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Background: The optimal antiplatelet strategy in the second year after percutaneous coronary intervention (PCI) remains unclear.Aims: We aimed to compare ticagrelor monotherapy with aspirin monotherapy on clinical outcomes beyond 1 year post-PCI.Methods: This post hoc subanalysis of the open-label, all-comers, randomised GLOBAL LEADERS trial, which compared 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) with 12-month aspirin monotherapy following 12-month DAPT, only included patients who, at 12 months, were free from ischaemic and bleeding events and were adherent to their assigned antiplatelet therapy. The incidences of ischaemic events (all-cause death, any myocardial infarction, or any stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) during the second year (12-24 months) were compared between patients receiving either ticagrelor or aspirin monotherapy.Results: The present analysis included 11,121 (ticagrelor monotherapy n=5,308, and aspirin monotherapy n=5,813) of the 15,991 patients enrolled in GLOBAL LEADERS. During the second year, the ischaemic composite endpoint was lower with ticagrelor monotherapy compared to aspirin monotherapy (1.9% vs 2.6%: log-rank p=0.014, adjusted hazard ratio [HR] 0.74, 95% confidence interval [CI]: 0.58-0.96; p=0.022), which was primarily driven by a reduced risk of myocardial infarction. In contrast, BARC type 3 or 5 bleeding was numerically higher with ticagrelor monotherapy (0.5% vs 0.3%: log-rank p=0.051, adjusted HR 1.89, 95% CI: 1.03-3.45; p=0.005).Conclusions: Patients free from events at the end of the first year post-PCI and who adhered to their prescribed regimen had a reduced risk of ischaemic events compared to aspirin mootherapy in the second year post-PCI.ClinicalTrials.gov: NCT01813435

BACKGROUND: Personalized long term vital prognosis plays a key role in deciding between percutaneous coronary intervention (PCI) and CABG in patients with complex coronary artery disease. The FASTTRACK CABG trial enrolls patients with the sole guidance of coronary computed tomographic angiography (CCTA) and fractional flow reserve CCTA (FFRCT). The feasibility/non-feasibility of this approach is determined by the surgeon request to have access to the invasive coronary angiography. METHODS: This interim analysis, which was requested by the Data and Safety Monitoring Board (DSMB), compared the treatment decision of the "on site" Heart team to the recommended treatment as per the SYNTAX Score II 2020 (SS-2020), which was prospectively assessed by the central core laboratory in the first 57 consecutive patients (half of the planned population) enrolled in this First in Man study. RESULTS: The average anatomical SYTAX Score is 35.6 ± 11.5. The SS-2020 predicted 5-year MACE and 10-year all-cause mortality are 14.7 % and 21.6 % following CABG, and 23.0 % and 30.4 % following PCI. Among the enrolled patients the SS-2020 predicts long-term PCI outcomes similar to CABG (absolute risk difference ≤0 % in favor of PCI) in only two patients whilst the remaining 55 patients had a predicted survival benefit with CABG. CONCLUSIONS: According to the SS-2020, the first 57 patients recruited into the FASTTRACK CABG trial received the appropriate modality of revascularization and the DSMB allowed the investigators to complete the study.

Coronary computed tomographic angiography (CCTA) is becoming the first-line investigation for establishing the presence of coronary artery disease and, with fractional flow reserve (FFRCT), its haemodynamic significance. In patients without significant epicardial obstruction, its role is either to rule out atherosclerosis or to detect subclinical plaque that should be monitored for plaque progression/regression following prevention therapy and provide risk classification. Ischaemic non-obstructive coronary arteries are also expected to be assessed by non-invasive imaging, including CCTA. In patients with significant epicardial obstruction, CCTA can assist in planning revascularisation by determining the disease complexity, vessel size, lesion length and tissue composition of the atherosclerotic plaque, as well as the best fluoroscopic viewing angle; it may also help in selecting adjunctive percutaneous devices (e.g., rotational atherectomy) and in determining the best landing zone for stents or bypass grafts.

A 79-year-old male with chronic coronary syndrome with complex coronary artery disease was included in the first-in-man trial of surgical revascularization guided solely by coronary computed tomography angiography (CCTA) and fractional flow reserve derived from CCTA (FFRCT). In CCTA analysis, the patient had calcified three-vessel disease, with a global anatomical SYNTAX score of 27. In contrast, in the initial FFRCT, only the ramus intermediate stenosis was physiologically significant, with no other vessels having an FFRCT ≤ 0.80 (functional SYNTAX score of 2). Discordance between the results of the CCTA and FFRCT necessitated an in-depth analysis by using both invasive and non-invasive coronary angiography. Angiography-derived fractional flow reserve (FFR) confirmed that the stenosis in the proximal left anterior descending artery (LAD) was physiologically significant, while it remained functionally negative in the second assessment of FFRCT. Extensive calcification is the most plausible explanation for the underestimation of the stenosis of proximal LAD in CCTA-derived FFR technology.

