Publications by authors named "Marco Valgimigli"

571 Publications

Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After PCI: An Individual Patient-Level Meta-Analysis.

JACC Cardiovasc Interv 2021 Feb;14(4):444-456

Applied Health Research Centre of the Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.

Objectives: The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents.

Background: The role of abbreviated DAPT followed by an oral P2Y inhibitor after PCI remains uncertain.

Methods: Two randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO (CRD42019143120). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale.

Results: Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval [CI]: 0.41 to 0.75; p < 0.001). The composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT (HR: 0.92; 95% CI: 0.76 to 1.10; p < 0.001 for noninferiority). Ticagrelor was associated with lower risk for all-cause (HR: 0.71; 95% CI: 0.52 to 0.96; p = 0.027) and cardiovascular (HR: 0.68; 95% CI: 0.47 to 0.99; p = 0.044) mortality. Rates of myocardial infarction (2.01% vs. 2.05%; p = 0.88), stent thrombosis (0.29% vs. 0.38%; p = 0.32), and stroke (0.47% vs. 0.36%; p = 0.30) were similar.

Conclusions: Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.
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http://dx.doi.org/10.1016/j.jcin.2020.11.046DOI Listing
February 2021

Access-Site Crossover in Patients With Acute Coronary Syndrome Undergoing Invasive Management.

JACC Cardiovasc Interv 2021 Feb;14(4):361-373

Department of Cardiology, Inselspital, University of Bern, Bern, Switzerland; Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland. Electronic address:

Objectives: The aim of this study was to assess the impact of access-site crossover in patients with acute coronary syndrome undergoing invasive management via radial or femoral access.

Background: There are limited data on the clinical implications of access-site crossover.

Methods: In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox)-Access trial, 8,404 patients with acute coronary syndrome were randomized to radial or femoral access. Patients undergoing access-site crossover or successful access site were investigated. Thirty-day coprimary outcomes were a composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and a composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding (net adverse clinical events [NACE]).

Results: Access-site crossover occurred in 183 of 4,197 patients (4.4%) in the radial group (mainly to femoral access) and 108 of 4,207 patients (2.6%) in the femoral group (mainly to radial access). In multivariate analysis, the risk for coprimary outcomes was not significantly higher with radial crossover compared with successful radial (MACE: adjusted rate ratio [adjRR]: 1.25; 95% confidence interval [CI]: 0.81 to 1.93; p = 0.32; NACE: adjRR: 1.40; 95% CI: 0.94 to 2.06; p = 0.094) or successful femoral access (MACE: adjRR: 1.17; 95% CI: 0.76 to 1.81; p = 0.47; NACE: adjRR: 1.26; 95% CI: 0.86 to 1.86; p = 0.24). Access site-related Bleeding Academic Research Consortium type 3 or 5 bleeding was higher with radial crossover than successful radial access. Femoral crossover remained associated with higher risks for MACE (adjRR: 1.84; 95% CI: 1.18 to 2.87; p = 0.007) and NACE (adjRR: 1.69; 95% CI: 1.09 to 2.62; p = 0.019) compared with successful femoral access. Results remained consistent after excluding patients with randomized access not attempted.

Conclusions: Crossover from radial to femoral access abolishes the bleeding benefit offered by the radial over femoral artery but does not appear to increase the risk for MACE or NACE compared with successful radial or femoral access. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627).
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http://dx.doi.org/10.1016/j.jcin.2020.11.042DOI Listing
February 2021

Predicting 2-year all-cause mortality after contemporary PCI: Updating the logistic clinical SYNTAX score.

Catheter Cardiovasc Interv 2021 Feb 4. Epub 2021 Feb 4.

Department of Cardiology, National University of Ireland Galway, Galway, Ireland.

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.
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http://dx.doi.org/10.1002/ccd.29490DOI Listing
February 2021

Comparison of Investigator-Reported and Clinical Event Committee-Adjudicated Outcome Events in GLASSY.

Circ Cardiovasc Qual Outcomes 2021 Feb 4;14(2):e006581. Epub 2021 Feb 4.

Department of Cardiology, Cardiocentro Ticino, Lugano, Switzerland (M. Valgimigli).

Background: Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events.

Methods: We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers.

Results: Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak.

Conclusions: Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.006581DOI Listing
February 2021

Patient-tailored antithrombotic therapy following percutaneous coronary intervention.

Eur Heart J 2021 Jan 29. Epub 2021 Jan 29.

Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y12 inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing , and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.
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http://dx.doi.org/10.1093/eurheartj/ehaa1097DOI Listing
January 2021

Prognostic Implications of Declining Hemoglobin Content in Patients Hospitalized With Acute Coronary Syndromes.

