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Coronary Artery Disease: HELP
Articles by Marcus D. Flather
Based on 34 articles published since 2010
(Why 34 articles?)
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Between 2010 and 2020, M. Flather wrote the following 34 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data. 2018

Head, Stuart J / Milojevic, Milan / Daemen, Joost / Ahn, Jung-Min / Boersma, Eric / Christiansen, Evald H / Domanski, Michael J / Farkouh, Michael E / Flather, Marcus / Fuster, Valentin / Hlatky, Mark A / Holm, Niels R / Hueb, Whady A / Kamalesh, Masoor / Kim, Young-Hak / Mäkikallio, Timo / Mohr, Friedrich W / Papageorgiou, Grigorios / Park, Seung-Jung / Rodriguez, Alfredo E / Sabik, Joseph F / Stables, Rodney H / Stone, Gregg W / Serruys, Patrick W / Kappetein, Arie Pieter. ·Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, Netherlands. Electronic address: s.head@erasmusmc.nl. · Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, Netherlands. · Department of Cardiology, Erasmus University Medical Center, Rotterdam, Netherlands. · Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. · Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark. · Icahn School of Medicine at Mount Sinai, New York, NY, USA; Peter Munk Cardiac Centre and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, ON, Canada. · Norwich Medical School University of East Anglia and Norfolk and Norwich University Hospital, Norwich, UK. · Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Stanford University School of Medicine, Stanford, CA, USA. · Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. · Richard L Roudebush VA Medical Center, Indianapolis, IN, USA. · Department of Cardiology, Oulu University Hospital, Oulu, Finland. · Department of Cardiac Surgery, Herzzentrum Universität Leipzig, Leipzig, Germany. · Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Biostatistics, Erasmus University Medical Center, Rotterdam, Netherlands. · Cardiac Unit, Otamendi Hospital, Buenos Aires, Argentina. · Department Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA. · Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital, Liverpool, UK. · Columbia University Medical Center and the Center for Clinical Trials, Cardiovascular Research Foundation, New York, NY, USA. · Imperial College London, London, UK. ·Lancet · Pubmed #29478841.

ABSTRACT: BACKGROUND: Numerous randomised trials have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) for patients with coronary artery disease. However, no studies have been powered to detect a difference in mortality between the revascularisation strategies. METHODS: We did a systematic review up to July 19, 2017, to identify randomised clinical trials comparing CABG with PCI using stents. Eligible studies included patients with multivessel or left main coronary artery disease who did not present with acute myocardial infarction, did PCI with stents (bare-metal or drug-eluting), and had more than 1 year of follow-up for all-cause mortality. In a collaborative, pooled analysis of individual patient data from the identified trials, we estimated all-cause mortality up to 5 years using Kaplan-Meier analyses and compared PCI with CABG using a random-effects Cox proportional-hazards model stratified by trial. Consistency of treatment effect was explored in subgroup analyses, with subgroups defined according to baseline clinical and anatomical characteristics. FINDINGS: We included 11 randomised trials involving 11 518 patients selected by heart teams who were assigned to PCI (n=5753) or to CABG (n=5765). 976 patients died over a mean follow-up of 3·8 years (SD 1·4). Mean Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score was 26·0 (SD 9·5), with 1798 (22·1%) of 8138 patients having a SYNTAX score of 33 or higher. 5 year all-cause mortality was 11·2% after PCI and 9·2% after CABG (hazard ratio [HR] 1·20, 95% CI 1·06-1·37; p=0·0038). 5 year all-cause mortality was significantly different between the interventions in patients with multivessel disease (11·5% after PCI vs 8·9% after CABG; HR 1·28, 95% CI 1·09-1·49; p=0·0019), including in those with diabetes (15·5% vs 10·0%; 1·48, 1·19-1·84; p=0·0004), but not in those without diabetes (8·7% vs 8·0%; 1·08, 0·86-1·36; p=0·49). SYNTAX score had a significant effect on the difference between the interventions in multivessel disease. 5 year all-cause mortality was similar between the interventions in patients with left main disease (10·7% after PCI vs 10·5% after CABG; 1·07, 0·87-1·33; p=0·52), regardless of diabetes status and SYNTAX score. INTERPRETATION: CABG had a mortality benefit over PCI in patients with multivessel disease, particularly those with diabetes and higher coronary complexity. No benefit for CABG over PCI was seen in patients with left main disease. Longer follow-up is needed to better define mortality differences between the revascularisation strategies. FUNDING: None.

2 Clinical Trial B-type natriuretic peptide trumps other prognostic markers in patients assessed for coronary disease. 2019

Kotecha, Dipak / Flather, Marcus D / Atar, Dan / Collins, Peter / Pepper, John / Jenkins, Elizabeth / Reid, Christopher M / Eccleston, David / Anonymous201118. ·Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK. d.kotecha@bham.ac.uk. · Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Melbourne, Australia. d.kotecha@bham.ac.uk. · Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK. · Department of Cardiology, Oslo University Hospital Ulleval, University of Oslo, Oslo, Norway. · Royal Brompton Hospital and National Heart and Lung Institute, Imperial College London, London, UK. · Baker Heart and Diabetes Institute, Melbourne, Australia. · Monash Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Melbourne, Australia. · Faculty of Health Sciences, School of Public Health, Curtin University, Perth, Australia. ·BMC Med · Pubmed #30943979.

ABSTRACT: BACKGROUND: Risk prediction for patients with suspected coronary artery disease is complex due to the common occurrence of prior cardiovascular disease and extensive risk modification in primary care. Numerous markers have the potential to predict prognosis and guide management, but we currently lack robust 'real-world' evidence for their use. METHODS: Prospective, multicentre observational study of consecutive patients referred for elective coronary angiography. Clinicians were blinded to all risk assessments, consisting of conventional factors, radial artery pulse wave analysis, 5-minute heart rate variability, high-sensitivity C-reactive protein and B-type natriuretic peptide (BNP). Blinded, independent adjudication was performed for all-cause mortality and the composite of death, myocardial infarction or stroke, analysed with Cox proportional hazards regression. RESULTS: Five hundred twenty-two patients were assessed with median age 66 years and 21% prior revascularization. Median baseline left ventricular ejection fraction was 64%, and 62% had ≥ 50% stenosis on angiography. During 5.0 years median follow-up, 30% underwent percutaneous and 16% surgical revascularization. In multivariate analysis, only age and BNP were independently associated with outcomes. The adjusted hazard ratio per log unit increase in BNP was 2.15 for mortality (95% CI 1.45-3.19; p = 0.0001) and 1.27 for composite events (1.04-1.54; p = 0.018). Patients with baseline BNP > 100 pg/mL had substantially higher mortality and composite events (20.9% and 32.2%) than those with BNP ≤ 100 pg/mL (5.6% and 15.5%). BNP improved both classification and discrimination of outcomes (p ≤ 0.003), regardless of left ventricular systolic function. Conversely, high-sensitivity C-reactive protein, pulse wave analysis and heart rate variability were unrelated to prognosis at 5 years after risk modification and treatment of coronary disease. CONCLUSIONS: Conventional risk factors and other markers of arterial compliance, inflammation and autonomic function have limited value for prediction of outcomes in risk-modified patients assessed for coronary disease. BNP can independently identify patients with subtle impairment of cardiac function that might benefit from more intensive management. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00403351 Registered on 22 November 2006.

3 Clinical Trial Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin–Coronary Artery Disease Trial. 2011

Wiviott, Stephen D / Flather, Marcus D / O'Donoghue, Michelle L / Goto, Shinya / Fitzgerald, Desmond J / Cura, Fernando / Aylward, Philip / Guetta, Victor / Dudek, Dariusz / Contant, Charles F / Angiolillo, Dominick J / Bhatt, Deepak L / Anonymous3180692. ·Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA. swiviott@partners.org ·Circulation · Pubmed #21502571.

