tomography is a robust technique to assess novel therapies to reduce the rate of graft attrition further, and might be clinically useful in patients with persistent or early recurrence of symptoms after CABG.

Objectives: This study sought to report the 5-year outcomes of everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) in an all-comers population undergoing percutaneous coronary intervention (PCI)., Background: The medium-term 1 and 2-year results of the prospective randomized COMPARE trial (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice) showed superior clinical outcomes with EES compared with PES in an all-comers PCI population. Whether this benefit is sustained over longer-term follow-up is unknown. Furthermore, systematic long-term follow-up data on these metallic drug eluting stents with durable polymers are scarce., Methods: We randomly assigned 1,800 patients undergoing PCI to EES or PES. The pre-specified composite primary endpoint was death, myocardial infarction (MI), or target vessel revascularization (TVR)., Results: Follow-up at 5 years was completed in 1,791 (99.5%) patients. Treatment with EES compared with PES led to a relative risk reduction of the primary endpoint by 27% (18.4% vs. 25.1%, p = 0.0005), driven by lower rates of MI (7.0% vs. 11.5%, p = 0.001) and TVR (7.4% vs. 11.4%, p = 0.003), but not with mortality (9.0% vs. 10.3%, relative risk 0.88, p = 0.36). Moreover, patients treated with EES compared with PES had lower rates of definite/probable stent thrombosis at 5 years (3.1% vs. 5.9%, p = 0.005). The hazard curves for TVR, MI, and stent thrombosis diverge over the first 3 years and, subsequently, progress in parallel., Conclusions: The early- and medium-term superiority of EES over PES measured both by safety and efficacy endpoints is sustained at 5 years in this all-comer population. (A Trial of Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice [COMPARE]; NCT01016041)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Flash pulmonary edema is characteristically sudden in onset with rapid resolution once appropriate therapy has been instituted (Messerli et al., 2011). Acute increase of left ventricular (LV) end diastolic pressure is the usual cause of sudden decompensated cardiac failure in this patient population. Presence of bilateral renal artery stenosis or unilateral stenosis in combination with a single functional kidney in the susceptible cohort is usually blamed for this condition. We describe a patient who presented with flash pulmonary edema in the setting of normal coronary arteries. Our case is distinct as our patient developed flash pulmonary edema secondary to unilateral renal artery stenosis in the presence of bilateral functioning kidneys. Percutaneous stent implantation in the affected renal artery resulted in rapid resolution of pulmonary edema.

The authors deal with common coronary anomalies, discuss their anatomy and some diagnostic and clinical aspects, and describe some of the principles of management.

Background: Hypoenhanced regions on multidetector CT (MDCT) coronary angiography correlate with myocardial hyperperfusion. In addition to a limited capillary density, chronic myocardial infarction (MI) commonly contains a considerable amount of adipose tissue., Objective: We explored whether regional myocardial hypoenhancement on contrast-enhanced MDCT could be identified with standard coronary artery calcium (CAC) scoring acquisitions with noncontrast CT., Methods: Consecutive patients with a history of MI who were referred for contrast-enhanced MDCT from November 2006 until March 2009 were studied. Noncontrast CT for CAC scoring was also performed. The correlation between regional myocardial hypoenhancement on contrast-enhanced CT and regional myocardial hypoattenuated areas on noncontrast CT was defined., Results: Eighty-three patients (mean age, 61.5+/-12.5 years; n=67; 81% male) with previous MI were studied. A total of 1411 myocardial segments were evaluated. Two hundred thirty-nine segments (17%) showed myocardial hypoenhancement by MDCT and 140 segments (9.6%) by CAC. On a patient level, noncontrast CT showed a sensitivity, specificity, positive predictive value, (PPV) and negative predictive value (NPV) of 66% (95% CI, 0.53-0.77), 100% (95% CI, 0.76-1.00), 100% (95% CI, 0.90-1.00), and 41% (95% CI, 0.26-0.58), respectively, to detect myocardial hypoenhancement. On a per segment level, noncontrast CT showed a sensitivity, specificity, PPV, and NPV of 58% (95% CI, 0.51-0.64), 100% (95% CI, 0.99-1.00), 99% (95% CI, 0.94-1.00), and 92% (95% CI, 0.90-0.93), respectively, to detect myocardial hypoenhancement., Conclusions: Our findings suggest that chronic MI can be detected with standard CAC scoring acquisitions., (Copyright 2010 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

We report a novel percutaneous therapeutic approach to the management of suspected coronary artery steal syndrome resulting from a large side branch of the left internal mammary artery bypass graft, using a combination of coated and drug-eluting stents. We demonstrate the feasibility and long-term efficacy of this strategy in a case report.