J Am Coll Cardiol 2021 Feb;77(4):375-388

Department of Cardiology, Inselspital, University of Bern, Bern, Switzerland; Cardiocentro Ticino, Lugano, Switzerland. Electronic address:

Background: Contemporary definitions of bleeding endpoints are restricted mostly to clinically overt events. Whether hemoglobin drop per se, with or without overt bleeding, adversely affects the prognosis of patients with acute coronary syndrome (ACS) remains unclear.

Objectives: The aim of this study was to examine in the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial the incidence, predictors, and prognostic implications of in-hospital hemoglobin drop in patients with ACS managed invasively stratified by the presence of in-hospital bleeding.

Methods: Patients were categorized by the presence and amount of in-hospital hemoglobin drop on the basis of baseline and nadir hemoglobin values and further stratified by the occurrence of adjudicated in-hospital bleeding. Hemoglobin drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl). Using multivariate Cox regression, we modeled the association between hemoglobin drop and mortality in patients with and without overt bleeding.

Results: Among 7,781 patients alive 24 h after randomization with available hemoglobin data, 6,504 patients (83.6%) had hemoglobin drop, of whom 5,756 (88.5%) did not have overt bleeding and 748 (11.5%) had overt bleeding. Among patients without overt bleeding, minor (hazard ratio [HR]: 2.37; 95% confidence interval [CI]: 1.32 to 4.24; p = 0.004) and major (HR: 2.58; 95% CI: 0.98 to 6.78; p = 0.054) hemoglobin drop were independently associated with higher 1-year mortality. Among patients with overt bleeding, the association of minor and major hemoglobin drop with 1-year mortality was directionally similar but had wider CIs (minor: HR: 3.53 [95% CI: 1.06 to 11.79]; major: HR: 13.32 [95% CI: 3.01 to 58.98]).

Conclusions: Among patients with ACS managed invasively, in-hospital hemoglobin drop ≥3 g/dl, even in the absence of overt bleeding, is common and is independently associated with increased risk for 1-year mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; NCT01433627).
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http://dx.doi.org/10.1016/j.jacc.2020.11.046DOI Listing
February 2021

European position paper on the management of patients with patent foramen ovale. Part II - Decompression sickness, migraine, arterial deoxygenation syndromes and select high-risk clinical conditions.

Eur Heart J 2021 Jan 28. Epub 2021 Jan 28.

Newcastle University and Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom.

Patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions but to date only one official position paper related to left circulation thromboembolism has been published. This interdisciplinary paper, prepared with the involvement of eight European scientific societies, reviews the available evidence and proposes a rationale for decision making for other PFO-related clinical conditions. In order to guarantee a strict evidence-based process, we used a modified grading of recommendations, assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements were weighed and graded according to predefined scales. Despite being based on limited and observational or low-certainty randomised data, a number of position statements were made to frame PFO management in different clinical settings, along with suggestions for new research avenues. This interdisciplinary position paper, recognising the low or very low certainty of existing evidence, provides the first approach to several PFO-related clinical scenarios beyond left circulation thromboembolism and strongly stresses the need for fresh high-quality evidence on these topics.
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http://dx.doi.org/10.1093/eurheartj/ehaa1070DOI Listing
January 2021

Composition, structure, and function of heart teams: a joint position paper of the ACVC, EAPCI, EACTS, and EACTA focused on the management of patients with complex coronary artery disease requiring myocardial revascularization.

Eur J Cardiothorac Surg 2021 Jan 18. Epub 2021 Jan 18.

Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.

Contemporary cardiovascular medicine is complex, dynamic, and interactive. Therefore, multidisciplinary dialogue between different specialists is required to deliver optimal and patient-centred care. This has led to the concept of explicit collaborations of different specialists caring for patients with complex cardiovascular diseases-that is 'heart teams'. These teams are particularly valuable to minimize referral bias and improve guideline adherence as so to be responsive to patient preferences, needs, and values but may be challenging to coordinate, especially in the acute setting. This position paper-jointly developed by four cardiovascular associations-is intended to provide conceptual and practical considerations for the composition, structure, and function of multidisciplinary teams. It focuses on patients with complex coronary artery diseases in both elective and urgent setting and provide guidance on how to implement the heart team both in chronic and in acute coronary syndromes patients, including cases with mechanical complications and haemodynamic instability; it also discusses strategies for clear and transparent patient communication and provision of a patient-centric approach. Finally, gaps in evidence and research perspectives in this context are discussed.
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http://dx.doi.org/10.1093/ejcts/ezaa402DOI Listing
January 2021

Assessing the Risks of Bleeding vs Thrombotic Events in Patients at High Bleeding Risk After Coronary Stent Implantation: The ARC-High Bleeding Risk Trade-off Model.

JAMA Cardiol 2021 Jan 6. Epub 2021 Jan 6.

London School of Hygiene and Tropical Medicine, London, United Kingdom.