PURPOSE Although drug-coated balloon (DCB) treatment is known to be effective for de novo lesions, the influence of sex on angiographic and clinical outcomes remains unknown. This study aimed to investigate the angiographic and clinical impact of DCB treatment in patients with de novo coronary lesions according to sex. MATERIALS AND METHODS A total of 227 patients successfully treated with DCB were retrospectively enrolled and divided into two groups according to sex. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF), which included cardiac death, target vessel myocardial infarction, target lesion revascularization, and target vessel thrombosis. RESULTS The study enrolled 60 women (26.4%) and 167 men (73.6%). Compared to men, women had a smaller vessel size, larger DCB to reference vessel ratio, and more dissections after DCB treatment (55.0% vs. 37.1%, p=0.016). Women also had a significantly higher LLL compared to men (0.12±0.26 mm vs. 0.02±0.22 mm, p=0.012) at the 6-month follow-up angiography. During a median follow-up of 3.4 years (range 12.7-28.9 months), TVF was similar (women 6.7% vs. men 7.8%, p=0.944). In multivariable analysis, women were independently associated with a higher LLL. CONCLUSION LLL was higher in women, but there was no difference in TVF between women and men. Based on multivariable analysis, the women sex was an independent predictor of higher LLL (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; NCT04619277).

Background Angiography-derived physiological assessment of coronary lesions has emerged as an alternative to wire based assessment aiming at less-invasiveness and shorter procedural time as well as cost effectiveness in physiology-guided decision making. However, current available image-derived physiology software have limitations including the requirement of multiple projections and are time consuming.Methods/Design The ReVEAL iFR (Radiographic imaging Validation and EvALuation for Angio-iFR) trial is a multicenter, multicontinental, validation study which aims to validate the diagnostic accuracy of the Angio-iFR medical software device (Philips, San Diego, US) in patients undergoing angiography for Chronic Coronary Syndrome (CCS). The Angio-iFR will enable operators to predict both the iFR and FFR value within a few seconds from a single projection of cine angiography by using a lumped parameter fluid dynamics model. Approximately 440 patients with at least one de-novo 40% to 90% stenosis by visual angiographic assessment will be enrolled in the study. The primary endpoint is the sensitivity and specificity of the iFR and FFR for a given lesion compared to the corresponding invasive measures. The enrollment started in August 2019, and was completed in March 2021.Summary The Angio-iFR system has the potential of simplifying physiological evaluation of coronary stenosis compared with available systems, providing estimates of both FFR and iFR. The ReVEAL iFR study will investigate the predictive performance of the novel Angio-iFR software in CCS patients. Ultimately, based on its unique characteristics, the Angio-iFR system may contribute to improve adoption of functional coronary assessment and the workflow in the catheter laboratory.

Background: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone. Methods: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non–ST-segment–elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events. Results: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3–5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613–£7015); and angiography+FFR, £4510 (£2721–£7415; P =0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60–87); and angiography+FFR, 75 (interquartile range, 60–90; P =0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR ( P =0.64). Conclusions: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01070771.

Background: The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear. Objectives: The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD). Methods: In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models. Results: Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; pinteraction = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; pinteraction = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: −0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients. Conclusions: Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050) (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Background: Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow-up. Objectives: The aim of this study was to investigate the impact of bifurcation lesions on individual predicted and observed all-cause 10-year mortality in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. Methods: In the SYNTAXES (SYNTAX Extended Survival) study, 10-year observed and individual predicted mortality derived from the SYNTAX score 2020 (SS-2020) was compared between patients with ≥1 bifurcation (n = 1,300) and those with no bifurcations (n = 487). Results: Among patients treated with PCI, patients with >1 bifurcation lesion compared with those without bifurcation lesions had a significantly higher risk for all-cause death (19.8% vs 30.1%; HR: 1.55; 95% CI: 1.12-2.14; P = 0.007), whereas following CABG, mortality was similar in patients with and those without bifurcation lesions (23.3% vs 23.0%; HR: 0.81; 95% CI: 0.59-1.12; P = 0.207; Pinteraction = 0.006). In PCI patients, a 2-stent vs a 1-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51; 95% CI: 1.06-2.14; P = 0.021). According to the SS-2020, among those with ≥1 bifurcation, there was equipoise for all-cause mortality between PCI and CABG in 2 quartiles of the population, whereas CABG was superior to PCI in the 2 remaining quartiles. Conclusions: Bifurcation lesions require special attention from the heart team, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity and calculation of individualized 10-year prognosis using the SS-2020 may therefore be helpful in decision making. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)

