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Aims: Lipoprotein(a) concentration is associated with first cardiovascular events in clinical trials. It is unknown if this relationship holds for total (first and subsequent) events. In the ODYSSEY OUTCOMES trial in patients with recent acute coronary syndrome (ACS), the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab reduced lipoprotein(a), low-density lipoprotein cholesterol (LDL-C), and cardiovascular events compared with placebo. This post hoc analysis determined whether baseline levels and alirocumab-induced changes in lipoprotein(a) and LDL-C [corrected for lipoprotein(a) cholesterol] independently predicted total cardiovascular events., Methods and Results: Cardiovascular events included cardiovascular death, non-fatal myocardial infarction, stroke, hospitalization for unstable angina or heart failure, ischaemia-driven coronary revascularization, peripheral artery disease events, and venous thromboembolism. Proportional hazards models estimated relationships between baseline lipoprotein(a) and total cardiovascular events in the placebo group, effects of alirocumab treatment on total cardiovascular events by baseline lipoprotein(a), and relationships between lipoprotein(a) reduction with alirocumab and subsequent risk of total cardiovascular events. Baseline lipoprotein(a) predicted total cardiovascular events with placebo, while higher baseline lipoprotein(a) levels were associated with greater reduction in total cardiovascular events with alirocumab (hazard ratio Ptrend = 0.045). Alirocumab-induced reductions in lipoprotein(a) (median -5.0 [-13.6, 0] mg/dL) and corrected LDL-C (median -51.3 [-67.1, -34.0] mg/dL) independently predicted lower risk of total cardiovascular events. Each 5-mg/dL reduction in lipoprotein(a) predicted a 2.5% relative reduction in cardiovascular events., Conclusion: Baseline lipoprotein(a) predicted the risk of total cardiovascular events and risk reduction by alirocumab. Lipoprotein(a) lowering contributed independently to cardiovascular event reduction, supporting the concept of lipoprotein(a) as a treatment target after ACS., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Streamflow duration is used to differentiate reaches into discrete classes (e.g., perennial, intermittent, and ephemeral) for water resource management. Because the depiction of the extent and flow duration of streams via existing maps, remote sensing, and gauging is constrained, field-based tools are needed for use by practitioners and to validate hydrography and modeling advances. Streamflow Duration Assessment Methods (SDAMs) are rapid, reach-scale indices or models that use physical and biological indicators to predict flow duration class. We review the scientific basis for indicators and present conceptual and operational frameworks for SDAM development. Indicators can be responses to or controls of flow duration. Aquatic and terrestrial responses can be integrated into SDAMs, reflecting concurrent increases and decreases along the flow duration gradient. The conceptual framework for data-driven SDAM development shows interrelationships among the key components: study reaches, hydrologic data, and indicators. We present a generalized operational framework for SDAM development that integrates the data-driven components through five process steps: preparation, data collection, data analysis, evaluation, and implementation. We highlight priorities for the advancement of SDAMs, including expansion of gauging of nonperennial reaches, use of citizen science data, adjusting for stressor gradients, and statistical and monitoring advances to improve indicator effectiveness., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Concerns about the external validity of traditional randomized clinical trials (RCTs), together with the widespread availability of real-world data and advanced data analytic tools, have led to claims that common sense and clinical observation, rather than RCTs, should be the preferred method to generate evidence to support clinical decision-making. However, over the past 4 decades, results from well-done RCTs have repeatedly contradicted practices supported by common sense and clinical observation. Common sense and clinical observation fail for several reasons: incomplete understanding of pathophysiology, biases and unmeasured confounding in observational research, and failure to understand risks and benefits of treatments within complex systems. Concerns about traditional RCT models are legitimate, but randomization remains a critical tool to understand the causal relationship between treatments and outcomes. Instead, development and promulgation of tools to apply randomization to real-world data are needed to build the best evidence base in cardiovascular medicine., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The long-term prognostic impact of post-discharge bleeding in the unique population of patients with acute coronary syndrome (ACS) treated without percutaneous coronary intervention (PCI) remains unexplored., Objectives: The aim of this study was to assess the association between post-discharge bleeding and subsequent mortality after ACS according to index strategy (PCI or no PCI) and to contrast