Aims: The CAPTIM (Comparison of primary Angioplasty and Pre-hospital fibrinolysis In acute Myocardial infarction) study found no evidence that a strategy of primary angioplasty was superior in terms of 30-day outcomes to a strategy of pre-hospital fibrinolysis with transfer to an interventional facility in patients managed early at the acute phase of an acute myocardial infarction. The present analysis was designed to compare both strategies at 5 years., Methods and Results: The CAPTIM study included 840 patients managed in a pre-hospital setting within 6 h of an acute ST-segment elevation myocardial infarction. Patients were randomized to either a primary angioplasty (n = 421) or a pre-hospital fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities (n = 419). Long-term follow-up was obtained in blinded fashion from 795 patients (94.6%). Using an intent-to-treat analysis, all-cause mortality at 5 years was 9.7% in the pre-hospital fibrinolysis group when compared with 12.6% in the primary angioplasty group [HR 0.75 (95% CI, 0.50-1.14); P = 0.18]. For patients included within 2 h, 5 year mortality was 5.8% in the pre-hospital fibrinolysis group when compared with 11.1% in the primary angioplasty group [HR 0.50 (95% CI, 0.25-0.97); P = 0.04], whereas it was, respectively, 14.5 and 14.4% in patients included after 2 h [HR 1.02, (95% CI 0.59-1.75), P = 0.92]., Conclusion: The 5-year follow-up is consistent with the 30-day outcomes of the trial, showing similar mortality for primary percutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis.

Aims: To determine the adjunctive value of CT coronary angiography (CTCA) in the diagnostic work-up of patients with typical angina pectoris., Methods and Results: CTCA was performed in 62 consecutive patients (45 male, mean age 58.8 +/- 7.7 years) with typical angina undergoing diagnostic work-up including exercise-ECG and conventional coronary angiography. Only patients with sinus heart rhythm and ability to breath hold for 20 s were included. Patients with initial heart rates >/=70 beats/min received beta-blockers. We determined the post-test likelihood ratios, to detect or exclude patients with significant (>/=50% lumen diameter reduction) stenoses, of exercise-ECG and CTCA separately, and of CT performed after exercise-ECG testing. The prevalence of patients with significant coronary artery disease (CAD) was 74%. Positive and negative likelihood ratios for exercise-ECG were 2.3 [95% confidence interval (CI): 1.0-5.3] and 0.3 (95% CI: 0.2-0.7) and for CTCA 7.5 (95% CI: 2.1-27.1) and 0.0 (95% CI: 0.0-8), respectively. CTCA increased the post-test probability of significant CAD after a negative exercise-ECG from 58 to 91%, and after a positive exercise-ECG from 89 to 99%, while CT correctly identified patients without CAD (probability 0%)., Conclusion: Non-invasive CTCA is a potentially useful tool, in the diagnostic work-up of patients with typical angina pectoris, both to detect and to exclude significant CAD.

Background: Surveillance conventional coronary angiography (CCA) is recommended 2 to 6 months after stent-supported left main coronary artery (LMCA) percutaneous coronary intervention due to the unpredictable occurrence of in-stent restenosis (ISR), with its attendant risks. Multislice computed tomography (MSCT) is a promising technique for noninvasive coronary evaluation. We evaluated the diagnostic performance of high-resolution MSCT to detect ISR after stenting of the LMCA., Methods and Results: Seventy-four patients were prospectively identified from a consecutive patient population scheduled for follow-up CCA after LMCA stenting and underwent MSCT before CCA. Until August 2004, a 16-slice scanner was used (n = 27), but we switched to the 64-slice scanner after that period (n = 43). Patients with initial heart rates > 65 bpm received beta-blockers, which resulted in a mean periscan heart rate of 57 +/- 7 bpm. Among patients with technically adequate scans (n = 70), MSCT correctly identified all patients with ISR (10 of 70) but misclassified 5 patients without ISR (false-positives). Overall, the accuracy of MSCT for detection of angiographic ISR was 93%. The sensitivity, specificity, and positive and negative predictive values were 100%, 91%, 67%, and 100%, respectively. When analysis was restricted to patients with stenting of the LMCA with or without extension into a single major side branch, accuracy was 98%. When both branches of the LMCA bifurcation were stented, accuracy was 83%. For the assessment of stent diameter and area, MSCT showed good correlation with intravascular ultrasound (r = 0.78 and 0.73, respectively). An intravascular ultrasound threshold value > or = 1 mm was identified to reliably detect in-stent neointima hyperplasia with MSCT., Conclusions: Current MSCT technology, in combination with optimal heart rate control, allows reliable noninvasive evaluation of selected patients after LMCA stenting. MSCT is safe to exclude left main ISR and may therefore be an acceptable first-line alternative to CCA.