Importance: Patients who are candidates for percutaneous coronary intervention (PCI) and are at high bleeding risk constitute a therapeutic challenge because they often also face an increased risk of thrombotic complications.

Objectives: To develop and validate models to predict the risks of major bleeding (Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and myocardial infarction (MI) and/or stent thrombosis (ST) for individual patients at high bleeding risk and provide assistance in defining procedural strategy and antithrombotic regimens.

Design, Setting, And Participants: This prognostic study used individual patient data from 6 studies conducted from July 1, 2009, to September 5, 2017, for 6641 patients at more than 200 centers in Europe, the US, and Asia who underwent PCI and were identified as being at high bleeding risk using the Academic Research Consortium criteria. In 1 year of follow-up (excluding periprocedural events), individual patient risks of MI and/or ST and major bleeding were evaluated using 33 baseline variables. To validate these models, a subgroup of 1458 patients at high bleeding risk from the ONYX ONE trial were analyzed. Statistical analysis was performed from February 1, 2019, to April 30, 2020.

Exposures: All patients underwent PCI with bare metal, drug-coated, or drug-eluting stent implants.

Main Outcomes And Measures: Forward, stepwise multivariable proportional hazards models were used to identify highly significant predictors of MI and/or ST and BARC types 3 to 5 bleeding.

Results: A total of 6641 patients (4384 men [66.0%]; median age, 77.9 years [interquartile range, 70.0-82.6 years]) were included in this study. Over 365 days, nonperiprocedural MI and/or ST occurred in 350 patients (5.3%), and BARC types 3 to 5 bleeding occurred in 381 patients (5.7%). Eight independent baseline predictors of risk of MI and/or ST and 8 predictors for risk of BARC types 3 to 5 bleeding were identified. Four of these predictors were in both risk models. Both risk models showed moderate discrimination: C statistic = 0.69 for predicting MI and/or ST and 0.68 for predicting BARC types 3 to 5 bleeding. Applying these same models to the validation cohort gave a similar strength of discrimination (C statistic = 0.74 for both MI and/or ST and BARC types 3-5 bleeding). Patients with MI and/or ST had a mortality hazard ratio of 6.1 (95% CI, 4.8-7.7), and those with BARC types 3 to 5 bleeding had a mortality hazard ratio of 3.7 (95% CI, 2.9-4.8) compared with patients free of both events. Taking these data into account, the risk scores facilitate investigation of the individual patient trade-off between these 2 risks: 2931 patients (44.1%) at high bleeding risk in the 6 studies had a greater risk of MI and/or ST than of BARC 3 to 5 bleeding, 1555 patients (23.4%) had a greater risk of BARC 3 to 5 bleeding than of MI and/or ST, and 2155 (32.4%) had a comparable risk of both events.

Conclusions And Relevance: In a large cohort of patients at high bleeding risk undergoing PCI, 2 prognostic models have been developed to identify individual patients' risk of major coronary thrombotic and bleeding events. In future clinical practice, using an application on a smartphone to evaluate the trade-off between these 2 quantifiable risks for each patient may help clinicians choose the most appropriate revascularization strategy and tailor the duration and intensity of antithrombotic regimens.
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http://dx.doi.org/10.1001/jamacardio.2020.6814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788509PMC
January 2021

The impact of the COVID-19 pandemic upon patients, staff, and on the future practices of percutaneous coronary intervention.

Eur Heart J Suppl 2020 Dec 23;22(Suppl Pt t):P13-P18. Epub 2020 Dec 23.

Department of Cardiology, Inselspital Universitätsspital, Bern Freiburgstrasse 4, Bern 3010, Switzerland.

The COVID pandemic in 2020 had unpredictable consequences on the presentation and management of patients with ischaemic heart disease. Subsequent to these initial responses the impact of the initial pandemic can be reviewed and responses can be considered. It is clear that there are new opportunities for optimising patient management pathways and in particular enhanced use of information technology. Changes in attitudes towards health and perceived risk are evident within both the catheter lab teams and our patient cohorts. Summating both the intellectual and emotional experiences of the pandemic are essential to prepare for either a second wave of COVID 19 or any new pandemic threat in the future.
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http://dx.doi.org/10.1093/eurheartj/suaa171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757716PMC
December 2020

Sex differences in distribution, management and outcomes of combined ischemic-bleeding risk following acute coronary syndrome.

Int J Cardiol 2020 Dec 31. Epub 2020 Dec 31.

Keele Cardiovascular Research Group, Institutes of Applied Clinical Science and Primary Care and Health Sciences, Keele University, Stoke-on-Trent, United Kingdom; Department of Cardiology, Royal Stoke Hospital, University Hospital North Midlands, Stoke-on-Trent, United Kingdom.

Background: Risk factors for further bleeding and ischemic events after acute coronary syndrome (ACS) often overlap. Little is known about sex-based differences in the management and outcomes of ACS patients according to their combined bleeding-ischemic risk.