with the association between post-discharge myocardial infarction (MI) and subsequent mortality., Methods: In a harmonized dataset of 4 multicenter randomized trials (APPRAISE-2 [Apixaban for Prevention of Acute Ischemic Events-2], PLATO [Study of Platelet Inhibition and Patient Outcomes], TRACER [Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome], and TRILOGY ACS [Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes]), the association between post-discharge noncoronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate, severe, or life-threatening bleeding (landmark 7 days post-ACS) and subsequent all-cause mortality was evaluated in a time-updated Cox proportional hazards analysis. Interaction with index treatment strategy was assessed. Results were contrasted with risk for mortality following post-discharge MI., Results: Among 45,011 participants, 1,133 experienced post-discharge bleeding events (2.6 per 100 patient-years), and 2,149 died during follow-up. The risk for mortality was significantly higher <30 days (adjusted hazard ratio: 15.7; 95% confidence interval: 12.3 to 20.0) and 30 days to 12 months (adjusted hazard ratio: 2.7; 95% confidence interval: 2.1 to 3.4) after bleeding, and this association was consistent in participants treated with or without PCI for their index ACS (p for interaction = 0.240). The time-related association between post-discharge bleeding and mortality was similar to the association between MI and subsequent mortality in participants treated with and without PCI (p for interaction = 0.696)., Conclusions: Post-discharge bleeding after ACS is associated with a similar increase in subsequent all-cause mortality in participants treated with or without PCI and has an equivalent prognostic impact as post-discharge MI., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients with stable coronary heart disease, it is not known whether achievement of standard of care (SOC) targets in addition to evidence-based medicine (EBM) is associated with lower major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, and stroke., Methods: EBM use was recommended in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY trial. SOC targets were blood pressure (BP) <140/90 mm Hg and low-density lipoprotein-cholesterol (LDL-C) <100 mg/dL and <70 mg/dL. In patients with diabetes, glycosylated hemoglobin A1c (HbA1c) < 7% and BP of <130/80 mm Hg were recommended. Feedback to investigators about rates of EBM and SOC was provided regularly., Results: In 13,623 patients, 1-year landmark analysis assessed the association between EBM, SOC targets, and MACE during follow-up of 2.7 years (median) after adjustment in a Cox proportional hazards model. At 1 year, aspirin was prescribed in 92.5% of patients, statins in 97.2%, β-blockers in 79.0%, and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers in 76.9%. MACE was lower with LDL-C < 100 mg/dL (70-99 mg/dL) compared with LDL-C ≥ 100 mg/dL (hazard ratio [HR] 0.694, 95% CI 0.594-0.811) and lower with LDL-C < 70 mg/dL compared with LDL-C < 100 mg/dL (70-99 mg/dL) (HR 0.834, 95% CI 0.708-0.983). MACE was lower with HbA1c < 7% compared with HbA1c ≥ 7% (HR 0.705, 95% CI 0.573-0.866). There was no effect of BP targets on MACE., Conclusions: MACE was lower with LDL-C < 100 mg/dL (70-99 mg/dL) and even lower with LDL-C < 70 mg/dL. MACE in patients with diabetes was lower with HbA1c < 7%. Achievement of targets is associated with improved patient outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: There are concerns that price promotions encourage unhealthy dietary choices. This review aims to answer the following research questions (RQ1) what is the prevalence of price promotions on foods in high-income settings, and (RQ2) are price promotions more likely to be found on unhealthy foods?, Design: Systematic review of articles published in English, in peer-review journals, after 1 January 2000., Setting: Included studies measured the prevalence of price promotions (i.e. percentage of foods carrying a price promotion out of the total number of foods available to purchase) in retail settings, in upper-mid to high-income countries., Participants: 'Price promotion' was defined as a consumer-facing temporary price reduction or discount available to all customers. The control group/comparator was the equivalent products without promotions. The primary outcome for this review was the prevalence of price promotions, and the secondary outcome was the difference between the proportions of price promotions on healthy and unhealthy foods., Results: Nine studies (239 344 observations) were included for the meta-analysis for RQ1, the prevalence of price promotions ranged from 6 % (95 % CI 2 %, 15 %) for energy-dense nutrient-poor foods to 15 % (95 % CI 9 %, 25 %) for cereals, grains, breads and other starchy carbohydrates. However, the I-squared statistic was 99 % suggesting a very high level of heterogeneity. Four studies were included for the analysis of RQ2, of which two supported the hypothesis that price promotions were more likely to be found on unhealthy foods., Conclusions: The prevalence of price promotions is very context specific, and any proposed regulations should be supported by studies conducted within the proposed setting(s).