ABSTRACT: BACKGROUND: Thrombin is a key mediator of platelet activation. Atopaxar is a reversible protease-activated receptor-1 antagonist that interferes with thrombin-mediated platelet effects. The phase II Lessons From Antagonizing the Cellular Effect of Thrombin-Coronary Artery Disease (LANCELOT-CAD) trial examined the safety and tolerability of prolonged therapy with atopaxar in subjects with CAD. METHODS AND RESULTS: Subjects with a qualifying history were randomized in a double-blind fashion to 3 dosing regimens of atopaxar (50, 100, or 200 mg daily) or matching placebo for 24 weeks and followed up for an additional 4 weeks. The key safety end points were bleeding according to the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Thrombolysis in Myocardial Infarction (TIMI) classifications. Secondary objectives included platelet aggregation and major adverse cardiac events. Seven hundred and twenty subjects were randomized. Overall bleeding rates tended to be higher with atopaxar compared with placebo by CURE criteria (placebo, 0.6%; atopaxar, 3.9%; relative risk, 6.82, P=0.03; 50 mg, 3.9%; 100 mg, 1.7%; 200 mg, 5.9%; P for trend=0.01) and TIMI criteria (placebo, 6.8%; atopaxar, 10.3%; relative risk, 1.52, P=0.17; 50 mg, 9.9%; 100 mg, 8.1%; 200 mg, 12.9%; P for trend=0.07). There was no difference in major bleeding. Major adverse cardiac events were numerically lower in the atopaxar subjects. All atopaxar regimens achieved high levels of platelet inhibition. A transient elevation in liver transaminases and dose-dependent QTc prolongation without apparent complications were observed in higher-dose atopaxar treatment groups. CONCLUSIONS: In this dose-ranging study of patients with CAD, treatment with atopaxar resulted in platelet inhibition, more minor bleeding, and numerically but not statistically fewer ischemic events. Larger-scale trials are needed to determine whether these patterns translate into clinically meaningful effects. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00312052.

4 Clinical Trial Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease. 2010

Goto, Shinya / Ogawa, Hisao / Takeuchi, Masaru / Flather, Marcus D / Bhatt, Deepak L / Anonymous6520671. ·Department of Medicine (Cardiology), Tokai University School of Medicine, Isehara, Kanagawa 259-1143, Japan. shinichi@is.icc.u-tokai.ac.jp ·Eur Heart J · Pubmed #20805115.

ABSTRACT: AIMS: Two multicentre, randomized, double-blind, placebo-controlled Phase II studies assessed the safety and efficacy of the oral protease-activated receptor 1 (PAR-1) antagonist E5555 in addition to standard therapy in Japanese patients with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD). METHODS AND RESULTS: Patients with ACS (n = 241) or high-risk CAD (n = 263) received E5555 (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients) or 24 weeks (CAD patients). The incidence of TIMI major, minor, and minimal bleeds requiring medical attention was similar in the placebo and combined E5555 (atopaxar) groups (ACS: 6.6% placebo vs. 5.0% E5555; CAD: 1.5% placebo vs. 1.5% E5555). There were no TIMI major bleeds and three CURE major bleeds (two with placebo; one with 100 mg E5555). There was a numerical increase in 'any' TIMI bleeding with the E5555 200 mg dose (ACS: 16.4% placebo vs. 23.0% E5555, P = 0.398; CAD: 4.5% placebo vs. 13.2% E5555, P = 0.081). The rate of major cardiovascular adverse events in the combined E5555 group was not different from placebo (ACS: 6.6% placebo vs. 5.0% E5555, P = 0.73; CAD: 4.5% placebo vs. 1.0% E5555, P = 0.066). There was a statistically significant dose-dependent increase in liver function abnormalities and QTcF with E5555. At trough dosing levels in both populations, mean inhibition of platelet aggregation was > 90% with 100 and 200 mg E5555, and 20-60% with 50 mg E5555. CONCLUSION: E5555 (50, 100, and 200 mg) did not increase clinically significant bleeding, although there was a higher rate of any TIMI bleeding with the highest two doses. All doses tested achieved a significant level of platelet inhibition. There was a significant dose-dependent increase in liver function abnormalities and QTcF. Although further study is needed, PAR-1 antagonism may have the potential to be a novel pathway for platelet inhibition to add on to the current standard of care therapy.

5 Article Disagreement Between Randomized and Observational Evidence on the Use of Bilateral Internal Thoracic Artery Grafting: A Meta-Analytic Approach. 2019

Gaudino, Mario / Rahouma, Mohamed / Hameed, Irbaz / Khan, Faiza M / Taggart, David P / Flather, Marcus / Biondi-Zoccai, Giuseppe / Fremes, Stephen E. ·Department of Cardiothoracic Surgery Weill Cornell Medicine New York City NY. · Nuffield Department of Surgical Sciences University of Oxford United Kingdom. · University of East Anglia Norwich United Kingdom. · Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome Latina Italy. · Mediterranea Cardiocentro Napoli Italy. · Schulich Heart Centre Division of Cardiac Surgery Department of Surgery Sunnybrook Health Sciences Centre University of Toronto Ontario Canada. ·J Am Heart Assoc · Pubmed #31752642.

ABSTRACT: Background The ART (Arterial Revascularization Trial) showed no difference in survival at 10 years between patients assigned to the single versus bilateral internal thoracic artery grafting strategies. This finding is in contrast with the results of most observational studies, where the use of 2 internal thoracic arteries has been associated with improved survival. Methods and Results We selected propensity-matched studies from the most comprehensive observational meta-analysis on the long-term outcomes of patients receiving 1 versus 2 internal thoracic arteries. Individual participant survival data from each study and the ART were reconstructed using an iterative algorithm that was applied to solve the Kaplan-Meier equations. The reconstructed individual participant survival data were aggregated to obtain combined survival curves and Cox regression hazard ratios with 95% CIs. Individual participant survival data were obtained from 14 matched observational studies (24 123 patients) and the ART. The 10-year survival of the control group of ART was significantly higher than that of the matched observational studies (hazard ratio, 0.86; 95% CI, 0.80-0.93). The 10-year survival of the experimental group of ART was significantly lower than that of the bilateral internal thoracic artery group of the observational studies (hazard ratio, 1.11; 95% CI, 1.03-1.20). Conclusions Both the improved outcome of the control arm and the lower beneficial effect of the intervention had played a role in the difference between observational evidence and ART.

6 Article Five-year costs from a randomised comparison of bilateral and single internal thoracic artery grafts. 2019

Little, Matthew / Gray, Alastair / Altman, Doug / Benedetto, Umberto / Flather, Marcus / Gerry, Stephen / Lees, Belinda / Murphy, Jacqueline / Campbell, Helen / Taggart, David. ·Nuffield Department of Population Health, University of Oxford, Oxford, UK. · Nuffield Department of Population Health, University of Oxford Health Economics Research Centre, Oxford, UK. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Centre for Statistics in Medicine, University of Oxford, Oxford, UK. · University of Bristol School of Clinical Science, Bristol, Bristol, UK. · University of East Anglia Faculty of Medicine and Health Sciences, Norwich, Norfolk, UK. · Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, Norfolk, UK. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Centre for Statistics in Medicine, Oxford, UK. · Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, Oxfordshire, UK. ·Heart · Pubmed #30948516.

ABSTRACT: BACKGROUND: The use of bilateral internal thoracic arteries (BITA) for coronary artery bypass grafting (CABG) may improve survival compared with CABG using single internal thoracic arteries (SITA). We assessed the long-term costs of BITA compared with SITA. METHODS: Between June 2004 and December 2007, 3102 patients from 28 hospitals in seven countries were randomised to CABG surgery using BITA (n=1548) or SITA (n=1554). Detailed resource use data were collected from the initial hospital episode and annually up to 5 years. The associated costs of this resource use were assessed from a UK perspective with 5 year totals calculated for each trial arm and pre-selected patient subgroups. RESULTS: Total costs increased by approximately £1000 annually in each arm, with no significant annual difference between trial arms. Cumulative costs per patient at 5-year follow-up remained significantly higher in the BITA group (£18 629) compared with the SITA group (£17 480; mean cost difference £1149, 95% CI £330 to £1968, p=0.006) due to the higher costs of the initial procedure. There were no significant differences between the trial arms in the cost associated with healthcare contacts, medication use or serious adverse events. CONCLUSIONS: Higher index costs for BITA were still present at 5-year follow-up mainly driven by the higher initial cost with no subsequent difference emerging between 1 year and 5 years of follow-up. The overall cost-effectiveness of the two procedures, to be assessed at the primary endpoint of the 10-year follow-up, will depend on composite differences in costs and quality-adjusted survival. TRIAL REGISTRATION NUMBER: ISRCTN46552265.