Methods: All ACS hospitalizations in the United Kingdom (2010-2017) were retrospectively analyzed, stratified by sex and bleeding-ischemic risk combination (using CRUSADE and GRACE scores). Multivariable logistic regression was performed to examine association between risk-groups and 1) receipt of guideline-recommended management and 2) in-hospital outcomes.

Results: Of 584,360 patients, a third of males (32.3%) and females (32.6%) were in the dual high-risk group (High CRUSADE- High GRACE). In comparison to the dual low-risk group (Low CRUSADE-Low GRACE), the dual high-risk patients of both sexes were 59-83% less likely to receive inpatient revascularisation (PCI or CABG) and 50% less likely to receive dual antiplatelet therapy (DAPT) on discharge, with a significant increase in odds of MACE (~8 to 9-fold), all-cause and cardiac mortality (25 to 35-fold), and bleeding (78-91%). The greatest difference in management and clinical outcomes between sexes was found in the dual-high risk group where females were less likely to receive guideline-recommended therapy (revascularisation and DAPT), compared to males, and were more likely to experience MACE, all-cause and cardiac mortality.

Conclusion: ACS patients with dual high-risk for bleeding and recurrent ischemia, especially females, are less likely to receive guideline-recommended therapy and experience significantly worse outcomes. Novel strategies are needed to effectively manage this highly prevalent, complex patient group and address the under-treatment of females.
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http://dx.doi.org/10.1016/j.ijcard.2020.12.063DOI Listing
December 2020

Comparing methods for estimating patient-specific treatment effects in individual patient data meta-analysis.

Stat Med 2021 Mar 27;40(6):1553-1573. Epub 2020 Dec 27.

Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

Meta-analysis of individual patient data (IPD) is increasingly used to synthesize data from multiple trials. IPD meta-analysis offers several advantages over meta-analyzing aggregate data, including the capacity to individualize treatment recommendations. Trials usually collect information on many patient characteristics. Some of these covariates may strongly interact with treatment (and thus be associated with treatment effect modification) while others may have little effect. It is currently unclear whether a systematic approach to the selection of treatment-covariate interactions in an IPD meta-analysis can lead to better estimates of patient-specific treatment effects. We aimed to answer this question by comparing in simulations the standard approach to IPD meta-analysis (no variable selection, all treatment-covariate interactions included in the model) with six alternative methods: stepwise regression, and five regression methods that perform shrinkage on treatment-covariate interactions, that is, least absolute shrinkage and selection operator (LASSO), ridge, adaptive LASSO, Bayesian LASSO, and stochastic search variable selection. Exploring a range of scenarios, we found that shrinkage methods performed well for both continuous and dichotomous outcomes, for a variety of settings. In most scenarios, these methods gave lower mean squared error of the patient-specific treatment effect as compared with the standard approach and stepwise regression. We illustrate the application of these methods in two datasets from cardiology and psychiatry. We recommend that future IPD meta-analysis that aim to estimate patient-specific treatment effects using multiple effect modifiers should use shrinkage methods, whereas stepwise regression should be avoided.
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http://dx.doi.org/10.1002/sim.8859DOI Listing
March 2021

Validation and Additive Predictive Value of the Academic Research Consortium-High Bleeding Risk Criteria in Older Adults.

Thromb Haemost 2020 Dec 22. Epub 2020 Dec 22.

Department of Molecular Cardiology, University of Pavia, Pavia, Italy.

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http://dx.doi.org/10.1055/a-1342-3750DOI Listing
December 2020

Effects of Fentanyl Versus Morphine on Ticagrelor-Induced Platelet Inhibition in Patients With ST-Segment Elevation Myocardial Infarction: The PERSEUS Randomized Trial.

Circulation 2020 Dec 21;142(25):2479-2481. Epub 2020 Dec 21.

Department of Cardiology, Geneva University Hospitals, Switzerland (J.F.I., S.D.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.049287DOI Listing
December 2020

The multiplication of loaves and fishes approach: A Critic to Double anti-thrombotics or to Double number of ischemic events?

Eur Heart J Cardiovasc Pharmacother 2020 Dec 19. Epub 2020 Dec 19.

CardioCentro Ticino, Via Tesserete 48, Lugano, Switzerland.

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http://dx.doi.org/10.1093/ehjcvp/pvaa141DOI Listing
December 2020

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

J Am Coll Cardiol 2020 12;76(25):2982-3021

Icahn School of Medicine at Mount Sinai, New York, New York, USA; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
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http://dx.doi.org/10.1016/j.jacc.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755038PMC
December 2020

Short dual antiplatelet therapy followed by P2Y12 inhibitor monotherapy vs. prolonged dual antiplatelet therapy after percutaneous coronary intervention with second-generation drug-eluting stents: a systematic review and meta-analysis of randomized clinical trials.