Background: Identification of subclinical high-risk plaques is potentially important because they may have greater likelihood of rupture and subsequent thrombosis. The purpose of this study was to assess the relationship between plaque composition determined by intravascular ultrasound (IVUS) radio frequency (RF) data analysis and clinical presentation., Methods: In 55 patients, a nonculprit vessel with < 50% diameter stenosis was studied with IVUS. Tissue maps were reconstructed from RF data using IVUS-Virtual Histology software., Results: Mean percentage of the different plaque components were 0.99% +/- 0.9%, calcium; 68.04% +/- 9.8%, fibrous; 19.31% +/- 7.3%, fibrolipidic; and 9.43% +/- 6.6%, lipid core. Mean lipid core percentage was significantly larger in patients with acute coronary syndrome (ACS) when compared with stable patients (12.26% +/- 7.0% vs 7.40% +/- 5.5%, P = .006). In addition, stable patients showed more fibrotic vessels (70.97% +/- 9.3% vs 63.96% +/- 9.1%, P = .007). There was no significant difference for either mean calcium (1.20% +/- 1.1% vs 0.83% +/- 0.7%, P = .124) or fibrolipidic (20.57% +/- 6.9% vs 18.40% +/- 7.6%, P = .281) percentages in ACS and stable patients, respectively. Vessel area obstruction did not differ between groups (46.49% +/- 10.9% vs 42.83% +/- 11.8%, P = .221). There was a significant, albeit weak, positive correlation between lipid core percentage and stenosis severity as determined by vessel area obstruction (r = 0.34, P = .015)., Conclusions: In this study, plaque characterization of nonculprit vessels using spectral analysis of IVUS RF data analysis was significantly related to clinical presentation. Percentage of lipid core, a feature related to acute coronary events and worse prognosis, was significantly larger in patients with ACS. Conversely, stable patients showed more fibrotic content.

Objectives: Our purpose was to assess noninvasive imaging in detection of subclinical atherosclerosis and to examine novel invasive modalities to describe prevalence and temporal changes in putative characteristics of "high-risk" plaques., Background: Conventional coronary imaging cannot identify "high-risk" lesions., Methods: Conventional (quantitative angiography and intravascular ultrasound [IVUS]) and novel imaging (IVUS-based palpography and gray scale echogenicity) were performed at baseline and 6 months later in 67 patients with diverse clinical presentations. Different imaging techniques were compared within a common segment defined by multislice computed tomography (MSCT)., Results: Compared with IVUS, the sensitivity, specificity, and positive and negative predictive value of MSCT for detecting significant plaque was 86%, 69%, 90%, and 61%, respectively. In coronary arteries with <50% stenosis, there were no temporal changes in luminal and plaque dimensions measured by quantitative coronary angiography or IVUS; however, a significant reduction in abnormal strain pattern was detected on palpography (density high strain spots/cm: 1.6 +/- 1.5 vs. 1.2 +/- 1.4, p = 0.0123. These changes were mainly related to significant changes in patients who presented with ST-segment elevation myocardial infarction. The assessment of plaque echogenicity showed no temporal changes. There were no correlations between circulating biomarkers and quantifiable imaging parameters., Conclusions: Mild angiographic disease is associated with large atherosclerotic plaques on MSCT. Conventional invasive coronary imaging reveals static luminal and plaque dimensions on standard medical therapy with plaque hypoechogenicity remaining unchanged over the 6-month period. By contrast, palpography measurements of strain correlate with clinical presentation and significantly decrease on standard medical therapy. Novel imaging modalities, such as palpography, might provide insights into plaque biology and might eventually serve as intermediate end points in interventional trials.

Background: We sought to compare, using meta-analytic techniques, bare-metal stent versus balloon angioplasty in the percutaneous treatment of total coronary occlusions by means of a quantitative systematic review and to indicate new avenues for future treatments., Methods: MEDLINE and CENTRAL were searched. Inclusion criteria were random allocation, prospective comparison, and intention to treat. Random-effect odds ratios (ORs) with 95% confidence intervals (CIs) for death, myocardial infarction (MI), repeated revascularization, major adverse cardiac events (MACE), and angiographic restenosis and reocclusion were computed., Results: Nine trials (1409 patients) were included. Death rate was not different in the 2 groups, 0.4% after stenting versus 0.7% after balloon angioplasty (OR 0.72, 95% CI 0.21-2.50). MI rate was significantly increased after stenting (6.7% vs 3.4%, OR 2.06, 95% CI 1.22-3.46), mainly because of a higher rate of periprocedural non-Q-wave MI. By contrast, the risk of repeated revascularization was significantly reduced by stenting (17% vs 32%, OR 0.41, 95% CI 0.31-0.53). This yielded to an overall reduction in the rate of MACE after stenting (23.2% vs 35.4%, OR 0.49, 95% CI 0.36-0.68). Angiographic restenosis and reocclusion were also decreased by stent (41.1% vs 60.9%, OR 0.36, 95% CI 0.23-0.57; 6.8% vs 16%, OR 0.36, 95% CI 0.22-0.59, respectively)., Conclusions: In total coronary occlusions, stenting yields an important benefit over balloon angioplasty in reduction of MACE, repeated revascularizations, and angiographic restenosis and reocclusion. However, these events remain frequent. Moreover, the finding of an increased rate of periprocedural minor myocardial damage after stenting casts caution. New strategies aimed to reduce the need of repeated revascularizations and periprocedural MIs should be further investigated.