The Bifurcation Academic Research Consortium (Bif-ARC) project originated from the need to overcome the paucity of standardization and comparability between studies involving bifurcation coronary lesions. This document is the result of a collaborative effort between academic research organizations and the most renowned interventional cardiology societies focused on bifurcation lesions in Europe, the United States, and Asia. This consensus provides standardized definitions for bifurcation lesions; the criteria to judge the side branch relevance; the procedural, mechanistic, and clinical endpoints for every type of bifurcation study; and the follow-up methods. Considering the complexity of bifurcation lesions and their evaluation, detailed instructions and technical aspects for site and core laboratory analysis of bifurcation lesions are also reported. The recommendations included within this consensus will facilitate pooled analyses and the effective comparison of data in the future, improving the clinical relevance of trials in bifurcation lesions, and the quality of care in this subset of patients.

Objectives: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG). Background: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score. Methods: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated. Results: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p

Background: The poorer prognosis of coronary artery disease in females compared with males is related mainly to differences in baseline characteristics. In the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial, the effect of treatment with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting surgery (CABG) on mortality at 5 years differed significantly between females and males; however, the optimal revascularization beyond 5 years according to sex has not been evaluated. Objectives: The aim of this study was to investigate the impact of sex on mortality and sex-treatment interaction at 10 years. Methods: The SYNTAXES (SYNTAX Extended Survival) study evaluated vital status up to 10 years in 1,800 patients with de novo 3-vessel and/or left main coronary artery disease randomized to treatment with PCI or CABG in the SYNTAX trial. All-cause death at 10 years was separately evaluated in female and male patients with complex coronary artery disease. Results: Of 1,800 patients, 402 (22.3%) were female and 1,398 (77.7%) were males. Females had a higher 10-year mortality rate compared with males (32.8% vs. 24.7%; log-rank p = 0.002), but female sex was not an independent predictor of mortality (adjusted hazard ratio: 1.02; 95% confidence interval: 0.76 to 1.36). Mortality at 10 years tended to be lower after CABG than after PCI, with a similar treatment effect for female and male patients (adjusted hazard ratio for females: 0.90 [95% confidence interval: 0.54 to 1.51]; adjusted hazard ratio for males: 0.76 [95% confidence interval: 0.56 to 1.02]; p for interaction = 0.952). Conclusions: Female sex was not an independent predictor of mortality at 10 years in patients with complex coronary artery disease. The interaction between sex and treatment with PCI or CABG that was observed at 5 years was no longer present at 10 years. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)

Background The aim of this study was to investigate the impact of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for bifurcation lesions. Methods GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing 1-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The primary endpoint was a composite of all-cause death or new Q-wave myocardial infarction (MI) at 2 years. Results Among the 15,845 patients included in this subgroup analysis, 2,498 patients (15.8%) underwent PCI for at least one bifurcation lesion. The incidence of the primary endpoint was similar between the bifurcation and nonbifurcation groups (4.7 vs. 4.0%, p = .083). The experimental treatment had no significant effect on the primary endpoint according to the presence/absence of a bifurcation lesion (bifurcation: hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.51-1.07; nonbifurcation: HR: 0.90, 95% CI: 0.76-1.07, p for interaction = .343), but was associated with significant reduction in definite or probable stent thrombosis (p for interaction = .022) and significant excess of stroke (p for interaction = .018) when compared with the reference treatment. Conclusions After PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial. AstraZeneca; Biosensors International Group; Medicines company