Eur Heart J 2021 Jan;42(4):308-319

Department of Cardiac-Thoracic-Vascular Sciences, University of Padova, Via Giustiniani 2, 35128 Padua, Italy.

Aims: After percutaneous coronary intervention (PCI) with second-generation drug-eluting stent (DES), whether short dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with a P2Y12 receptor inhibitor confers benefits compared with prolonged DAPT is unclear.

Methods And Results: Multiple electronic databases, including PubMed, Scopus, Web of Sciences, Ovid, and ScienceDirect, were searched to identify randomized clinical trials comparing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT after PCI with second-generation DES implantation. The primary and co-primary outcomes of interest were major bleeding and stent thrombosis 1 year after randomization. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fixed-effect and random-effects models. Multiple sensitivity analyses including random-effects models 95% CI adjustment were applied. A sensitivity analysis comparing trials using P2Y12 inhibitor SAPT with those using aspirin SAPT was performed. A total of five randomized clinical trials (32 145 patients) were available. Major bleeding was significantly lower in the patients assigned to short DAPT followed by P2Y12 inhibitor SAPT compared with those assigned to 12-month DAPT (random-effects model: HR 0.63, 95% 0.45-0.86). No significant differences between groups were observed in terms of stent thrombosis (random-effects model: HR 1.19, 95% CI 0.86-1.65) and the secondary endpoints of all-cause death (random-effects model: HR 0.85, 95% CI 0.70-1.03), myocardial infarction (random-effects model: HR 1.05, 95% CI 0.89-1.23), and stroke (random-effects model: HR 1.08, 95% CI 0.68-1.74). Sensitivity analyses showed overall consistent results. By comparing trials testing ≤3 months of DAPT followed by P2Y12 inhibitor SAPT vs. 12 months of DAPT with trials testing ≤3 months of DAPT followed by aspirin SAPT vs. 12-month of DAPT, there was no treatment-by-subgroup interaction for each endpoint. By combining all these trials, regardless of the type of SAPT, short DAPT was associated with lower major bleeding (random-effects model: HR 0.63, 95% CI 0.48-0.83) and no differences in stent thrombosis, all-cause death, myocardial infarction, and stroke were observed between regimens.

Conclusion: After second-generation DES implantation, 1-3 months of DAPT followed by P2Y12 inhibitor SAPT is associated with lower major bleeding and similar stent thrombosis, all-cause death, myocardial infarction, and stroke compared with prolonged DAPT. Whether P2Y12 inhibitor SAPT is preferable to aspirin SAPT needs further investigation.
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http://dx.doi.org/10.1093/eurheartj/ehaa739DOI Listing
January 2021

Bleeding risk prediction in elderly patients managed invasively for acute coronary syndromes: External validation of the PRECISE-DAPT and PARIS scores.

Int J Cardiol 2021 Apr 3;328:22-28. Epub 2020 Dec 3.

University of Pavia, Pavia, Italy.

Background: We sought to assess and compare the prediction power of the PRECISE-DAPT and PARIS risk scores with regards to bleeding events in elderly patients suffering from acute coronary syndromes (ACS) and undergoing invasive management.

Methods: Our external validation cohort included 1883 patients older >74 years admitted for ACS and treated with PCI from 3 prospective, multicenter trials.

Results: After a median follow-up of 365 days, patients in the high-risk categories according to the PRECISE-DAPT score experienced a higher rate of BARC 3-5 bleedings (p = 0.002) while this was not observed for those in the high-risk category according to the PARIS risk score (p = 0.3). Both scores had a moderate discriminative power (c-statistics 0.70 and 0.64, respectively) and calibration was accurate for both risk scores (all χ > 0.05), but PARIS risk score was associated to a greater overestimation of the risk (p = 0.02). Decision curve analysis was in favor of the PRECISE-DAPT score up to a risk threshold of 2%.

Conclusions: In the setting of older adults managed invasively for ACS both the PARIS and the PRECISE-DAPT scores were moderately accurate in predicting bleeding risk. However, the use of the PRECISE-DAPT is associated with better performance.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.065DOI Listing
April 2021

Antithrombotic therapy according to baseline bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention: applying the PRECISE-DAPT score in RE-DUAL PCI.

Eur Heart J Cardiovasc Pharmacother 2020 Dec 1. Epub 2020 Dec 1.

Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA.

Aims: Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg bid, clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT.

Methods And Results: A score ≥25 points qualified high bleeding-risk (HBR). Comparisons were made for the primary safety endpoint ISTH major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thromboembolic events, or unplanned revascularization, analyzed by time-to-event analysis. PRECISE-DAPT was available in 2,336/2,725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR (HR 0.42, 95%CI, 0.31-0.57) and HBR (HR 0.70, 95%CI, 0.52-0.94), with a greater magnitude of benefit among non-HBR (Pint=0.02). DAT with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95%CI, 0.45-0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95%CI, 0.63-1.34, Pint=0.08). Risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint=0.45 and Pint=0.56, respectively).