Objective: The objective of our study was to compare diagnostic accuracy of MDCT coronary angiography in a population of patients with mild heart rhythm irregularities before and after editing the ECG., Subjects and Methods: Thirty-eight patients who underwent MDCT coronary angiography and conventional coronary angiography were enrolled in the study. The inclusion criterion was the presence of mild heart rhythm irregularities (i.e., premature beats; atrial fibrillation; mistriggering; or low heart rate, defined as 40 beats per minute or less) during the scan. All patients underwent MDCT with the following parameters: 16 detectors; collimation, 0.75 mm; gantry rotation time, 375 msec; 120 kV; and effective milliampere-second setting, 500-600. Images were reconstructed in two settings: before ECG editing and after ECG editing (i.e., arbitrary modification of temporal windows within the cardiac cycle at the site of mild heart rhythm irregularities). Data sets were scored for the presence of significant stenoses (> or = 50% lumen reduction) in coronary segments > or = 2 mm diameter. The results of the two groups were compared with a McNemar test, and a p value of less than 0.05 was considered significant., Results: The sensitivity, specificity, and negative and positive predictive values of MDCT coronary angiography for the detection of significant stenoses before and after ECG editing were 63% (41/65) and 92% (78/85); 97% (251/260) and 96% (305/317); 87% (62/71) and 87% (81/93); 91% (251/275) and 97% (305/313), respectively (p < 0.05). The proportion of nonassessable segments was reduced from 17% (70/416) before ECG editing to 2% (10/416) after., Conclusion: ECG editing significantly improves diagnostic accuracy in a selected population of patients with mild heart rate irregularities.

The objective of this study was to investigate the efficacy of guidewire navigation across coronary artery stenoses using magnetic navigation system (MNS) versus conventional navigation. The MNS is a novel option to facilitate access to target lesions, particularly in tortuous vessels. In an experimental study using a challenging vessel phantom, magnetic-navigated guidewire passage has been reported to reduce fluoroscopy and procedure time significantly. Both magnetic and manual guidewire navigation were attempted in 21 consecutive diseased coronary arteries. The study endpoint was defined as an intraluminal wire position distal to the stenosis. Procedural success was defined as successful guidewire passage without procedural events. Procedure time, amount of contrast, fluoroscopy time, and radiation dose/area product (DAP) were evaluated. There were no procedural events related to either guidewire. Although the lesions attempted had relatively simple and straightforward characteristics, significantly shorter procedure and fluoroscopy time were observed for manual guidewire navigation compared to MNS (median, 40 vs. 120 sec, P=0.001; 38 vs. 105 sec, P=0.001, respectively). Contrast amount and DAP were higher in MNS than in conventional method (median, 13 vs. 9 ml, P=0.018; 215 vs. 73 Gym2, P=0.002, respectively). The magnetic wire did not cross in two vessels. Guidewire navigation using MNS presented a novel, safe, and feasible approach to address coronary artery lesions. Clinical studies are needed to evaluate the potential benefit of the MNS in more complex coronary lesions and tortuous anatomy., (Copyright (c) 2006 Wiley-Liss, Inc.)

Background: Both mechanical and phased-array catheters are used in clinical trials to assess quantitative parameters. Only limited evaluation of the in vivo agreement of volumetrical measurements between such systems has been performed, despite the fact that such information is essential for the conduction of atherosclerosis regression trials., Methods and Results: We prospectively evaluated the agreement in morphometric measurements and intravascular ultrasound (IVUS)-based plaque characterization between a 40 MHz rotating transducer (3.2 F Atlantis, Boston Scientific Corp.) and a 20 MHz phased-array catheter (2.9 F Eagle Eye, Volcano Therapeutics, Rancho Cordova, California) in 16 patients. Lumen (7.3+/-2.0 mm(2) vs. 6.7+/-1.8 mm(2), p=0.001) and vessel (11.8+/-3.3 mm(2) vs. 11.0+/-2.9 mm(2), p=0.02) cross-sectional areas (CSA) were significantly greater with the 20 MHz system. Plaque CSA measurements showed no significant difference between systems (4.4+/-2.3 mm(2) vs. 4.4+/-2.1). The relative differences were less than 10% for the three variables. On IVUS-based tissue characterization (13 patients), calculated percentage hypoechogenic volume was significantly higher for the 20 MHz system (96.7+/-2.38 vs. 88.4+/-5.53, p<0.0001)., Conclusions: Quantitative IVUS analyses display significant catheter type-dependent variability. It is unclear whether the variability reflects overestimation of measurements with the phased-array or underestimation with the mechanical system. Although plaque burden measurements did not differ significantly between systems, it appears prudent to recommend the use of a single system for progression/regression studies.