Background The utility of the PRECISE-DAPT score in predicting short-term major bleeding, either alone, or in comparison with the CRUSADE and ACUITY scores, has not been investigated. This analysis compared the predictive performances of the three bleeding scores in stratifying the risk of 30-day major bleeding postpercutaneous coronary intervention in patients with dual-antiplatelet therapy.Methods In this post hoc subanalysis of the GLOBAL LEADERS trial, the primary safety objective (bleeding according to the Bleeding Academic Research Consortium [BARC] criteria [type 3 or 5]) was assessed at 30 days according to the three scores in the overall population, and in patients with acute (ACS) and chronic coronary syndrome (CCS).Results In a total of 15,968 patients, we calculated all three scores in 14,709 (92.1%). Irrespective of clinical presentation, the PRECISE-DAPT (c-statistics: 0.648, 0.653, and 0.641, respectively), CRUSADE (c-statistics: 0.641, 0.639, and 0.644, respectively), and ACUITY (c-statistics: 0.633, 0.638, and 0.623, respectively) scores were no significant between-score differences in discriminatory performance for BARC 3 or 5 bleeding up to 30 days, and similarly the PRECISE-DAPT score had a comparable discriminative capacity according to the integrated discrimination improvement when compared with the other scores. In ACS, the CRUSADE score had a poor calibration ability (Hosmer–Lemeshow goodness-of-fit [GOF] chi-square = 15.561, p = 0.049), whereas in CCS, the PRECISE-DAPT score had poor calibration (GOF chi-square = 15.758, p = 0.046).Conclusion The PRECISE-DAPT score might be clinically useful in the overall population and ACS patients for the prediction of short-term major bleeding considering its discriminative and calibration abilities.

Backgrounds: Data on optimal antiplatelet therapy in patients undergoing stenting of the proximal left anterior descending artery (LAD) are limited. Methods: This is a post-hoc analysis of the GLOBAL LEADERS trial, a prospective, multi-center, randomized controlled trial, comparing the experimental strategy (1-month dual anti-platelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) with the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in relation to stenting of the proximal LAD. The primary endpoint was the composite of all-cause death or new Q-wave myocardial infarction (MI) and key secondary safety endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at two years. Results: Among 15,845 patients included in the analysis, 3823 (23.9%) patients underwent stenting of the proximal LAD, while 12,022 (75.2%) did not. In the proximal LAD stenting group, there was no significant difference in the risk of the primary endpoint between the two antiplatelet strategies (3.38% vs. 3.93%; hazard ratio [HR]:0.86; 95% CI:0.62–1.20; Pinteraction = 0.951). However, the risk of any MI (2.63% vs. 3.88%; HR:0.68; 95% CI:0.47–0.97; Pinteraction = 0.015) and any revascularization (7.84% vs. 9.94%; HR:0.78; 95% CI:0.63–0.97; Pinteraction = 0.058) was significantly lower in the experimental strategy group, while demonstrating a similar risk of BARC type 3 or 5 bleeding between the two antiplatelet strategies (1.93% vs. 1.99%; HR:0.98; 95% CI:0.62–1.54; Pinteraction = 0.981). Conclusions: The present study showed patients having stenting to the proximal LAD could potentially benefit from the experimental strategy with lower ischaemic events without a trade-off in major bleeding at two years.

Background: Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI).Methods/Design: The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent's fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non–inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non–inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years.The PIONEER IV trial aims to demonstrate non–inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy.Clinical Trial Registration: ClinicalTrials.govUnique Identifier: NCT04923191Classifications: Interventional Cardiology

Contains fulltext : 245655.pdf (Publisher’s version ) (Open Access) Historically, aspirin has been the primary treatment for the prevention of ischaemic events in patients with coronary artery disease. For patients undergoing percutaneous coronary intervention (PCI) standard treatment has been 12 months of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel, followed by aspirin monotherapy; however, DAPT is undeniably associated with an increased risk of bleeding. For over a decade novel P2Y12 inhibitors, which have increased specificity, potency, and efficacy have been available, prompting studies which have tested whether these newer agents can be used in aspirin-free antiplatelet regimens to augment clinical benefits in patients post-PCI. Among these studies, the GLOBAL LEADERS trial is the largest by cohort size, and so far has provided a wealth of evidence in a variety of clinical settings and patient groups. This article summarizes the state-of-the-art evidence obtained from the GLOBAL LEADERS and other trials of aspirin-free strategies.

Background Coronary bypass artery grafting (CABG) has a higher procedural risk of stroke than percutaneous coronary intervention (PCI), but may offer better long-term survival. The optimal revascularization strategy for patients with prior cerebrovascular disease (CEVD) remains unclear. Methods and results The SYNTAXES study assessed the vital status out to 10 year of patients with three-vessel disease and/or left main coronary artery disease enrolled in the SYNTAX trial. The relative efficacy of PCI vs. CABG in terms of 10 year all-cause death was assessed according to prior CEVD. The primary endpoint was 10 year all-cause death. The status of prior CEVD was available in 1791 (99.5%) patients, of whom 253 patients had prior CEVD. Patients with prior CEVD were older and had more comorbidities (medically treated diabetes, insulin-dependent diabetes, metabolic syndrome, peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function, and congestive heart failure), compared with those without prior CEVD. Prior CEVD was an independent predictor of 10 year all-cause death (adjusted HR: 1.35; 95% CI: 1.04–1.73; p = 0.021). Patients with prior CEVD had a significantly higher risk of 10 year all-cause death (41.1 vs. 24.1%; HR: 1.92; 95% CI: 1.54–2.40; p -interaction = 0.624). Conclusion Prior CEVD was associated with a significantly increased risk of 10 year all-cause death which was similar in patients treated with PCI or CABG. These results do not support preferential referral for PCI rather than CABG in patients with prior CEVD. Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