7 Article Bilateral versus Single Internal-Thoracic-Artery Grafts at 10 Years. 2019

Taggart, David P / Benedetto, Umberto / Gerry, Stephen / Altman, Douglas G / Gray, Alastair M / Lees, Belinda / Gaudino, Mario / Zamvar, Vipin / Bochenek, Andrzej / Buxton, Brian / Choong, Cliff / Clark, Stephen / Deja, Marek / Desai, Jatin / Hasan, Ragheb / Jasinski, Marek / O'Keefe, Peter / Moraes, Fernando / Pepper, John / Seevanayagam, Siven / Sudarshan, Catherine / Trivedi, Uday / Wos, Stanislaw / Puskas, John / Flather, Marcus / Anonymous5130977. ·From the Nuffield Department of Surgical Sciences, John Radcliffe Hospital (D.P.T., B.L.), the Centre for Statistics in Medicine, Botnar Research Centre (S.G., D.G.A.), and the Health Economics Research Centre, Nuffield Department of Population Health (A.M.G.), University of Oxford, Oxford, the School of Clinical Sciences, University of Bristol, and Bristol Royal Infirmary, Bristol (U.B.), the Department of Cardiac Surgery, Royal Infirmary of Edinburgh, Edinburgh (V.Z.), Royal Papworth Hospital, Cambridge (C.C., C.S.), the Department of Cardiac Surgery, Freeman Hospital, Newcastle (S.C.), the Department of Cardiac Surgery, King's College Hospital (J.D.), and Royal Brompton Hospital and Imperial College London (J. Pepper), London, the Department of Cardiac Surgery, Royal Infirmary, Manchester (R.H.), the Department of Cardiac Surgery, University Hospital of Wales, Cardiff (P.O.), the Department of Cardiac Surgery, Royal Sussex County, Brighton (U.T.), and Norwich Medical School, University of East Anglia, and Norfolk and Norwich University Hospital, Norwich (M.F.) - all in the United Kingdom · the Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York Presbyterian Hospital (M.G.), and Mount Sinai St. Luke's (J. Puskas) - both in New York · the Center for Cardiovascular Research and Development, American Heart of Poland (A.B.), and the Department of Cardiac Surgery, Medical University of Silesia (M.D., S.W.), Katowice, and the Department of Cardiac and Thoracic Surgery, Wroclaw Medical University, Wroclaw (M.J.) - all in Poland · the Department of Cardiac Surgery, Austin Health, Melbourne, VIC, Australia (B.B., S.S.) · and the Heart Institute of Pernambuco, Recife, Brazil (F.M.). ·N Engl J Med · Pubmed #30699314.

ABSTRACT: BACKGROUND: Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG. METHODS: We randomly assigned patients scheduled for CABG to undergo bilateral or single internal-thoracic-artery grafting. Additional arterial or vein grafts were used as indicated. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. RESULTS: A total of 1548 patients were randomly assigned to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group) and 1554 to undergo single internal-thoracic-artery grafting (the single-graft group). In the bilateral-graft group, 13.9% of the patients received only a single internal-thoracic-artery graft, and in the single-graft group, 21.8% of the patients also received a radial-artery graft. Vital status was not known for 2.3% of the patients at 10 years. In the intention-to-treat analysis at 10 years, there were 315 deaths (20.3% of the patients) in the bilateral-graft group and 329 deaths (21.2%) in the single-graft group (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.12; P=0.62). Regarding the composite outcome of death, myocardial infarction, or stroke, there were 385 patients (24.9%) with an event in the bilateral-graft group and 425 patients (27.3%) with an event in the single-graft group (hazard ratio, 0.90; 95% CI, 0.79 to 1.03). CONCLUSIONS: Among patients who were scheduled for CABG and had been randomly assigned to undergo bilateral or single internal-thoracic-artery grafting, there was no significant between-group difference in the rate of death from any cause at 10 years in the intention-to-treat analysis. Further studies are needed to determine whether multiple arterial grafts provide better outcomes than a single internal-thoracic-artery graft. (Funded by the British Heath Foundation and others; Current Controlled Trials number, ISRCTN46552265 .).

8 Article Stroke Rates Following Surgical Versus Percutaneous Coronary Revascularization. 2018

Head, Stuart J / Milojevic, Milan / Daemen, Joost / Ahn, Jung-Min / Boersma, Eric / Christiansen, Evald H / Domanski, Michael J / Farkouh, Michael E / Flather, Marcus / Fuster, Valentin / Hlatky, Mark A / Holm, Niels R / Hueb, Whady A / Kamalesh, Masoor / Kim, Young-Hak / Mäkikallio, Timo / Mohr, Friedrich W / Papageorgiou, Grigorios / Park, Seung-Jung / Rodriguez, Alfredo E / Sabik, Joseph F / Stables, Rodney H / Stone, Gregg W / Serruys, Patrick W / Kappetein, A Pieter. ·Department of Cardiothoracic Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: s.head@erasmusmc.nl. · Department of Cardiothoracic Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Cardiology, Erasmus Medical College, Rotterdam, the Netherlands. · Department of Cardiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. · Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark. · Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Cardiology, Peter Munk Cardiac Centre and Department of Medicine, Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada. · Department of Medicine and Health Sciences, Norwich Medical School University of East Anglia and Norfolk and Norwich University Hospital, Norwich, United Kingdom. · Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. · Department of Health Research and Policy, and Department of Medicine (Cardiovascular Medicine), Stanford University School of Medicine, Stanford, California. · Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil. · Department of Cardiology, Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana. · Department of Cardiology, Oulu University Hospital, Oulu, Finland. · Department of Cardiac Surgery, Herzzentrum Universität Leipzig, Leipzig, Germany. · Department of Cardiothoracic Surgery, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands. · Cardiac Unit, Otamendi Hospital, Buenos Aires, Argentina. · Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio. · Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. · Department of Cardiology, Columbia University Medical Center and Clinical Trials Center, the Cardiovascular Research Foundation, New York, New York. · Department of Cardiology, Imperial College London, London, United Kingdom. ·J Am Coll Cardiol · Pubmed #30025574.

ABSTRACT: BACKGROUND: Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are used for coronary revascularization in patients with multivessel and left main coronary artery disease. Stroke is among the most feared complications of revascularization. Due to its infrequency, studies with large numbers of patients are required to detect differences in stroke rates between CABG and PCI. OBJECTIVES: This study sought to compare rates of stroke after CABG and PCI and the impact of procedural stroke on long-term mortality. METHODS: We performed a collaborative individual patient-data pooled analysis of 11 randomized clinical trials comparing CABG with PCI using stents; ERACI II (Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease) (n = 450), ARTS (Arterial Revascularization Therapy Study) (n = 1,205), MASS II (Medicine, Angioplasty, or Surgery Study) (n = 408), SoS (Stent or Surgery) trial (n = 988), SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial (n = 1,800), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease) trial (n = 600), FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes) trial (n = 1,900), VA CARDS (Coronary Artery Revascularization in Diabetes) (n = 198), BEST (Bypass Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary Artery Disease) (n = 880), NOBLE (Percutaneous Coronary Angioplasty Versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis) trial (n = 1,184), and EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial (n = 1,905). The 30-day and 5-year stroke rates were compared between CABG and PCI using a random effects Cox proportional hazards model, stratified by trial. The impact of stroke on 5-year mortality was explored. RESULTS: The analysis included 11,518 patients randomly assigned to PCI (n = 5,753) or CABG (n = 5,765) with a mean follow-up of 3.8 ± 1.4 years during which a total of 293 strokes occurred. At 30 days, the rate of stroke was 0.4% after PCI and 1.1% after CABG (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.20 to 0.53; p < 0.001). At 5-year follow-up, stroke remained significantly lower after PCI than after CABG (2.6% vs. 3.2%; HR: 0.77; 95% CI: 0.61 to 0.97; p = 0.027). Rates of stroke between 31 days and 5 years were comparable: 2.2% after PCI versus 2.1% after CABG (HR: 1.05; 95% CI: 0.80 to 1.38; p = 0.72). No significant interactions between treatment and baseline clinical or angiographic variables for the 5-year rate of stroke were present, except for diabetic patients (PCI: 2.6% vs. CABG: 4.9%) and nondiabetic patients (PCI: 2.6% vs. CABG: 2.4%) (p for interaction = 0.004). Patients who experienced a stroke within 30 days of the procedure had significantly higher 5-year mortality versus those without a stroke, both after PCI (45.7% vs. 11.1%, p < 0.001) and CABG (41.5% vs. 8.9%, p < 0.001). CONCLUSIONS: This individual patient-data pooled analysis demonstrates that 5-year stroke rates are significantly lower after PCI compared with CABG, driven by a reduced risk of stroke in the 30-day post-procedural period but a similar risk of stroke between 31 days and 5 years. The greater risk of stroke after CABG compared with PCI was confined to patients with multivessel disease and diabetes. Five-year mortality was markedly higher for patients experiencing a stroke within 30 days after revascularization.