Conclusions: PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications, and may help clinicians identifying the antithrombotic regimen intensity with the best benefit-risk ratio in an individual patient.
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http://dx.doi.org/10.1093/ehjcvp/pvaa135DOI Listing
December 2020

Impact of optical coherence tomography findings on clinical outcomes in ST-segment elevation myocardial infarction patients: a MATRIX (Minimizing Adverse Hemorrhagic Events by Trans-radial Access Site and angioX) OCT sub-study.

Int J Cardiovasc Imaging 2020 Nov 22. Epub 2020 Nov 22.

Swiss Cardiovascular Center, University of Bern, Bern, Switzerland.

Purpose: To investigate the association of the degree of stent expansion, as assessed by optical coherence tomography (OCT), following stent implantation, and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients.

Methods: STEMI patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) OCT study were selected; Clinical outcomes were collected through 1 year. Stent expansion index is a minimum stent area (MSA) divided by average lumen area (average of proximal and distal reference lumen area). The following variables were measured: MSA (< 4.5mm), dissection (> 200 µm in width and < 5 mm from stent segment), malapposition (> 200 µm distance of stent from vessel wall), a thrombus (area > 5% of lumen area) were compared.

Results: A total of 151 patients were included; after excluding patients with suboptimal OCT quality, the population with available OCT was classified into 2 groups: under-expanded < 90% (N = 72, 51%) and well-expanded ≥ 90% (N = 67, 49%). In the well-expanded group, a significant number of the proximal vessels had a lumen area < 4.5mm (16.1%, p < 0.001) and a greater thrombus burden within stent (56.7%, p = 0.042). The overall 30 day and 1 year major adverse cardiovascular event (MACE) rates were 5% and 6.1%, respectively.

Conclusion: Irrespective of the degree of stent expansion, the OCT findings, in STEMI patients, and the MACE at 30 days and one year follow up was low; further, well-expanded stents led to a more significant residual thrombotic burden within the stent but seemed to have insignificant clinical impact. Acknowledged stent optimization criteria, traditionally related to worse outcomes in stable patients, do not seem to be associated with worse outcomes in this STEMI population.
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http://dx.doi.org/10.1007/s10554-020-02098-8DOI Listing
November 2020

Usefulness of updated logistic clinical SYNTAX score based on MI-SYNTAX score in patients with ST-elevation myocardial infarction.

Catheter Cardiovasc Interv 2020 Nov 11. Epub 2020 Nov 11.

Department of Cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland.

Objectives: To compare the predictive performances of the prewiring, postwiring MI-SYNTAX scores, prewiring, and postwiring Updated Logistic Clinical SYNTAX score (LCSS) for 2-year all-cause mortality post percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients.

Background: In patients with STEMI and undergoing primary PCI, coronary stenosis(es) distal to the culprit lesion is often observed after the restoration of coronary flow. To address comprehensively the complex coronary anatomy in these patients, prewiring and postwiring MI-SYNTAX scores have been reported in the literature. Furthermore, to enable individualized risk estimation for long-term all-cause mortality, the Updated LCSS has been developed by combining the anatomical SYNTAX score and clinical factors.

Methods: In the randomized GLOBAL LEADERS trial, anatomical SYNTAX score analysis was performed by an independent angiographic corelab for the first 4,000 consecutive patients as a prespecified analysis; of these, 545 presented with STEMI. The efficacy of the mortality predictions of the four scores at 2 years were evaluated based on their discrimination and calibration abilities.

Results: Complete data was available in 512 patients (93.9%). When the patients were stratified into two groups based on the median of the scores, the prewiring and postwiring Updated LCSSs demonstrated that the high-score groups were associated with higher rates of 2-year all-cause mortality compared to the low-score groups (6.6 vs. 1.2%; log-rank p = .001 and 6.6 vs. 1.2%; log-rank p = .001, respectively). There were no statistically significant differences for predicting the mortality between the prewiring (area under the curve [AUC] 0.625), postwiring MI-SYNTAX score (AUC 0.614), prewiring (AUC 0.755), and postwiring Updated LCSS (AUC 0.757). In the integrated discrimination improvement (IDI), the prewiring MI-SYNTAX score had a better discrimination for the mortality than the postwiring MI-SYNTAX score (IDI -0.0082; p = .029). The four scores had acceptable calibration abilities for 2-year all-cause mortality.