AIMS We aimed to update the logistic clinical SYNTAX score to predict 2��year all-cause mortality after contemporary percutaneous coronary intervention (PCI). METHODS AND RESULTS We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital. Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2��year all-cause mortality and included into the new model. The c-indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95% CI 0.72-0.76), 0.75 (95% CI 0.73-0.77), and 0.78 (95% CI 0.76-0.80), respectively. The c-index of the new model was lower in the validation cohort than in the derivation cohort, but still showed improved discriminative ability of the newly developed model (0.72; 95% CI 0.67-0.77) compared to the refitted original model (0.69; 95% CI 0.64-0.74). The models overestimated the observed 2��year all-cause mortality of 1.11% in the Chinese external validation cohort by 0.54 percentage points, indicating the need for calibration of the model to the Chinese patient population. CONCLUSIONS The new model of the logistic clinical SYNTAX score better predicts 2��year all-cause mortality after PCI than the original model. The new model could guide clinical decision making by risk stratifying patients undergoing PCI.

Background: Radial artery access has been shown to reduce mortality and bleeding events, especially in patients with acute coronary syndromes. Despite this, interventional cardiologists experienced in femoral artery access still prefer that route for percutaneous coronary intervention. Little is known regarding the merits of each vascular access in patients stratified by their risk of bleeding. Methods: Patients from the Global Leaders trial were dichotomized into low or high risk of bleeding by the median of the PRECISE-DAPT score. Clinical outcomes were compared at 30 days. Results: In the overall population, there were no statistical differences between radial and femoral access in the rate of the primary end point, a composite of all-cause mortality, or new Q-wave myocardial infarction (MI) (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.42-1.15). Radial access was associated with a significantly lower rate of the secondary safety end point, Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding (HR 0.55, 95% CI 0.36-0.84). Compared by bleeding risk strata, in the high bleeding score population, the primary (HR 0.47, 95% CI 0.26-0.85; P = 0.012; Pinteraction = 0.019) and secondary safety (HR 0.57, 95% CI 0.35-0.95; P = 0.030; Pinteraction = 0.631) end points favoured radial access. In the low bleeding score population, however, the differences in the primary and secondary safety end points between radial and femoral artery access were no longer statistically significant. Conclusions: Our findings suggest that the outcomes of mortality or new Q-wave MI and BARC 3 or 5 bleeding favour radial access in patients with a high, but not those with a low, risk of bleeding. Because this was not a primary analysis, it should be considered hypothesis generating.

Patients undergoing staged percutaneous coronary intervention (SPCI) are exposed to extended duration of antiplatelet therapy, and a novel aspirin-free antiplatelet regimen after SPCI should be specifically evaluated among these patients. This is a prespecified substudy of the GLOBAL LEADERS which is a randomized, open-label trial, comparing an experimental regimen of 1-month dual antiplatelet therapy (DAPT; ticagrelor and aspirin) followed by 23-month ticagrelor monotherapy to a reference regimen of 12-month DAPT followed by 12-month aspirin monotherapy. Patients were stratified according to whether or not SPCI was performed. The impact of the timing of SPCI on clinical outcomes was also investigated. Of 15,968 randomized patients, 1,651 patients underwent SPCI within 3 months. These patients with SPCI had a significantly higher risk of bleeding and ischemic endpoints than those without SPCI. In patients undergoing SPCI, the primary endpoint (composite of all-cause death or new Q-wave myocardial infarction at 2 years) and secondary safety endpoint (Bleeding Academic Research Consortium [BARC]-defined bleeding 3 or 5) were similar in the 2 regimens. However, in patients presenting with acute coronary syndrome (ACS), the experimental regimen reduced a risk of BARC 3 or 5 bleeding (1.8% vs 4.5%; HR 0.387; 95% CI 0.179 to 0.836; p = 0.016). In patients undergoing SPCI later than 10 days after index procedure, this risk reduction was still prominent (0.8% vs 2.3%; HR 0.321; 95% CI 0.116 to 0.891; p = 0.029). In conclusion, patients undergoing SPCI are at high risk and may need special attention from clinicians. In ACS patients undergoing SPCI, a novel aspirin-free antiplatelet regimen appears to be associated with a lower bleeding risk than with standard DAPT.