Importance: Although leadership behavior of physician supervisors is associated with the occupational well-being of the physicians they supervise, the factors associated with leadership behaviors are poorly understood., Objective: To evaluate the associations between burnout, professional fulfillment, and self-care practices of physician leaders and their independently assessed leadership behavior scores., Design, Setting, and Participants: This survey study of physicians and physician leaders at Stanford University School of Medicine (n = 1924) was conducted from April 1 to May 13, 2019. The survey included assessments of professional fulfillment, self-valuation, sleep-related impairment, and burnout. Physicians also rated the leadership behaviors of their immediate physician supervisors using a standardized assessment. Leaders' personal well-being metrics were paired with their leadership behavior scores as rated by the physicians they supervised. All assessment scores were converted to a standardized scale (range, 0-10). Data were analyzed from October 20, 2019, to March 10, 2020., Main Outcomes and Measures: Association between leaders' own well-being scores and their independently assessed leadership behavior., Results: Of 1924 physicians invited to participate, 1285 (66.8%) returned surveys, including 67 of 117 physician leaders (57.3%). Among these respondents, 651 (50.7%) were women and 729 (56.7%) were 40 years or older. Among the 67 leaders, 57 (85.1%) had their leadership behaviors evaluated by at least 5 physicians (median, 11 [interquartile range, 9-15]) they supervised. Overall, 9.8% of the variation in leaders' aggregate leadership behavior scores was associated with their own degree of burnout. In models adjusted for age and sex, each 1-point increase in burnout score of the leaders was associated with a 0.19-point decrement in leadership behavior score (β = -0.19; 95% CI, -0.35 to -0.03; P = .02), whereas each 1-point increase in their professional fulfillment and self-valuation scores was associated with a 0.13-point (β = 0.13; 95% CI, 0.01-0.26; P = .03) and 0.15-point (β = 0.15; 95% CI, 0.02-0.29; P = .03) increase in leadership behavior score, respectively. Each 1-point increase in leaders' sleep-related impairment was associated with a 0.15-point increment in sleep-related impairment among those they supervised (β = 0.15; 95% CI, 0.02-0.29; P = .03). The associations between leaders' well-being scores in other dimensions and the corresponding well-being measures of those they supervised were not significant., Conclusions and Relevance: In this survey study, burnout, professional fulfillment, and self-care practices of physician leaders were associated with their independently assessed leadership effectiveness. Training, skill building, and support to improve leader well-being should be considered a dimension of leadership development rather than simply a dimension of self-care.

Background: Cholesterol reduction with proprotein convertase subtilisin-kexin type 9 inhibitors reduces ischemic events; however, the cost-effectiveness in statin-treated patients with recent acute coronary syndrome remains uncertain., Objectives: This study sought to determine whether further cholesterol reduction with alirocumab would be cost-effective in patients with a recent acute coronary syndrome on optimal statin therapy., Methods: A cost-effectiveness model leveraging patient-level data from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was developed to estimate costs and outcomes over a lifetime horizon. Patients (n = 18,924) had a recent acute coronary syndrome and were on high-intensity or maximum-tolerated statin therapy, with a baseline low-density lipoprotein cholesterol (LDL-C) level ≥70 mg/dl, non-high-density lipoprotein cholesterol ≥100 mg/dl, or apolipoprotein B ≥80 mg/l. Alirocumab 75 mg or placebo was administered subcutaneously every 2 weeks. Alirocumab was blindly titrated to 150 mg if LDL-C remained ≥50 mg/dl or switched to placebo if 2 consecutive LDL-C levels were <15 mg/dl. Incremental cost per quality-adjusted life-year (QALY) was determined with the addition of alirocumab versus placebo and, based on clinical efficacy findings from the trial, was stratified by baseline LDL-C levels ≥100 mg/dl and <100 mg/dl., Results: Across the overall population recruited to the ODYSSEY OUTCOMES trial, using an annual treatment cost of US$5,850, the mean overall incremental cost-effectiveness ratio was US$92,200 per QALY (base case). The cost was US$41,800 per QALY in patients with baseline LDL-C ≥100 mg/dl, whereas in those with LDL-C <100 mg/dl the cost per QALY was US$299,400. Among patients with LDL-C ≥100 mg/dl, incremental cost-effectiveness ratios remained below US$100,000 per QALY across a wide variety of sensitivity analyses., Conclusions: In patients with a recent acute coronary syndrome on optimal statin therapy, alirocumab improves cardiovascular outcomes at costs considered intermediate value, with good value in patients with baseline LDL-C ≥100 mg/dl but less economic value with LDL-C <100 mg/dl. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Determining the right dosage of aspirin for the secondary prevention treatment of atherosclerotic cardiovascular disease (ASCVD) remains an unanswered and critical question., Objective: To report the rationale and design for a randomized clinical trial to determine the optimal dosage of aspirin to be used for secondary prevention of ASCVD, using an innovative research method., Design, Setting, and Participants: This pragmatic, open-label, patient-centered, randomized clinical trial is being conducted in 15 000 patients within the National Patient-Centered Clinical Research Network (PCORnet), a distributed research network of partners including clinical research networks, health plan research networks, and patient-powered research networks across the United States. Patients with established ASCVD treated in routine clinical practice within the network are eligible. Patient recruitment began in April 2016. Enrollment was completed in June 2019. Final follow-up is expected to be completed by June 2020., Interventions: Participants are randomized on a web platform in a 1:1 fashion to either 81 mg or 325 mg of aspirin daily., Main Outcomes and Measures: The primary efficacy end point is the composite of all-cause mortality, hospitalization for nonfatal myocardial infarction, or hospitalization for a nonfatal stroke. The primary safety end point is hospitalization for major bleeding associated with a blood-product transfusion. End points are captured through regular queries of the health systems' common data model within the structure of PCORnet's distributed data environment., Conclusions and Relevance: As a pragmatic study and the first interventional trial conducted within the PCORnet electronic data infrastructure, this trial is testing several unique and innovative operational approaches that have the potential to disrupt and transform the conduct of future patient-centered randomized clinical trials by evaluating treatments integrated in clinical practice while at the same time determining the optimal dosage of aspirin for secondary prevention of ASCVD., Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain., Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction., Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32)., Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.)., (Copyright © 2020 Massachusetts Medical Society.)

Accurate assessment of cardiac function is crucial for the diagnosis of cardiovascular disease 1 , screening for cardiotoxicity 2 and decisions regarding the clinical management of patients with a critical illness 3 . However, human assessment of cardiac function focuses on a limited sampling of cardiac cycles and has considerable inter-observer variability despite years of training 4,5 . Here, to overcome this challenge, we present a video-based deep learning algorithm-EchoNet-Dynamic-that surpasses the performance of human experts in the critical tasks of segmenting the left ventricle, estimating ejection fraction and assessing cardiomyopathy. Trained on echocardiogram videos, our model accurately segments the left ventricle with a Dice similarity coefficient of 0.92, predicts ejection fraction with a mean absolute error of 4.1% and reliably classifies heart failure with reduced ejection fraction (area under the curve of 0.97). In an external dataset from another healthcare system, EchoNet-Dynamic predicts the ejection fraction with a mean absolute error of 6.0% and classifies heart failure with reduced ejection fraction with an area under the curve of 0.96. Prospective evaluation with repeated human measurements confirms that the model has variance that is comparable to or less than that of human experts. By leveraging information across multiple cardiac cycles, our model can rapidly identify subtle changes in ejection fraction, is more reproducible than human evaluation and lays the foundation for precise diagnosis of cardiovascular disease in real time. As a resource to promote further innovation, we also make publicly available a large dataset of 10,030 annotated echocardiogram videos.

Problem/condition: Autism spectrum disorder (ASD)., Period Covered: 2016., Description of System: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition., Results: For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months)., Interpretation: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children., Public Health Action: These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Zachary Warren reports personal fees from Hoffman La Roche, grants and personal fees from Adaptive Technology Consulting, grants from Autism Speaks, grants from Cognoa, and grants from Simons Foundation; all fees and grants received are outside the submitted work. John Constantino reports a grant from Western Psychological Services outside the submitted work.