9 Article Incidence and clinical implications of intraoperative bilateral internal thoracic artery graft conversion: Insights from the Arterial Revascularization Trial. 2018

Benedetto, Umberto / Altman, Douglas G / Flather, Marcus / Gerry, Stephen / Gray, Alastair / Lees, Belinda / Taggart, David P / Anonymous4690940. ·Bristol Heart Institute, University of Bristol, School of Clinical Sciences, United Kingdom. Electronic address: Umberto.benedetto@bristol.ac.uk. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. · Norwich Medical School, University of East Anglia and Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom. · Nuffield Department of Population Health, Health Economics Research Centre, University of Oxford, Oxford, United Kingdom. · Bristol Heart Institute, University of Bristol, School of Clinical Sciences, United Kingdom. · Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. ·J Thorac Cardiovasc Surg · Pubmed #29559261.

ABSTRACT: BACKGROUND: The Arterial Revascularization Trial has been designed to answer the question whether the use of bilateral internal thoracic arteries can improve 10-year outcomes when compared with single internal thoracic arteries. In the Arterial Revascularization Trial, a significant proportion of patients initially allocated to bilateral internal thoracic arteries received other conduit strategies. We sought to investigate the incidence and clinical implication of bilateral internal thoracic artery graft conversion in the Arterial Revascularization Trial. METHODS: Among patients enrolled in the Arterial Revascularization Trial (n = 3102), we excluded those allocated to single internal thoracic arteries (n = 1554), those who did not undergo surgery (n = 16), and those who underwent operation but withdrew after randomization (n = 7). Propensity score matching was used to compare converted versus nonconverted bilateral internal thoracic artery groups. RESULTS: A total of 1525 patients were operated with the intention to receive bilateral internal thoracic artery grafting. Of those, 233 (15.3%) were converted to other conduit selection strategies. Incidence of conversion largely varied across 131 participating surgeons (from 0% to 100%). The most common reason for bilateral internal thoracic artery graft conversion was the evidence of at least 1 internal thoracic artery that was not suitable, which was reported in 77 cases. Patients with intraoperative bilateral internal thoracic artery graft conversion received a lower number of grafts (2.95 ± 0.84 vs 3.21 ± 0.74; P < .001). However, the hospital mortality rate was comparable to that of those who did not require bilateral internal thoracic artery graft conversion (0% vs 1.6%; P = .1), as well as the incidence of major complications. At 5 years, we found a nonsignificant excess of deaths (11.9% vs 8.4%; P = .1) and major adverse events (17.1% 13.2%; P = .1) mainly driven by an excess of revascularization in patients requiring conversion. CONCLUSIONS: The incidence of intraoperative bilateral internal thoracic artery graft conversion is not infrequent. Bilateral internal thoracic artery graft conversion is not associated with increased operative morbidity, but its effect on late outcomes remains uncertain.

10 Article Safety of Perioperative Aprotinin Administration During Isolated Coronary Artery Bypass Graft Surgery: Insights From the ART (Arterial Revascularization Trial). 2018

Benedetto, Umberto / Altman, Douglas G / Gerry, Stephen / Gray, Alastair / Lees, Belinda / Angelini, Gianni D / Flather, Marcus / Taggart, David P / Anonymous1811133. ·Bristol Heart Institute, School of Clinical Sciences, University of Bristol, United Kingdom umberto.benedetto@bristol.ac.uk. · Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Centre for Statistics in Medicine, University of Oxford, United Kingdom. · Nuffield Department of Population Health, Health Economics Research Centre, University of Oxford, United Kingdom. · Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, United Kingdom. · Bristol Heart Institute, School of Clinical Sciences, University of Bristol, United Kingdom. · Norwich Medical School, University of East Anglia, Norwich, United Kingdom. · Norfolk and Norwich University Hospitals National Health Service Foundation Trust, Norwich, United Kingdom. ·J Am Heart Assoc · Pubmed #29502105.

ABSTRACT: BACKGROUND: There is still uncertainty about the safety of aprotinin for coronary artery bypass graft surgery. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral versus single internal thoracic artery grafting. Many of the ART patients (≈30%) received perioperative aprotinin. We investigated the association between perioperative aprotinin administration and short-term (in-hospital) and long-term outcomes by performing a post hoc analysis of the ART. METHODS AND RESULTS: Among patients enrolled in the ART (n=3102) from 2004 to 2007, we excluded those who did not undergo surgery (n=18) and those with no information about use of perioperative aprotinin (n=9). Finally, 836 of 3076 patients (27%) received aprotinin. Propensity matching was used to select 536 pairs for final comparison. Aprotinin was also associated with an increased risk of hospital mortality (9 [1.7%] versus 1 [0.2%]; odds ratio, 9.12; 95% confidence interval [CI], 1.15-72.2; CONCLUSIONS: In the present post hoc ART analysis, aprotinin was associated with a significantly increased risk of early and late mortality. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN46552265.

11 Article High-Sensitivity Cardiac Troponin I and the Diagnosis of Coronary Artery Disease in Patients With Suspected Angina Pectoris. 2018

Adamson, Philip D / Hunter, Amanda / Madsen, Debbie M / Shah, Anoop S V / McAllister, David A / Pawade, Tania A / Williams, Michelle C / Berry, Colin / Boon, Nicholas A / Flather, Marcus / Forbes, John / McLean, Scott / Roditi, Giles / Timmis, Adam D / van Beek, Edwin J R / Dweck, Marc R / Mickley, Hans / Mills, Nicholas L / Newby, David E. ·From the British Heart Foundation Centre for Cardiovascular Science (P.D.A., A.H., A.S.V.S., T.A.P., N.A.B., E.J.R.v.B., M.R.D., N.L.M., D.E.N.) and Clinical Research Imaging Centre (M.C.W.), University of Edinburgh, United Kingdom · Department of Cardiology, Odense University Hospital, Denmark (D.M.M., H.M.) · Institute of Health and Wellbeing (D.A.M.) and Institute of Clinical Sciences (C.B., G.R.), University of Glasgow, United Kingdom · Norwich Medical School, University of East Anglia, Norwich, United Kingdom (M.F.) · Health Research Institute, University of Limerick, Ireland (J.F.) · National Health Service, Fife, United Kingdom (S.M.) · and William Harvey Research Institute, Queen Mary University of London, United Kingdom (A.D.T.). ·Circ Cardiovasc Qual Outcomes · Pubmed #29444926.

ABSTRACT: BACKGROUND: We determined whether high-sensitivity cardiac troponin I can improve the estimation of the pretest probability for obstructive coronary artery disease (CAD) in patients with suspected stable angina. METHODS AND RESULTS: In a prespecified substudy of the SCOT-HEART trial (Scottish Computed Tomography of the Heart), plasma cardiac troponin was measured using a high-sensitivity single-molecule counting assay in 943 adults with suspected stable angina who had undergone coronary computed tomographic angiography. Rates of obstructive CAD were compared with the pretest probability determined by the CAD Consortium risk model with and without cardiac troponin concentrations. External validation was undertaken in an independent study population from Denmark comprising 487 patients with suspected stable angina. Higher cardiac troponin concentrations were associated with obstructive CAD with a 5-fold increase across quintiles (9%-48%; CONCLUSIONS: High-sensitivity cardiac troponin I concentration is an independent predictor of obstructive CAD in patients with suspected stable angina. Use of this test may improve the selection of patients for further investigation and treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01149590.