Background: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. Methods: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m 2). Results: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35–1.98, p adj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61–1.11, p = 0.192, p int = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71–1.71, p = 0.656, p int = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (p int = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (p int = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. Conclusions: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. Clinical trial registration: The trial has been registered with ClinicalTrials.gov, number NCT01813435. Graphic abstract: [Figure not available: see fulltext.].

Contains fulltext : 225405.pdf (Publisher’s version ) (Open Access) BACKGROUND AND AIMS: The prognostic impact of pre-procedure heart rate (PHR) following percutaneous coronary intervention (PCI) has not yet been fully investigated. This post-hoc analysis sought to assess the impact of PHR on medium-term outcomes among patients having PCI, who were enrolled in the "all-comers" GLOBAL LEADERS trial. METHODS AND RESULTS: The primary endpoint (composite of all-cause death or new Q-wave myocardial infarction [MI]) and key secondary safety endpoint (bleeding according to Bleeding Academic Research Consortium [BARC] type 3 or 5) were assessed at 2 years. PHR was available in 15,855 patients, and when evaluated as a continuous variable (5 bpm increase) and following adjustment using multivariate Cox regression, it significantly correlated with the primary endpoint (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03-1.09, p 67 bpm was associated with increased all-cause mortality (HR 1.38, 95%CI 1.13-1.69, p = 0.002) and more frequent new Q-wave MI (HR 1.41, 95%CI 1.02-1.93, p = 0.037). No significant association was found between PHR and BARC 3 or 5 bleeding (HR 1.04, 95% CI 0.99-1.09, p = 0.099). There was no interaction with the primary (p-inter = 0.236) or secondary endpoint (p-inter = 0.154) when high and low PHR was analyzed according to different antiplatelet strategies. CONCLUSIONS: Elevated PHR was an independent predictor of all-cause mortality at 2 years following PCI in the "all-comer" GLOBAL LEADERS trial. The prognostic value of increased PHR on outcomes was not affected by the different antiplatelet strategies in this trial.

Background Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients. Methods In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events. Results At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66–2.80], p interaction = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56–0.99], p = 0.044, pinteraction = 0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29–0.82], p = 0.007, pinteraction = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29–0.82], p = 0.007, pinteraction = 0.013) in the second year. Conclusion Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating. Clinical Trial Registration: ClinicalTrials.gov (NCT01813435).

IMPORTANCE: Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI). OBJECTIVES: To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies. DESIGN, SETTING, AND PARTICIPANTS: This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019. INTERVENTIONS: Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding. RESULTS: Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045). CONCLUSIONS AND RELEVANCE: Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01813435

Background: The efficacy of antiplatelet therapies following percutaneous coronary intervention (PCI) may be affected by body mass index (BMI). Methods and results: This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. This is a prespecified subgroup analysis of the GLOBAL LEADERS trial, a prospective, multicenter, open-label, randomized controlled trial in an all-comer population undergoing PCI, comparing the experimental strategy (23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy [DAPT]) with a reference regimen (12-month aspirin monotherapy following 12-month DAPT). A total of 15,968 patients were stratified by baseline BMI with prespecified threshold of 27 kg/m2. Of those, 6973 (43.7%) patients with a BMI < 27 kg/m2 had a higher risk of all-cause mortality at 2 years than those with BMI ≥ 27 kg/m2 (adjusted HR 1.24, 95% CI 1.02–1.49). At 2 years, the rates of the primary endpoint (all-cause mortality or new Q-wave myocardial infarction) were similar between treatment strategies in either BMI group (pinteraction = 0.51). In acute coronary syndrome, however, the experimental strategy was associated with significant reduction of the primary endpoint compared to the reference strategy in patients with BMI < 27 kg/m2 (HR 0.69, 95% CI 0.51–0.94), but not in the ones with BMI ≥ 27 kg/m2 (pinteraction = 0.047). In chronic coronary syndrome, there was no between-group difference in the efficacy and safety of the two antiplatelet strategies. Conclusions: Overall, BMI did not influence the treatment effect seen with ticagrelor monotherapy; however, a beneficial effect of ticagrelor monotherapy was seen in ACS patients with BMI < 27 kg/m2. Trial registration: The trial has been registered with ClinicalTrials.gov, Number NCT01813435. Graphic abstract: [Figure not available: see fulltext.].