Conclusions: The prewiring Updated LCSS predicts long-term all-cause mortality with clearly useful discrimination and acceptable calibration. Since the postwiring MI-SYNTAX score does not improve mortality prediction, the prewiring MI-SYNTAX score may be preferred for the 2-year mortality prediction using the Updated LCSS.
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http://dx.doi.org/10.1002/ccd.29383DOI Listing
November 2020

Unravelling the puzzle of antithrombotic therapies for complex percutaneous coronary intervention.

Eur Heart J Cardiovasc Pharmacother 2020 Sep 16. Epub 2020 Sep 16.

Department of Cardiology, Bern University Hospital, Freiburgstrasse 18, 3010 Bern, Switzerland.

Percutaneous coronary intervention (PCI) has remarkably evolved in the last decades. This has resulted in a larger number of patients treated with PCI, including those with more complex anatomic lesions. Several studies demonstrated that PCI involving complex lesions is associated with increased rate of procedural complications and adverse clinical outcomes. In this setting, optimal adjunctive antithrombotic regimens still need to be defined. In this review, we sought to summarize and discuss the recent evidence deriving from analyses appraising antithrombotic therapies in patients undergoing complex PCI.
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http://dx.doi.org/10.1093/ehjcvp/pvaa107DOI Listing
September 2020

Discharge Location and Outcomes After Transcatheter Aortic Valve Implantation.

Am J Cardiol 2021 02 2;140:95-102. Epub 2020 Nov 2.

Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address:

The relation between discharge location and outcomes after transcatheter aortic valve implantation (TAVI) is largely unknown. Thus, the objective of this study was to investigate the impact of discharge location on clinical outcomes after TAVI. Between August 2007 and December 2018, consecutive patients who underwent transfemoral TAVI at Bern University Hospital were grouped according to discharge location. Clinical adverse events were adjudicated according to VARC-2 end point definitions. Of 1,902 eligible patients, 520 (27.3%) were discharged home, 945 (49.7%) were discharged to a rehabilitation clinic and 437 (23.0%) were transferred to another institution. Compared with patients discharged to a rehabilitation facility or another institution, patients discharged home were younger (80.8 ± 6.5 vs 82.9 ± 5.4 and 82.8 ± 6.4 years), less likely female (37.3% vs 59.7% and 54.2%), and at lower risk according to STS-PROM (4.5 ± 3.0% vs 5.5 ± 3.8% and 6.6 ± 4.4%). At 1 year follow-up, patients discharged home had similar rates of all-cause mortality (HR 0.82; 95% CI 0.54 to 1.24), cerebrovascular events (HR 1.04; 95% CI 0.52 to 2.08) and bleeding complications (HR 0.93; 95% CI 0.61 to 1.41) compared with patients discharged to a rehabilitation facility. Patients discharged home or to rehabilitation were at lower risk for death (HR 0.37; 95% CI 0.24 to 0.56 and HR 0.44; 95% CI 0.32 to 0.60) and bleeding (HR 0.48; 95% CI 0.30 to 0.76 and HR 0.66; 95% CI 0.45 to 0.96) during the first year after hospital discharge compared with patients transferred to another institution. In conclusion, discharge location is associated with outcomes after TAVI with patients discharged home or to a rehabilitation facility having better clinical outcomes than patients transferred to another institution. Clinical Trial Registration: https://www.clinicaltrials.gov. NCT01368250.
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http://dx.doi.org/10.1016/j.amjcard.2020.10.058DOI Listing
February 2021

Antithrombotic therapy in heart failure and sinus rhythm: the ongoing search for a better match of patients to therapy.

Eur J Heart Fail 2020 Nov 1. Epub 2020 Nov 1.

CardioCentro Ticino, Lugano and University of Bern, Bern, Switzerland.

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http://dx.doi.org/10.1002/ejhf.2045DOI Listing
November 2020

Safety and efficacy of double versus triple antithrombotic therapy in patients with atrial fibrillation with or without acute coronary syndrome undergoing percutaneous coronary intervention: a collaborative meta-analysis of NOAC-based randomized clinical trials.

Eur Heart J Cardiovasc Pharmacother 2020 Oct 29. Epub 2020 Oct 29.

Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Aims: Safety and efficacy of antithrombotic regimens in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) may differ based on clinical presentation. We sought to comparing double vs. triple antithrombotic therapy (DAT vs TAT) in AF patients with or without acute coronary syndrome (ACS) undergoing PCI.