12 Article Off-pump versus on-pump coronary artery bypass grafting: Insights from the Arterial Revascularization Trial. 2018

Benedetto, Umberto / Altman, Douglas G / Gerry, Stephen / Gray, Alastair / Lees, Belinda / Flather, Marcus / Taggart, David P / Anonymous2700934. ·Bristol Heart Institute, University of Bristol, School of Clinical Sciences, Bristol, United Kingdom. Electronic address: Umberto.benedetto@hotmail.com. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. · Department of Public Health, Health Economics Research Centre, University of Oxford, Oxford, United Kingdom. · Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. · Research and Development Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom. ·J Thorac Cardiovasc Surg · Pubmed #29366570.

ABSTRACT: BACKGROUND: The long-term effects of off-pump coronary artery bypass continue to be controversial because some studies have reported increased adverse event rates with off-pump coronary artery bypass when compared with on-pump coronary artery bypass. The Arterial Revascularization Trial compared survival after bilateral versus single internal thoracic artery grafting. The choice of off-pump coronary artery bypass versus on-pump coronary artery bypass was based on the surgeon's discretion. We performed a post hoc analysis of the Arterial Revascularization Trial to compare 5-year outcomes with 2 strategies. METHODS: Among 3102 patients enrolled in the Arterial Revascularization Trial, we selected 1260 patients who underwent off-pump coronary artery bypass versus 1700 patients who underwent on-pump coronary artery bypass with cardioplegic arrest for the present comparison. Primary outcomes were 5-year mortality and incidence of major cardiac and cerebrovascular events, including cardiovascular death, myocardial infarction, cerebrovascular accident, and revascularization after index procedure. Propensity score matching selected 1260 pairs for final comparison. Stratified Cox models were used for treatment effect estimate. RESULTS: Hospital mortality was comparable between off-pump coronary artery bypass and on-pump coronary artery bypass groups (12 [1.0%] vs 15 [1.2%]; P = .7). Conversion rate to on-pump during off-pump coronary artery bypass was 29 of 1260 (2.3%). When compared with off-pump coronary artery bypass not converted, off-pump coronary artery bypass converted to on-pump presented a remarkably higher hospital mortality (10.3% vs 0.7%; P < .001). At 5 years, the mortality rate was 110 (8.9%) versus 102 (8.3%) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.14; 95% confidence interval, 0.86-1.52; P = .35). Incidence of major cardiac and cerebrovascular events was 175 (14.3) versus 169 (13.8) in the off-pump coronary artery bypass and on-pump coronary artery bypass groups, respectively, with no significant difference (hazard ratio, 1.05; 95% confidence interval, 0.84-1.31; P = .65). CONCLUSIONS: The present post hoc Arterial Revascularization Trial analysis supports the hypothesis that both off-pump coronary artery bypass and on-pump coronary artery bypass are equally effective and safe.

13 Article Diagnostic and prognostic benefits of computed tomography coronary angiography using the 2016 National Institute for Health and Care Excellence guidance within a randomised trial. 2018

Adamson, Philip D / Hunter, Amanda / Williams, Michelle C / Shah, Anoop S V / McAllister, David A / Pawade, Tania A / Dweck, Marc R / Mills, Nicholas L / Berry, Colin / Boon, Nicholas A / Clark, Elizabeth / Flather, Marcus / Forbes, John / McLean, Scott / Roditi, Giles / van Beek, Edwin J R / Timmis, Adam D / Newby, David E. ·BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. · Edinburgh Imaging, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK. · Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK. · Institute of Clinical Sciences, University of Glasgow, Glasgow, UK. · Norwich Medical School, University of East Anglia, Norwich, UK. · Health Research Institute, University of Limerick, Limerick, Ireland. · National Health Service, Fife, UK. · William Harvey Research Institute, Queen Mary University of London, London, UK. ·Heart · Pubmed #28844992.

ABSTRACT: OBJECTIVES: To evaluate the diagnostic and prognostic benefits of CT coronary angiography (CTCA) using the 2016 National Institute for Health and Care Excellence (NICE) guidelines for the assessment of suspected stable angina. METHODS: Post hoc analysis of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial of 4146 participants with suspected angina randomised to CTCA. Patients were dichotomised into NICE guideline-defined possible angina and non-anginal presentations. Primary (diagnostic) endpoint was diagnostic certainty of angina at 6 weeks and prognostic endpoint comprised fatal and non-fatal myocardial infarction (MI). RESULTS: In 3770 eligible participants, CTCA increased diagnostic certainty more in those with possible angina (relative risk (RR) 2.22 (95% CI 1.91 to 2.60), p<0.001) than those with non-anginal symptoms (RR 1.30 (1.11 to 1.53), p=0.002; p CONCLUSIONS: NICE-guided patient selection maximises the benefits of CTCA on diagnostic certainty, use of invasive coronary angiography and reductions in fatal and non-fatal myocardial infarction. Patients with non-anginal chest pain derive minimal benefit from CTCA and increase the rates of invasive investigation. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01149590;post results.

14 Article Economic Evaluation of Complete Revascularization for Patients with Multivessel Disease Undergoing Primary Percutaneous Coronary Intervention. 2017

Barton, Garry R / Irvine, Lisa / Flather, Marcus / McCann, Gerry P / Curzen, Nick / Gershlick, Anthony H / Anonymous10711124. ·Norwich Medical School, University of East Anglia, Norwich, UK. Electronic address: g.barton@uea.ac.uk. · Norwich Medical School, University of East Anglia, Norwich, UK. · Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; NIHR Leicester Cardiovascular Biomedical Research Unit, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK. · University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine, University of Southampton, Southampton, UK. ·Value Health · Pubmed #28577691.

ABSTRACT: OBJECTIVES: To determine the cost-effectiveness of complete revascularization at index admission compared with infarct-related artery (IRA) treatment only, in patients with multivessel disease undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction. METHODS: An economic evaluation of a multicenter randomized trial was conducted, comparing complete revascularization at index admission to IRA-only P-PCI in patients with multivessel disease (12-month follow-up). Overall hospital costs (costs for P-PCI procedure(s), hospital length of stay, and any subsequent re-admissions) were estimated. Outcomes were major adverse cardiac events (MACEs, a composite of all-cause death, recurrent myocardial infarction, heart failure, and ischemia-driven revascularization) and quality-adjusted life-years (QALYs) derived from the three-level EuroQol five-dimensional questionnaire. Multiple imputation was undertaken. The mean incremental cost and effect, with associated 95% confidence intervals, the incremental cost-effectiveness ratio, and the cost-effectiveness acceptability curve were estimated. RESULTS: On the basis of 296 patients, the mean incremental overall hospital cost for complete revascularization was estimated to be -£215.96 (-£1390.20 to £958.29), compared with IRA-only, with a per-patient mean reduction in MACEs of 0.170 (0.044 to 0.296) and a QALY gain of 0.011 (-0.019 to 0.041). According to the cost-effectiveness acceptability curve, the probability of complete revascularization being cost-effective was estimated to be 72.0% at a willingness-to-pay threshold value of £20,000 per QALY. CONCLUSIONS: Complete revascularization at index admission was estimated to be more effective (in terms of MACEs and QALYs) and cost-effective (overall costs were estimated to be lower and complete revascularization thereby dominated IRA-only). There was, however, some uncertainty associated with this decision.

15 Article Associations Between Adding a Radial Artery Graft to Single and Bilateral Internal Thoracic Artery Grafts and Outcomes: Insights From the Arterial Revascularization Trial. 2017

Taggart, David P / Altman, Douglas G / Flather, Marcus / Gerry, Stephen / Gray, Alastair / Lees, Belinda / Benedetto, Umberto / Anonymous2520908. ·From Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, United Kingdom (D.P.T., B.L.) · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (D.G.A., S.G.), and Department of Public Health, Health Economics Research Centre (A.G.), University of Oxford, United Kingdom · Norwich Medical School, University of East Anglia, and Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom (M.F.) · and Bristol Heart Institute, School of Clinical Sciences, University of Bristol, United Kingdom (U.B.). ·Circulation · Pubmed #28566338.