Aims: Endothelial dysfunction has been related both to progression of atherosclerotic disease and to future cardiovascular events. We assessed local epicardial endothelial function 6 months after sirolimus-eluting stent (SES) or bare metal stent (BS) implantation., Methods and Results: In 12 patients (seven SES, five BS), endothelium-dependent vasomotion of a coronary segment 15 mm in length, starting 2 mm distal to the stent, was assessed with quantitative coronary angiography immediately after the procedure and at 6 months follow-up, after intracoronary infusion of acetylcholine. Intravascular ultrasound (IVUS) was performed and coronary flow reserve (CFR) assessed in all patients. At follow-up significant vasoconstriction was seen in SES (median 32% diameter reduction from baseline) but not in BS (median 2% reduction) patients after acetylcholine infusion (P=0.03 for SES vs. BS); endothelium-independent vasodilatation to nitrates did not differ significantly between groups (20% SES, 5% BS, P=0.14). IVUS revealed no late unhealed dissections and CFR was comparable between groups (SES 3.1 vs. BS 3.2, n.s.)., Conclusion: SES implantation may have an adverse effect on local endothelium-dependent vasomotor responses compared with BS implantation at 6 months. Long-term clinical consequences of this observation are still unknown.

Aims: To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome., Methods and Results: In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04)., Conclusion: Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.

Background: Stented segment length was a predictive factor for restenosis in the bare metal stent era. The objective of the study was to evaluate the medium-term clinical outcome and the potential for adverse effects when very long segments (ie, > or =64 mm of stented length) are treated by drug-eluting stent (DES) implantation, an approach colloquially referred to as a "full metal jacket.", Methods: Since April 2002, we have used DES as the default stent for all percutaneous coronary interventions. From our prospective institutional database we identified 122 consecutive patients, with de novo coronary lesions, in whom a coronary artery was treated with at least 64 mm of overlapping DES: 81 patients were treated with sirolimus-eluting stents and 41 with paclitaxel-eluting stents., Results: The mean number of stents per lesion was 3.3 +/- 1.1, and the median stented length was 79 mm (range 64-168 mm). Periprocedural Q-wave myocardial infarction (MI) occurred in 2 patients (1.6%) and subacute stent thrombosis in 1 patient (0.8%). During 1-year follow-up, 5 patients (4.1%), including 3 patients treated for acute MI with cardiogenic shock, died and 10 patients (8.2%) had nonfatal MI (creatine kinase-MB >3 times). The 1-year target vessel revascularization rate was 7.5% and the overall incidence of major adverse cardiac events was 18%. Outcomes in sirolimus-eluting stents and paclitaxel-eluting stents groups did not differ statistically., Conclusions: The use of DES for the treatment of diffuse lesions was associated with a low rate of repeat revascularization, irrespective of stent type. No safety concerns were raised at medium-term follow-up.

Background: The composition of atherosclerotic coronary plaque is a major determinant of future clinical events. Spectral analysis of IVUS radiofrequency data has demonstrated potential to provide detailed quantitative information on plaque composition. We prospectively assessed plaque composition in matched coronary segments at a six-month interval and sought to explore correlations between temporal changes in plaque composition and circulating biomarkers., Methods and Results: Twenty coronary segments (mean baseline length, 29.9+/-14.1mm) with non-significant angiographic (<50 % diameter) stenosis, in non-culprit vessels of patients (n=20) referred for percutaneous intervention, were studied at baseline and six-month follow-up. Spectral analysis of IVUS radiofrequency data, obtained with a 30 MHz catheter in segments matched on predefined anatomic landmarks, was performed with IVUS-Virtual Histology software. After 6 months, an overall decrease in the level of different biomarkers of instability was present. There were no significant changes in absolute values (mm2) of plaque components; calcium (0.036+/-0.05 vs. 0.033+/-0.04), fibrous (2.68+/-1.5 vs. 2.90+/-1.5), fibrolipidic (0.77+/-0.4 vs. 0.73+/-0.4), and lipid core (0.42+/-0.4 vs. 0.52+/-0.5), between baseline and six-months. Nor did any conventional IVUS variable (lumen, vessel, or plaque cross-sectional area, or percent area stenosis). Change in lipid core area (r=0.51, p=0.024), fibrous area (r=0.49, p=0.033) and calcium area (r=0.63, p=0.004), were significantly correlated with change in Lp-PLA2 activity., Conclusions: Routine medical care does not result in significant overall changes in IVUS-derived plaque size or composition over a 6-month period. This study provides indication of quantifiable boundaries beyond which modifications in tissue composition might be interpreted as statistically significant.