Methods And Results: A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials. Data on subgroups of ACS or elective PCI were obtained by published reports or trial investigators. A total of 10,193 patients from 4 NOAC trials were analyzed, of whom 5,675 presenting with ACS (DAT = 3,063 vs. TAT = 2,612) and 4,518 with SCAD (DAT = 2,421 vs. TAT = 2,097). The primary safety endpoint of ISTH major bleeding or CRNMB was reduced with DAT compared with TAT in both ACS (12.2% vs 19.4%; RR 0.63, 95% CI 0.56-0.71; p < 0.0001; I2=0%) and SCAD (14.6% vs 22.0%; RR 0.68, 95% CI 0.55-0.85; p = 0.0008; I2=66%), without interaction (p-int = 0.54). Findings were consistent for secondary bleeding endpoints, including intracranial Haemorrhage. In both subgroups, there was no difference between DAT and TAT for all-cause death, major adverse cardiovascular events, or stroke. Myocardial infarction and stent thrombosis were numerically higher with DAT vs. TAT consistently in ACS and SCAD (p-int = 0.60 and 0.86 respectively). Findings were confirmed by multiple sensitivity analyses, including a separate analysis on dabigatran regimens and a restriction to PCI population.

Conclusions: DAT, compared with TAT, is associated with lower bleeding risks, including intracranial Haemorrhage, and a small non-significant excess of cardiac ischaemic events in both patients with or without ACS.
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http://dx.doi.org/10.1093/ehjcvp/pvaa116DOI Listing
October 2020

Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis.

Clin Res Cardiol 2020 Oct 24. Epub 2020 Oct 24.

Department of Cardiology and Intensive Care, Jessa Ziekenhuis, Faculty of Medicine and Life Sciences at the Hasselt University, Hasselt, Belgium.

Aims: This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHADS-VASc score parameters as predictors for clinical outcome.

Methods: Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis.

Results: Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHADS-VASc score was associated with increased rates of all outcomes. CHADS-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024).

Conclusion: After PCI in AF patients, increasing CHADS-VASc score was associated with increased bleeding rates and CHADS-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.
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http://dx.doi.org/10.1007/s00392-020-01760-4DOI Listing
October 2020

Ticagrelor monotherapy in patients with concomitant diabetes mellitus and chronic kidney disease: a post hoc analysis of the GLOBAL LEADERS trial.

Cardiovasc Diabetol 2020 10 16;19(1):179. Epub 2020 Oct 16.

Department of Cardiology, National University of Ireland Galway, Galway, Ireland.

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 < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55-0.99], p = 0.043, p = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56-0.99], p = 0.044, p = 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, p = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29-0.82], p = 0.007, p = 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).
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http://dx.doi.org/10.1186/s12933-020-01153-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568378PMC
October 2020

Safety and Efficacy of 1-Month Dual Antiplatelet Therapy (Ticagrelor + Aspirin) Followed by 23-Month Ticagrelor Monotherapy in Patients Undergoing Staged Percutaneous Coronary Intervention (A Sub-Study from GLOBAL LEADERS).

Am J Cardiol 2021 01 13;138:1-10. Epub 2020 Oct 13.

Department of Cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland; NHLI, Imperial College London, London, United Kingdom. Electronic address:

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.
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http://dx.doi.org/10.1016/j.amjcard.2020.09.057DOI Listing
January 2021

Comparative influence of bleeding and ischemic risk factors on diabetic patients undergoing percutaneous coronary intervention with everolimus-eluting stents.

Catheter Cardiovasc Interv 2020 Oct 10. Epub 2020 Oct 10.

The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York City, New York.

Objective: To investigate the impact of ischemic and bleeding risk factors on long-term clinical outcomes of patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) with everolimus-eluting stents.

Background: Second-generation drug-eluting stents have substantially improved outcomes after PCI in the general population; however, DM patients continue to experience high rates of ischemic and bleeding complications.

Methods: DM patients from the pooled XIENCE V registry were divided into high or low bleeding and ischemic risk groups (HBR, LBR, HIR, and LIR) based on established bleeding (age ≥ 75 years; chronic kidney disease; anemia; prior stroke; oral anticoagulation; thrombocytopenia; prior major bleeding) and ischemic (acute coronary syndrome; prior myocardial infarction [MI]; ≥3 stents implanted; ≥3 vessels treated; ≥3 lesions treated; stent length > 60 mm; bifurcation treated with ≥2 stents; chronic total occlusion) risk factors. The primary outcomes were major adverse cardiac events (MACE; cardiac death, MI, or stent thrombosis) and major bleeding at 4-year follow-up.

Results: A total of 3,704 DM patients were divided into four groups (21.5% LBR/LIR; 39.0% LBR/HIR; 15.6% HBR/LIR; 23.9% HBR/HIR). Compared with LBR/LIR patients, those at HBR/HIR and HBR/LIR had a significantly higher risk of MACE (HR (95% CI) 2.7 (1.9-3.9) and 2.2 (1.5-3.2), respectively) and major bleeding (2.7 (1.6-4.8) and 2.6 (1.4-4.7), respectively), while LBR/HIR patients did not.

Conclusions: Among DM patients undergoing PCI, presence of bleeding risk factors was associated with a higher risk of both ischemic and bleeding events, whereas commonly used features of ischemic risk did not impact long-term clinical outcomes.
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http://dx.doi.org/10.1002/ccd.29314DOI Listing
October 2020