ABSTRACT: BACKGROUND: Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft surgery remains unclear. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (≈20%) also received an RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of an SVG to supplement SITA or BITA grafts and outcomes by performing a post hoc analysis of the ART. METHODS: Patients enrolled in the ART (n=3102) were classified on the basis of conduits actually received (as treated). The analysis included 2737 patients who received an RA graft (RA group; n=632) or SVG only (SVG group; n=2105) in addition to SITA or BITA grafts. The primary end point was the composite of myocardial infarction, cardiovascular death, and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the 2 strategies. RESULTS: Myocardial infarction, cardiovascular death, and repeat revascularization cumulative incidence was 2.3% (95% confidence interval [CI], 1.1-3.4), 3.5% (95% CI, 2.1-5.0), and 4.4% (95% CI, 2.8-6.0) in the RA group and 3.4% (95% CI, 2.0-4.8), 4.0% (95% CI, 2.5-5.6), and 7.6% (95% CI, 5.5-9.7) in the SVG group, respectively. The composite end point was significantly lower in the RA group (8.8%; 95% CI, 6.5-11.0) compared with the SVG group (13.6%; 95% CI, 10.8-16.3; CONCLUSIONS: This post hoc ART analysis showed that an additional RA was associated with lower risk for midterm major adverse cardiac events when used to supplement SITA or BITA grafts. CLINICAL TRIAL REGISTRATION: URL: https://www.situ.ox.ac.uk/surgical-trials/art. Unique identifier: ISRCTN46552265.

16 Article Inflammatory Differences in Plaque Erosion and Rupture in Patients With ST-Segment Elevation Myocardial Infarction. 2017

Chandran, Sujay / Watkins, Johnathan / Abdul-Aziz, Amina / Shafat, Manar / Calvert, Patrick A / Bowles, Kristian M / Flather, Marcus D / Rushworth, Stuart A / Ryding, Alisdair D. ·Norfolk and Norwich University Hospital, Norwich, United Kingdom. · Norwich Medical School, University of East Anglia, Norwich, United Kingdom. · PILAR Research and Education, Cambridge, United Kingdom. · Papworth Hospital NHS Foundation Trust, Papworth Everard Cambridge, United Kingdom. · Norfolk and Norwich University Hospital, Norwich, United Kingdom alisdair.ryding@nnuh.nhs.uk. ·J Am Heart Assoc · Pubmed #28468787.

ABSTRACT: BACKGROUND: Plaque erosion causes 30% of ST-segment elevation myocardial infarctions, but the underlying cause is unknown. Inflammatory infiltrates are less abundant in erosion compared with rupture in autopsy studies. We hypothesized that erosion and rupture are associated with significant differences in intracoronary cytokines in vivo. METHODS AND RESULTS: Forty ST-segment elevation myocardial infarction patients with <6 hours of chest pain were classified as ruptured fibrous cap (RFC) or intact fibrous cap (IFC) using optical coherence tomography. Plasma samples from the infarct-related artery and a peripheral artery were analyzed for expression of 102 cytokines using arrays; results were confirmed with ELISA. Thrombectomy samples were analyzed for differential mRNA expression using quantitative real-time polymerase chain reaction. Twenty-three lesions were classified as RFC (58%), 15 as IFC (38%), and 2 were undefined (4%). In addition, 12% (12 of 102) of cytokines were differentially expressed in both coronary and peripheral plasma. I-TAC was preferentially expressed in RFC (significance analysis of microarrays adjusted CONCLUSIONS: These results demonstrate differential intracoronary cytokine expression in RFC and IFC. Elevated thrombospondin 1 and epidermal growth factor may play an etiological role in erosion.

17 Article One-year costs of bilateral or single internal mammary grafts in the Arterial Revascularisation Trial. 2017

Gray, Alastair M / Murphy, Jacqueline / Altman, Douglas G / Benedetto, Umberto / Campbell, Helen / Flather, Marcus / Gerry, Stephen / Lees, Belinda / Taggart, David P. ·Nuffield Department of Population Health, Health Economics Research Centre, University of Oxford, Headington, UK. · Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, Centre for Statistics in Medicine, Botnar Research Centre, University of Oxford, Oxford, UK. · School of Clinical Sciences, University of Bristol and Bristol Royal Infirmary, Bristol, UK. · Norwich Medical School, University of East Anglia and Norfolk and Norwich University Hospital, Norwich, UK. · Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. ·Heart · Pubmed #28450552.

ABSTRACT: OBJECTIVE: Coronary artery bypass grafting (CABG) using bilateral internal mammary arteries (BIMA) may improve survival over CABG using single internal mammary arteries (SIMA), but may be surgically more complex (and therefore costly) and associated with impaired sternal wound healing. We report, for the first time, a detailed comparison of healthcare resource use and costs over 12 months, as part of the Arterial Revascularisation (ART) Trial. METHODS: 3102 patients in 28 hospitals in seven countries were randomised to CABG surgery using BIMA (n=1548) or SIMA (n=1554). Detailed resource use data were collected covering surgery, the initial hospital episode, and for 12 months post randomisation. Using UK unit costs, total costs were calculated and compared between trial arms and for subgroups. RESULTS: Patients randomised to BIMA spent 20 min longer in theatre (95% CI 15 to 25, p<0.001) and also required more treatment for sternal wound problems. Mean (SD) total costs per patient at 12 months were £13 839 (£10 534) for BIMA and £12 717 (£9719) for SIMA (mean cost difference £1122, 95% CI £407 to £1838, p=0.002). No tests for interaction between subgroups and treatment allocation were significant. CONCLUSIONS: At 12 months from randomisation, mean costs were approximately 9% higher in BIMA than SIMA patients, primarily due to longer time in theatre and in-hospital stay, and slightly higher costs related to sternal wound problems during follow-up. Follow-up to the primary trial endpoint of 10 years will reveal whether longer-term differences emerge in graft patency or in overall survival. TRIAL REGISTRATION NUMBER: Controlled-trials.com (ISRCTN46552265).

18 Article Impact of dual antiplatelet therapy after coronary artery bypass surgery on 1-year outcomes in the Arterial Revascularization Trial. 2017

Benedetto, Umberto / Altman, Douglas G / Gerry, Stephen / Gray, Alastair / Lees, Belinda / Flather, Marcus / Taggart, David P / Anonymous4750902. ·Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, UK. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, UK. · Department of Public Health, Health Economics Research Centre, University of Oxford, Headington, Oxford, UK. · Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. · Research and Development Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK. ·Eur J Cardiothorac Surg · Pubmed #28387790.

ABSTRACT: OBJECTIVES: There is still little evidence to boldport routine dual antiplatelet therapy (DAPT) with P2Y12 antagonists following coronary artery bypass grafting (CABG). The Arterial Revascularization Trial (ART) was designed to compare 10-year survival after bilateral versus single internal thoracic artery grafting. We aimed to get insights into the effect of DAPT (with clopidogrel) following CABG on 1-year outcomes by performing a post hoc ART analysis. METHODS: Among patients enrolled in the ART (n = 3102), 609 (21%) and 2308 (79%) were discharged on DAPT or aspirin alone, respectively. The primary end-point was the incidence of major adverse cerebrovascular and cardiac events (MACCE) at 1 year including cardiac death, myocardial infarction, cerebrovascular accident and reintervention; safety end-point was bleeding requiring hospitalization. Propensity score (PS) matching was used to create comparable groups. RESULTS: Among 609 PS-matched pairs, MACCE occurred in 34 (5.6%) and 34 (5.6%) in the DAPT and aspirin alone groups, respectively, with no significant difference between the 2 groups [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.59-1.59; P = 0.90]. Only 188 (31%) subjects completed 1 year of DAPT, and in this subgroup, MACCE rate was 5.8% (HR 1.11, 95% CI 0.53-2.30; P = 0.78). In the overall sample, bleeding rate was higher in DAPT group (2.3% vs 1.1%; P = 0.02), although this difference was no longer significant after matching (2.3% vs 1.8%; P = 0.54). CONCLUSIONS: Based on these findings, when compared with aspirin alone, DAPT with clopidogrel prescribed at discharge was not associated with a significant reduction of adverse cardiac and cerebrovascular events at 1 year following CABG.