Background: The diagnostic performance of the latest 64-slice CT scanner, with increased temporal (165 ms) and spatial (0.4 mm3) resolution, to detect significant stenoses in the clinically relevant coronary tree is unknown., Methods and Results: We studied 52 patients (34 men; mean age, 59.6+/-12.1 years) with atypical chest pain, stable or unstable angina pectoris, or non-ST-segment elevation myocardial infarction scheduled for diagnostic conventional coronary angiography. All patients had stable sinus rhythm. Patients with initial heart rates > or =70 bpm received beta-blockers. Mean scan time was 13.3+/-0.9 seconds. The CT scans were analyzed by 2 observers unaware of the results of invasive coronary angiography, which was used as the standard of reference. All available coronary segments, regardless of size, were included in the evaluation. Lesions with > or =50 luminal narrowing were considered significant stenoses. Invasive coronary angiography demonstrated the absence of significant disease in 25% (13 of 52), single-vessel disease in 31% (16 of 52), and multivessel disease in 45% (23 of 52) of patients. One unsuccessful CT scan was classified as inconclusive. Ninety-four significant stenoses were present in the remaining 51 patients. Sensitivity, specificity, and positive and negative predictive values of CT for detecting significant stenoses on a segment-by-segment analysis were 99% (93 of 94; 95% CI, 94 to 99), 95% (601 of 631; 95% CI, 93 to 96), 76% (93 of 123; 95% CI, 67 to 89), and 99% (601 of 602; 95% CI, 99 to 100), respectively., Conclusions: Noninvasive 64-slice CT coronary angiography accurately detects coronary stenoses in patients in sinus rhythm and presenting with atypical chest pain, stable or unstable angina, or non-ST-segment elevation myocardial infarction.

Chronic total occlusion (CTO) is one of the most challenging coronary lesions to be faced in the catheterization laboratory. This report of a patient with stable angina and a CTO illustrates the potential problems that may arise and must be overcome, and demonstrates the utilization of technologies including the Intraluminal wire.

Fifty-one patients (42 men; 60 +/- 12 years of age) who had previous stent implantation underwent multislice computed tomographic coronary angiography. All coronary branches > or = 2.0 mm were independently evaluated by 2 observers and screened for in-stent restenosis (> or = 50%) and occlusion. The consensus reading was compared with the quantitative coronary angiogram. Six of the 74 (8.1%) evaluated stents (3 restenoses and 3 occlusions) were significantly diseased. The sensitivity, specificity, and positive and negative predictive values to identify restenosis were 83.3% (95% confidence interval [CI] 35.9 to 99.6), 98.5% (95% CI 92.1 to 100), 83.3% (95% CI 35.9 to 99.6), and 97.3% (95% CI 92.1 to 100), respectively. One in-stent restenosis remained undetected.

Objective: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction., Design and Patients: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period., Setting: Academic tertiary referral centre., Results: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p = 1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p = 0.04). This was driven by stent thrombosis (n = 4), especially in the bifurcation stenting (n = 2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p = 0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p = 0.16)., Conclusions: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.

This study evaluated and compared the efficacy of sirolimus-eluting stents (n = 145 patients) with that of paclitaxel-eluting stents (n = 148 patients) in 293 consecutive unselected patients who had diabetes mellitus. Baseline clinical characteristics and presentations were similar: mean age of 64 years, 50% presented with unstable angina or myocardial infarction, and 66% had multivessel disease. Angiographic and procedural characteristics differed, with more complex lesions and more vein grafts managed in the paclitaxel-eluting stent group. Overall mean stented length was 46 +/- 32 mm. There were no differences in unadjusted outcomes by stent type (1-year major adverse cardiac event rates of 20.4% for sirolimus-eluting stents vs 15.6% for paclitaxel-eluting stents, p = 0.12) or when adjusted for multivariate predictors (adjusted hazard ratio 0.68, 95% confidence interval 0.37 to 1.24, p = 0.21). Independent predictors of outcome in patients who had diabetes mellitus were stenting of the left main artery, stenting of the left anterior descending artery, creatinine clearance, and female gender. Patients who required insulin had a significantly higher, crude major adverse cardiac event rate at 1 year compared with those who used oral agents, but this rate became nonsignificant when adjusted for independent predictors of outcome.

The aim of this study was to evaluate the outcome after paclitaxel-eluting stent implantation in 40 patients with 52 saphenous vein graft lesions. By Kaplan-Meier estimates, the probability of major adverse cardiac event-free survival for 1 year was 92.5%. A paclitaxel-eluting stent for saphenous vein graft disease appears to be feasible and safe, with a low rate of reintervention at 1 year, but late follow-up is needed to confirm these observations.

The institutional review board approved this study, and all patients gave written informed consent. One hundred twenty-five patients scheduled to undergo retrospectively electrocardiographically gated 16-detector row computed tomographic coronary angiography were prospectively randomized into the following five groups with respect to the intravenous administration of a 140-mL bolus of contrast material at 4 mL/sec: group 1 (iohexol [300 mg of iodine per milliliter]), group 2 (iodixanol [320 mg I/mL]), group 3 (iohexol [350 mg I/mL]), group 4 (iomeprol [350 mg I/mL]), and group 5 (iomeprol [400 mg I/mL]). Attenuation was measured in the descending aorta and coronary arteries. One-way analysis of variance was used to compare groups. Mean attenuation values in the descending aorta were significantly (P < .05) lower in group 1 and higher in group 5 compared with the mean values in the other three groups. The same pattern was observed in the coronary arteries. Contrast materials with higher iodine concentrations yield significantly higher attenuation in the descending aorta and coronary arteries.