Background: Bleeding and myocardial infarction (MI) after percutaneous coronary intervention are independent risk factors for mortality. This study aimed to investigate the association of all-cause mortality after percutaneous coronary intervention with site-reported bleeding and MI, when considered as individual, repeated, or combined events. Methods: We used the data from the GLOBAL LEADERS trial (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-Platelet Therapy After Stent Implantation), an all-comers trial of 15 968 patients undergoing percutaneous coronary intervention. Bleeding was defined as Bleeding Academic Research Consortium (BARC) 2, 3, or 5, whereas MI included periprocedural and spontaneous MIs according to the Third Universal Definition. Results: At 2-year follow-up, 1061 and 498 patients (6.64% and 3.12%) experienced bleeding and MI, respectively. Patients with a bleeding event had a 10.8% mortality (hazard ratio [HR], 5.97 [95% CI, 4.76–7.49]; P P P =0.014, and HR of BARC 2 bleeding, 1.79 [95% CI, 1.02–3.15]; P =0.044). The mortality rates in patients with repetitive bleeding, repetitive MI, and both bleeding and MI were 16.1%, 19.2%, and 19.0%, and their HRs for 2-year mortality were 8.58 (95% CI, 5.63–13.09; P P P P =0.034). Conclusions: The fatal impact of bleeding and MI persisted beyond one year. Additional bleeding or MIs resulted in a poorer prognosis. De-escalation of antiplatelet therapy at the time of BARC 3 bleeding could have a major safety merit. These results emphasize the importance of considering the net clinical benefit including ischemic and bleeding events. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01813435.

Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154–6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.

Aims: The aim of this study was the external validation of the updated logistic clinical SYNTAX score for two-year all-cause mortality after PCI in the GLOBAL LEADERS trial. Methods and results: The GLOBAL LEADERS trial was an investigator-initiated, prospective randomised, multicentre, open-label trial comparing two strategies of antiplatelet therapy in 15,991 patients undergoing PCI. As a predefined analysis, we studied the first 4,006 consecutive patients enrolled between July 2013 and April 2014 for whom the anatomic SYNTAX scores were calculated by an independent core lab. The updated logistic clinical SYNTAX score was available in 3,271 patients. Patients were divided into quintiles according to the score. The C-statistic of the updated logistic clinical SYNTAX score for twoyear all-cause mortality was 0.71 (95% confidence interval [CI]: 0.64-0.77). The updated logistic clinical SYNTAX score identified patients at very high risk for two-year all-cause mortality after PCI. Although it systematically overestimated two-year all-cause mortality, predicted and observed two-year all-cause mortality in the majority of the patients (four out of five quintiles) were in agreement. Conclusions: Overall discrimination for two-year all-cause mortality of the updated logistic clinical SYNTAX score is either borderline acceptable or possibly helpful. Calibration in the majority of patients is appropriate. The score is potentially useful in selecting enriched high-risk populations.

Background ACEF score has been shown to have predictive ability in the patients undergoing percutaneous coronary intervention (PCI). The ACEF II score has recently been developed to predict short-term mortality after cardiac surgery. We compared the predictive ability of the ACEF and ACEF II scores to predict mortality after PCI in the all-comers population. Methods The ACEF and ACEF II scores were calculated in 15,968 patients enrolled in the GLOBAL LEADERS study. Discrimination and calibration were assessed for outcomes after PCI. Recalibration of the regression model by updating the intercept and slope were performed to adjust the original ACEF model to the PCI setting. In a stratified approach, patients were divided into quintiles according to the score. Outcomes were compared between quintiles. Results The ACEF and ACEF II score were available in 14,941 and 14,355 patients respectively. Discrimination for 30-day all-cause mortality was acceptable for both scores (C-statistic ACEF 0.75 and ACEF II 0.77). For 2-year all-cause mortality, the discrimination of ACEF score was acceptable (C-statistic 0.72) while the discrimination of ACEF II score was moderate (C-statistic 0.69). Both scores identified patients at high risk of mortality but overestimated all-cause mortality at 30 days in all quintiles. After recalibration, agreement between predicted and observed 30-day all-cause mortality in both scores are close to the identity line. Conclusions The ACEF II model did not improve the predictive ability of the ACEF score. Recalibrated ACEF model can be used to estimated all-cause mortality rate at 30 days after PCI.