19 Article Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts. 2016

Taggart, David P / Altman, Douglas G / Gray, Alastair M / Lees, Belinda / Gerry, Stephen / Benedetto, Umberto / Flather, Marcus / Anonymous901133. ·From Nuffield Department of Surgical Sciences (D.P.T., B.L.), Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Botnar Research Centre (D.G.A., S.G.), and the Health Economics Research Centre, Nuffield Department of Population Health (A.M.G.), University of Oxford, Oxford, the School of Clinical Sciences, University of Bristol and Bristol Royal Infirmary, Bristol (U.B.), and Norwich Medical School, University of East Anglia and Norfolk and Norwich University Hospital, Norwich (M.F.) - all in the United Kingdom. ·N Engl J Med · Pubmed #27959712.

ABSTRACT: BACKGROUND: The use of bilateral internal thoracic (mammary) arteries for coronary-artery bypass grafting (CABG) may improve long-term outcomes as compared with the use of a single internal-thoracic-artery plus vein grafts. METHODS: We randomly assigned patients scheduled for CABG to undergo single or bilateral internal-thoracic-artery grafting in 28 cardiac surgical centers in seven countries. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. Interim analyses were prespecified at 5 years of follow-up. RESULTS: A total of 3102 patients were enrolled; 1554 were randomly assigned to undergo single internal-thoracic-artery grafting (the single-graft group) and 1548 to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group). At 5 years of follow-up, the rate of death was 8.7% in the bilateral-graft group and 8.4% in the single-graft group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.32; P=0.77), and the rate of the composite of death from any cause, myocardial infarction, or stroke was 12.2% and 12.7%, respectively (hazard ratio, 0.96; 95% CI, 0.79 to 1.17; P=0.69). The rate of sternal wound complication was 3.5% in the bilateral-graft group versus 1.9% in the single-graft group (P=0.005), and the rate of sternal reconstruction was 1.9% versus 0.6% (P=0.002). CONCLUSIONS: Among patients undergoing CABG, there was no significant difference between those receiving single internal-thoracic-artery grafts and those receiving bilateral internal-thoracic-artery grafts with regard to mortality or the rates of cardiovascular events at 5 years of follow-up. There were more sternal wound complications with bilateral internal-thoracic-artery grafting than with single internal-thoracic-artery grafting. Ten-year follow-up is ongoing. (Funded by the British Heart Foundation and others; ART Current Controlled Trials number, ISRCTN46552265 .).

20 Article Infarct size following complete revascularization in patients presenting with STEMI: a comparison of immediate and staged in-hospital non-infarct related artery PCI subgroups in the CvLPRIT study. 2016

Khan, Jamal N / Nazir, Sheraz A / Greenwood, John P / Dalby, Miles / Curzen, Nick / Hetherington, Simon / Kelly, Damian J / Blackman, Daniel / Ring, Arne / Peebles, Charles / Wong, Joyce / Sasikaran, Thiagarajah / Flather, Marcus / Swanton, Howard / Gershlick, Anthony H / McCann, Gerry P. ·Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Cardiovascular Biomedical Research Unit, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK. · Multidisciplinary Cardiovascular Research Centre and The Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK. · Harefield Hospital, Royal Brompton and Harefield Foundation Trust, NIHR Cardiovascular Biomedical Research Unit, Middlesex, UK. · University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK. · Kettering General Hospital, Kettering, NN16 8UZ, UK. · Royal Derby Hospital, Derby, UK. · Leicester Clinical Trials Unit, University of Leicester, UK and Department of Mathematical Statistics and Actuarial Science, University of Leicester, University of the Free State, Bloemfontein, South Africa. · Norfolk and Norwich University Hospitals NHS Foundation Trust and Norwich Medical School, University of East Anglia, Norwich, UK. · The Heart Hospital, University College London Hospitals, London, UK. · Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Cardiovascular Biomedical Research Unit, University Hospitals of Leicester NHS Trust, Glenfield Hospital, Leicester, UK. gpm12@le.ac.uk. ·J Cardiovasc Magn Reson · Pubmed #27842548.

ABSTRACT: BACKGROUND: The CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI. METHODS: The Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease. These data refer to a post-hoc analysis in 93 patients randomized to the CR arm (63 immediate, 30 staged) who completed a pre-discharge CMR scan (median 2 and 4 days respectively) after PPCI. The decision to stage non-IRA revascularization was at the discretion of the treating interventional cardiologist. RESULTS: Patients treated with a staged approach had more visible thrombus (26/30 vs. 31/62, p = 0.001), higher SYNTAX score in the IRA (9.5, 8-16 vs. 8.0, 5.5-11, p = 0.04) and a greater incidence of no-reflow (23.3 % vs. 1.6 % p < 0.001) than those treated with immediate CR. After adjustment for confounders, staged patients had larger infarct size (19.7 % [11.7-37.6] vs. 11.6 % [6.8-18.2] of LV Mass, p = 0.012) and lower ejection fraction (42.2 ± 10 % vs. 47.4 ± 9 %, p = 0.019) compared with immediate CR. CONCLUSIONS: Of patients randomized to CR in the CMR substudy of CvLPRIT, those in whom the operator chose to stage revascularization had larger infarct size and lower ejection fraction, which persisted after adjusting for important covariates than those who underwent immediate CR. Prospective randomized trials are needed to assess whether immediate CR results in better clinical outcomes than staged CR. TRIAL REGISTRATION: ISRCTN70913605 , Registered 24th February 2011.

21 Article Pedicled and skeletonized single and bilateral internal thoracic artery grafts and the incidence of sternal wound complications: Insights from the Arterial Revascularization Trial. 2016

Benedetto, Umberto / Altman, Douglas G / Gerry, Stephen / Gray, Alastair / Lees, Belinda / Pawlaczyk, Rafal / Flather, Marcus / Taggart, David P / Anonymous7060865. ·Bristol Heart Institute, University of Bristol, School of Clinical Sciences, Bristol, United Kingdom. Electronic address: Umberto.benedetto@bristol.ac.uk. · Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom. · Department of Public Health, Health Economics Research Centre, University of Oxford, Headington, Oxford, United Kingdom. · Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. · Department of Cardiovascular Surgery, Medical University of Gdansk, Poland. · Research and Development Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom. ·J Thorac Cardiovasc Surg · Pubmed #27112712.

ABSTRACT: OBJECTIVES: The question of whether skeletonized internal thoracic artery harvesting reduces the incidence of sternal wound complications in comparison with the pedicled technique, in the context of single or bilateral internal thoracic arteries, remains controversial. We studied the impact of the internal thoracic artery harvesting strategy on sternal wound complication in the Arterial Revascularization Trial. METHODS: Patients enrolled in the Arterial Revascularization Trial (n = 3102) were randomized to coronary artery bypass grafting with single or bilateral internal thoracic arteries. Sternal wound complication rates were examined according to the harvesting technique that was documented in 2056 patients. The internal thoracic artery harvesting technique, based on the surgeon's preference, resulted in 4 groups: pedicled single internal thoracic artery (n = 607), pedicled bilateral internal thoracic artery (n = 459), skeletonized single internal thoracic artery (n = 512), and skeletonized bilateral internal thoracic artery (n = 478). Propensity scores weighting was used to estimate the impact of the harvesting technique on sternal wound complications. RESULTS: A total of 219 of 2056 patients (10.6%) experienced a sternal wound complication within 1 year from the index operation. Of those, only 25 patients (1.2%) required sternal wound reconstruction. Pedicled bilateral internal thoracic artery (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.23-2.63) but not skeletonized bilateral internal thoracic artery (OR, 1.00; 95% CI, 0.65-1.53) or skeletonized single internal thoracic artery (OR, 0.89; 95% CI, 0.57-1.38) was associated with a significantly increased risk of any sternal wound complications compared with pedicled single internal thoracic artery. CONCLUSIONS: The present Arterial Revascularization Trial substudy suggests that, with a skeletonization technique, the risk of sternal wound complication with bilateral internal thoracic artery grafting is similar to that after standard pedicled single internal thoracic artery harvesting, whereas skeletonized single internal thoracic artery harvesting did not add any further benefit when compared with pedicled single internal thoracic artery harvesting.