Aims: Randomized trials of drug-eluting stents (DES) have demonstrated their ability to improve clinical outcome in relatively simple lesion/patient subsets. Their potential in patients for whom the risk of coronary bypass grafting is judged prohibitive, remains largely unexplored. To investigate periprocedural and one-year outcome of percutaneous coronary intervention (PCI) using DES in patients refused for coronary artery bypass grafting (CABG)., Methods and Results: At our institution, the therapeutic approach for all patients with multi-vessel disease is decided, by consensus at a conjoint session with the clinical cardiologist, interventionalist and cardiothoracic surgeon enabling unequivocal identification of patients, refused surgery, who were referred for PCI. The EuroSCORE was used to predict peri-operative mortality. From April 2002 to December 2003 we identified 84 such patients. The mean age was 70.9+/-10.1 years and 68% were men. More than one third had prior CABG. Most patients presented with stable or unstable angina pectoris. The reasons for refusal for CABG were: unsuitable coronary anatomy (37%), poor functional status (28%), patent grafts other than the culprit vessel (25%), prior CABG (28%), severe left ventricular dysfunction (13%), co-existing malignancy (18%), prior disabling stroke (12%) and morbid obesity (11%). Using the standard and logistic EuroSCORE methods, the predicted in-hospital mortality rates were 7.8+/-3.3% and 13.2+/-11.1% respectively. In this study, the actual mortality rate was 1.2% at 30 days, 3.6% at 6 months and 4.8% at 1 year follow-up., Conclusions: PCI in high risk patients who were refused for CABG in the DES-era resulted in an early and 1-year mortality rate that was significantly lower than the predicted operative mortality.

Objectives: We sought to describe the incidence of late angiographic stent thrombosis (LAST) events in an unselected drug-eluting stent (DES) population., Background: Concerns have been raised that LAST may be a potential limitation of DES., Methods: We have previously reported the angiographic incidence of early stent thrombosis (1.0%) in this prospective cohort of 2,006 patients treated with either sirolimus-eluting stents (SES) (n = 1,017) or paclitaxel-eluting stents (PES) (n = 989). We continued long-term follow-up to determine the incidence of LAST events, defined as angiographically proven stent thrombosis associated with acute symptoms more than 30 days after DES implantation. All patients had at least 1 year of follow-up, mean duration 1.5 years., Results: There were eight angiographically confirmed LAST events in seven patients: three with SES (at 2, 25, and 26 months) and five with PES (at 6, 7, 8, 11, and 14.5 months). Three cases were related to complete cessation of antiplatelet therapy, two cases occurred while patients were on aspirin therapy within one month of cessation of clopidogrel, and three cases occurred at a time when patients were apparently clinically stable on aspirin monotherapy. We observed no cases of LAST in patients who were on dual antiplatelet therapy. Two deaths occurred directly as a result of LAST., Conclusions: Angiographically proven late stent thrombosis occurs with an incidence of at least 0.35% (95% confidence limits 0.17% to 0.72%) in patients treated with DES. Importantly, it may also occur when patients are stable on antiplatelet monotherapy.

Objectives: This study was designed to evaluate whether rapid endothelialization of stainless steel stents with a functional endothelium prevents stent thrombosis and reduces the restenotic process., Background: A "pro-healing" approach for prevention of post-stenting restenosis is theoretically favored over the use of cytotoxic or cytostatic local pharmacologic therapies. It is believed that the central role of the vascular endothelium is to maintain quiescence of the underlying media and adventitia., Methods: Sixteen patients with de novo coronary artery disease were successfully treated with implantation of endothelial progenitor cell (EPC) capture stents., Results: Complete procedural and angiographic success was achieved in all 16 patients. The nine-month composite major adverse cardiac and cerebrovascular events (MACCE) rate was 6.3% as a result of a symptom-driven target vessel revascularization in a single patient. There were no other MACCE despite only one month of clopidogrel treatment. At six-month follow-up, mean angiographic late luminal loss was 0.63 +/- 0.52 mm, and percent stent volume obstruction by intravascular ultrasound analysis was 27.2 +/- 20.9%., Conclusions: This first human clinical investigation of this technology demonstrates that the EPC capture coronary stent is safe and feasible for the treatment of de novo coronary artery disease. Further developments in this technology are warranted to evaluate the efficacy of this device for the treatment of coronary artery disease.