IntroductionThe GLOBAL LEADERS is an open-label, pragmatic and superiority randomised controlled trial designed to challenge the current treatment paradigm of dual antiplatelet therapy (DAPT) for 12 months followed by aspirin monotherapy among patients undergoing percutaneous coronary intervention. By design, all study endpoints are investigator reported (IR) and not subject to formal adjudication by an independent Clinical Event Committee (CEC), which may introduce detection, reporting or ascertainment bias.Methods and analysisWe designed the GLOBAL LEADERS Adjudication Sub-StudY (GLASSY) to prospectively implement, in a large sample of patients enrolled within the GLOBAL LEADERS trial (7585 of 15 991, 47.5%), an independent adjudication process of reported and unreported potential endpoints, using standardised CEC procedures, in order to assess whether 23-month ticagrelor monotherapy (90 mg twice daily) after 1-month DAPT is non-inferior to a standard regimen of DAPT for 12 months followed by aspirin monotherapy for the primary efficacy endpoint of death, non-fatal myocardial infarction, non-fatal stroke or urgent target vessel revascularisation and superior for the primary safety endpoint of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium criteria.This study will comprehensively assess the comparative safety and efficacy of the two tested antithrombotic strategies on CEC-adjudicated ischaemic and bleeding endpoints and will provide insights into the role of a standardised CEC adjudication process on the interpretation of study findings by quantifying the level of concordance between IR-reported and CEC-adjudicated events.Ethics and disseminationGLASSY has been approved by local ethics committee of all study sites and/or by the central ethics committee for the country depending on country-specific regulations. In all cases, they deemed that it was not necessary to obtain further informed consent from individual subjects.Trial registration numberNCT01813435.

To determine (1) the medium-term effect of rosiglitazone and glipizide on intra-stent neointima hyperplasia, (2) restenosis pattern as assessed by intra-vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) in patients with T2DM and coronary artery disease. A total of 462 patients with T2DM were randomized to rosiglitazone or glipizide for up to 18 months in the APPROACH trial, and had evaluable baseline and follow-up IVUS examinations. There was no significant difference in the size of plaque behind stent between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (-5.6 mm(3) vs. 1.9 mm(3); P = 0.61) or with a drug-eluting stent (12.1 mm(3) vs. 5.5 mm(3); P = 0.09). Similarly, there was no significant difference in percentage intimal hyperplasia volume between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (24.1% vs. 19.8%; P = 0.38) or with a drug-eluting stent (9.8% vs. 8.3%; P = 0.57). QCA data (intra-stent late loss, intra-stent diameter stenosis or binary restenosis) were not different between the rosiglitazone and glipizide groups. This study suggests that both rosiglitazone and glipizide have a similar effect on neointimal growth at medium term follow-up, a finding that warrants investigation in dedicated randomized trials.

Background: The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods and results: The SXscore was prospectively collected M 1,397 of the 1,707 patients enrolled in the "all-comers" LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow 16 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; Cl 1.21-1.74; p

Aims: To investigate whether the use of intravascular ultrasound virtual histology (IVUS-VH) leads to any improvements in stent deployment, when performed in patients considered to have had an optimal percutaneous coronary intervention (PCI) by quantitative coronary angiography (QCA). Methods and results: After optimal PCI result (residual stenosis by QCA

Aims: Novolimus, a macrocyclic lactone with anti-proliferative properties, has a similar efficacy to currently available agents; however it requires a lower dose, and less polymer, and is therefore conceivably safer. Methods and results: The EXCELLA II study was a prospective, multicentre, single-blind, non-inferiority clinical trial which randomised 210 patients with a maximum of two de novo coronary artery lesions in two different epicardial vessels in a ratio of 2:1 to treatment with either the Elixir DESyne Novolimus Eluting Coronary Stent System (NES n=139, Elixir Medical, Sunnyvale, CA, USA) or the Endeavor zotarolimus eluting stent (ZES n=71, Medtronic, Santa Rosa, CA, USA). The primary endpoint was in-stent mean late lumen loss (LLL) at 9-months follow-up. In-stent percent volume obstruction (%VO) was measured in a sub-group of 65 patients having 9-month intravascular ultrasound (IVUS) follow-up. Clinical secondary endpoints included a device orientated composite of cardiac death, target vessel myocardial infarction (MI), and clinically indicated target lesion revascularisation (CI-TLR) assessed at 9-months follow-up. At 9-months, the in-stent LLL was 0.11±0.32 mm in the NES arm, as compared to 0.63±0.42 mm in the ZES (p