22 Article Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease. 2016

Williams, Michelle C / Hunter, Amanda / Shah, Anoop S V / Assi, Valentina / Lewis, Stephanie / Smith, Joel / Berry, Colin / Boon, Nicholas A / Clark, Elizabeth / Flather, Marcus / Forbes, John / McLean, Scott / Roditi, Giles / van Beek, Edwin J R / Timmis, Adam D / Newby, David E / Anonymous10501108. ·British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. · Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom. · Health Economics Research Centre, University of Oxford, Oxford, United Kingdom. · Institute for Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. · Norwich Medical School, University of East Anglia, Norwich, United Kingdom. · Health Research Institute, University of Limerick, Limerick, Ireland. · National Health Service, Fife, United Kingdom. · William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. · British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: d.e.newby@ed.ac.uk. ·J Am Coll Cardiol · Pubmed #27081014.

ABSTRACT: BACKGROUND: In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA). OBJECTIVES: The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes. METHODS: In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records. RESULTS: Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621). CONCLUSIONS: In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).

23 Article Effects of on-pump and off-pump surgery in the Arterial Revascularization Trial. 2015

Taggart, David P / Altman, Douglas G / Gray, Alastair M / Lees, Belinda / Nugara, Fiona / Yu, Ly-Mee / Flather, Marcus / Anonymous2380806. ·Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK david.taggart@orh.nhs.uk. · Centre for Statistics in Medicine, University of Oxford, Oxford, UK Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, Oxford, UK. · Department of Public Health, Health Economics Research Centre, University of Oxford, Headington, Oxford, UK. · Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Trust, London, UK National Heart and Lung Institute, Imperial College London, London, UK. · Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Trust, London, UK. ·Eur J Cardiothorac Surg · Pubmed #25217501.

ABSTRACT: OBJECTIVES: The Arterial Revascularization Trial (ART) is a randomized comparison of bilateral internal mammary artery (BIMA) versus single internal mammary artery (SIMA) grafting in coronary artery bypass graft (CABG) surgery and is one of the largest randomized trials of surgery ever conducted. ART is also one of the largest studies of contemporary CABG with a high proportion of off-pump surgeries (41%). The objective of this post hoc analysis was to evaluate the surgical process and 1-year outcomes for surgery performed on-pump compared with off-pump. METHODS: ART randomized 3102 patients with multivessel coronary artery disease (CAD) to SIMA or BIMA grafts to determine if BIMA grafts have an additional survival advantage at 10 years. The 1-year interim analysis showed an overall very low mortality and major morbidity rate irrespective of whether the procedure was with an SIMA or BIMA. The surgical process and 1-year outcomes were analysed according to whether surgery was performed on-pump or off-pump. RESULTS: Baseline variables were not statistically significantly different between on- and off-pump surgery within each treatment group after taking account of the effects of clustering by individual surgeons. At both 30 days and 1 year, there was a low incidence of death (1.2%, 2.3%), stroke (1.1%, 1.7%), myocardial infarction (MI) (1.4%, 1.9%), repeat revascularization (0.5%, 1.5%) and wound reconstruction (1.2%). A similar average number of grafts were performed with on- and off-pump surgery (median = 3), but the duration of surgery was 20-30 min and ventilation time ∼ 2 h shorter with off-pump surgery. Blood loss and platelet transfusions were lower in the off-pump group, with no difference in the need for balloon pump or renal support. Sternal wound reconstruction was similar with off-pump surgery in the SIMA group (0.5 vs 0.6%) and lower with off-pump surgery in the BIMA group (1.4 vs 2.2%). Repeat revascularization was marginally higher in off-pump patients at 30 days (0.8 vs 0.3%) and at 1 year (1.7 vs 1.3%). CONCLUSIONS: The outcomes of contemporary CABG are excellent with low mortality, stroke, myocardial infarction and need for wound reconstruction and repeat revascularization whether performed on-pump or off-pump. CLINICAL TRIAL REGISTRATION: Controlled-trials.com (ISRCTN46552265).

24 Article Darapladib for preventing ischemic events in stable coronary heart disease. 2014

Anonymous4370789 / White, Harvey D / Held, Claes / Stewart, Ralph / Tarka, Elizabeth / Brown, Rebekkah / Davies, Richard Y / Budaj, Andrzej / Harrington, Robert A / Steg, P Gabriel / Ardissino, Diego / Armstrong, Paul W / Avezum, Alvaro / Aylward, Philip E / Bryce, Alfonso / Chen, Hong / Chen, Ming-Fong / Corbalan, Ramon / Dalby, Anthony J / Danchin, Nicolas / De Winter, Robbert J / Denchev, Stefan / Diaz, Rafael / Elisaf, Moses / Flather, Marcus D / Goudev, Assen R / Granger, Christopher B / Grinfeld, Liliana / Hochman, Judith S / Husted, Steen / Kim, Hyo-Soo / Koenig, Wolfgang / Linhart, Ales / Lonn, Eva / López-Sendón, José / Manolis, Athanasios J / Mohler, Emile R / Nicolau, José C / Pais, Prem / Parkhomenko, Alexander / Pedersen, Terje R / Pella, Daniel / Ramos-Corrales, Marco A / Ruda, Mikhail / Sereg, Mátyás / Siddique, Saulat / Sinnaeve, Peter / Smith, Peter / Sritara, Piyamitr / Swart, Henk P / Sy, Rody G / Teramoto, Tamio / Tse, Hung-Fat / Watson, David / Weaver, W Douglas / Weiss, Robert / Viigimaa, Margus / Vinereanu, Dragos / Zhu, Junren / Cannon, Christopher P / Wallentin, Lars. · ·N Engl J Med · Pubmed #24678955.

ABSTRACT: BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

25 Article Complete Versus culprit-Lesion only PRimary PCI Trial (CVLPRIT): a multicentre trial testing management strategies when multivessel disease is detected at the time of primary PCI: rationale and design. 2013

Kelly, Damian J / McCann, Gerald P / Blackman, Daniel / Curzen, Nicholas P / Dalby, Miles / Greenwood, John P / Fairbrother, Kathryn / Shipley, Lorraine / Kelion, Andrew / Heatherington, Simon / Khan, Jamal N / Nazir, Sheraz / Alahmar, Albert / Flather, Marcus / Swanton, Howard / Schofield, Peter / Gunning, Mark / Hall, Roger / Gershlick, Anthony H. ·Department of Cardiology, University Hospitals of Leicester, Leicester, United Kingdom. ·EuroIntervention · Pubmed #23425543.

ABSTRACT: AIMS: Primary percutaneous coronary intervention (PPCI) is the preferred strategy for acute ST-segment elevation myocardial infarction (STEMI), with evidence of improved clinical outcomes compared to fibrinolytic therapy. However, there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI, with little robust data on best management of angiographically significant stenoses detected in non-infarct-related (N-IRA) coronary arteries. CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI. METHODS AND RESULTS: CVLPRIT (Complete Versus culprit-Lesion only PRimary PCI Trial) is an open-label, prospective, randomised, multicentre trial. STEMI patients undergo verbal "assent" on presentation. Patients are included when angiographic MVD has been detected, and randomised to culprit (IRA)-only PCI (n=150) or in-patient complete multivessel PCI (n=150). Cumulative major adverse cardiac events (MACE) - all-cause mortality, recurrent MI, heart failure, need for revascularisation (PCI or CABG) will be recorded at 12 months. Secondary endpoints include safety endpoints of confirmed ischaemic stroke, intracranial haemorrhage, major non-intracranial bleeding, and repair of vascular complications. A cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage index and microvascular obstruction. A cost efficacy analysis will be undertaken. CONCLUSIONS: The management of multivessel coronary artery disease in the setting of PPCI for STEMI, including the timing of when to perform non-culprit-artery revascularisation if undertaken, remains unresolved. CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infarct period.

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