We performed coronary plaque imaging with 16-row multislice computed tomography in 85 patients who had stable angina pectoris and a high pretest likelihood of having coronary plaque to evaluate plaque burden, i.e., extent (number of diseased coronary segments) and size (small vs large) of plaque. We also assessed type of plaque (calcified, noncalcified, or mixed) and its anatomic distribution. Of 85 patients included, 78 (92%) had fully evaluable multislice computed tomograms that allowed assessment of coronary plaque burden, including major and side branches (>or=2 mm), yielding a total of 855 segments. These 78 patients (92% men; mean age +/- SD 58 +/- 11.5 years) were in sinus rhythm, with heart rates of <70 beats/min (spontaneous or induced by beta blocker). Plaque was detected in 57% of all segments (487 of 855). The mean number of segments with plaque per patient +/- SD was 6.2 +/- 3.9. Plaque was classified as large in 33% of segments and small in 67%. Overall, 65% of plaques were calcified, 24% were noncalcified, and 11% were mixed. Plaques were predominantly located in the proximal and middle segments of the main coronary vessels.

Context: Bare-metal stenting with abciximab pretreatment is currently considered a reasonable reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for target-vessel revascularization (TVR) vs bare-metal stents but substantially increase procedural costs. At current European list prices, the use of tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs bare-metal stents., Objective: To evaluate the clinical and angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting stenting vs abciximab plus bare-metal stenting in patients with STEMI., Design, Setting, and Patients: Prospective, single-blind, randomized controlled study (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median age, 63 [interquartile range, 55-72] years) presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block and randomized between March 6, 2003, and April 23, 2004., Intervention: Single high-dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard-dose abciximab plus bare-metal stenting (n = 88)., Main Outcome Measures: The primary end point was a composite of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at day 30 and month 8, from major cardiac or cerebrovascular adverse events (composite of death, reinfarction, stroke, and repeat TVR)., Results: Cumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95% CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact test]). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28-0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI, 26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively (P = .002)., Conclusion: Tirofiban-supported sirolimus-eluting stenting of infarcted arteries holds promise for improving outcomes while limiting health care expenditure in patients with myocardial infarction undergoing primary intervention.

Aims: To compare, by meta-analytical techniques, the clinical impact of bare-metal stenting vs. balloon angioplasty for the treatment of lesions in small coronary arteries., Methods and Results: We included trials with random allocation and prospective comparison of angioplasty vs. stenting, reference vessel diameter<3 mm, and follow-up>or=6 months. Random effect odds ratios (OR) for death, myocardial infarction (MI), repeat revascularization (RR), and major adverse cardiac events (MACEs) were computed. In a pre-specified subgroup analysis, we compared stenting with optimal (post-procedural stenosis<20%) and suboptimal (>20%) angioplasty. Thirteen studies (4383 patients) were selected. No differences were found in terms of death and MI, while MACEs, mainly driven by RR, were significantly less common after stenting (17.6%) than after angioplasty (22.7%), OR 0.71 (0.57-0.90). Heterogeneity among trials was present. When considering only optimal angioplasty, MACE rates were homogeneously similar, 17.9 vs. 21.1%, OR 0.86 (0.66-1.11). If angioplasty were suboptimal, MACEs were significantly more common after angioplasty (24%) than after stenting (17.3%), OR 0.62 (0.44-0.88)., Conclusion: Stenting is superior to balloon angioplasty for the treatment of small vessels, in particular after suboptimal angioplasty. However, MACE and RR rates remain high after stenting, and the advantage of stent over angioplasty is moderate. An optimal balloon angioplasty strategy (with provisional stenting) may achieve results not inferior to routine stenting.

Objectives: We investigated the efficacy of paclitaxel-eluting stents (PES) compared to sirolimus-eluting stents (SES) when used without restriction in unselected patients., Background: Both SES and PES have been separately shown to be efficacious when compared to bare stents. In unselected patients, no direct comparison between the two devices has been performed., Methods: Paclitaxel-eluting stents have been used as the stent of choice for all percutaneous coronary interventions in the prospective Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (T-SEARCH) registry. A total of 576 consecutive patients with de novo coronary artery disease exclusively treated with PES were compared with 508 patients treated with SES from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry., Results: The PES patients were more frequently male, more frequently treated for acute myocardial infarction, had longer total stent lengths, and more frequently received glycoprotein IIb/IIIa inhibitors. At one year, the raw cumulative incidence of major adverse cardiac events was 13.9% in the PES group and 10.5% in the SES group (unadjusted hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.95 to 1.88, p = 0.1). Correction for differences in the two groups resulted in an adjusted HR of 1.16 (95% CI 0.81 to 1.64, p = 0.4, using significant univariate variables) and an adjusted HR of 1.20 (95% CI 0.85 to 1.70, p = 0.3, using independent predictors). The one-year cumulative incidence of clinically driven target vessel revascularization was 5.4% versus 3.7%, respectively (HR 1.38, 95% CI 0.79 to 2.43, p = 0.3)., Conclusions: The universal use of PES in an unrestricted setting is safe and is associated with a similar adjusted outcome compared to SES. The inferior trend in crude outcome seen in PES was due to its higher-risk population. A larger, randomized study enrolling an unselected population may assist in determining the relative superiority of either device.