The mission of the American Heart Association is to be a relentless force for a world of longer, healthier lives. The American Heart Association has consistently prioritized the needs and perspective of the patient in taking positions on healthcare reform while recognizing the importance of biomedical research, providers, and healthcare delivery systems in advancing the care of patients and the prevention of disease. The American Heart Association's vision for healthcare reform describes the foundational changes needed for the health system to serve the best interests of patients and to achieve health care and coverage that are adequate, accessible, and affordable for everyone living in the United States. The American Heart Association is committed to advancing the dialogue around healthcare reform and has prepared this updated statement of our principles, placed in the context of the advances in coverage and care that have occurred after the passage of the Affordable Care Act, the rapidly changing landscape of healthcare delivery systems, and our evolving recognition that efforts to prevent cardiovascular disease can have synergistic benefit in preventing other diseases and improving overall well-being. These updated principles focus on expanding access to affordable health care and coverage; enhancing the availability of evidence-based preventive services; eliminating disparities that limit the availability and equitable delivery of health care; strengthening the public health infrastructure to respond to social determinants of health; prioritizing and accelerating investments in biomedical research; and growing a diverse, culturally competent health and healthcare workforce prepared to meet the challenges of delivering high-value health care.

Understanding and addressing the unique health needs of people residing in rural America is critical to the American Heart Association's pursuit of a world with longer, healthier lives. Improving the health of rural populations is consistent with the American Heart Association's commitment to health equity and its focus on social determinants of health to reduce and ideally to eliminate health disparities. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders to make rural populations a priority in programming, research, and policy. This advisory first summarizes existing data on rural populations, communities, and health outcomes; explores 3 major groups of factors underlying urban-rural disparities in health outcomes, including individual factors, social determinants of health, and health delivery system factors; and then proposes a set of solutions spanning health system innovation, policy, and research aimed at improving rural health.

Background: Dietary sugar, especially in liquid form, increases risk of dental caries, adiposity, and type 2 diabetes. The United Kingdom Soft Drinks Industry Levy (SDIL) was announced in March 2016 and implemented in April 2018 and charges manufacturers and importers at £0.24 per litre for drinks with over 8 g sugar per 100 mL (high levy category), £0.18 per litre for drinks with 5 to 8 g sugar per 100 mL (low levy category), and no charge for drinks with less than 5 g sugar per 100 mL (no levy category). Fruit juices and milk-based drinks are exempt. We measured the impact of the SDIL on price, product size, number of soft drinks on the marketplace, and the proportion of drinks over the lower levy threshold of 5 g sugar per 100 mL., Methods and Findings: We analysed data on a total of 209,637 observations of soft drinks over 85 time points between September 2015 and February 2019, collected from the websites of the leading supermarkets in the UK. The data set was structured as a repeat cross-sectional study. We used controlled interrupted time series to assess the impact of the SDIL on changes in level and slope for the 4 outcome variables. Equivalent models were run for potentially levy-eligible drink categories ('intervention' drinks) and levy-exempt fruit juices and milk-based drinks ('control' drinks). Observed results were compared with counterfactual scenarios based on extrapolation of pre-SDIL trends. We found that in February 2019, the proportion of intervention drinks over the lower levy sugar threshold had fallen by 33.8 percentage points (95% CI: 33.3-34.4, p < 0.001). The price of intervention drinks in the high levy category had risen by £0.075 (£0.037-0.115, p < 0.001) per litre-a 31% pass through rate-whilst prices of intervention drinks in the low levy category and no levy category had fallen and risen by smaller amounts, respectively. Whilst the product size of branded high levy and low levy drinks barely changed after implementation of the SDIL (-7 mL [-23 to 11 mL] and 16 mL [6-27ml], respectively), there were large changes to product size of own-brand drinks with an increase of 172 mL (133-214 mL) for high levy drinks and a decrease of 141 mL (111-170 mL) for low levy drinks. The number of available drinks that were in the high levy category when the SDIL was announced was reduced by 3 (-6 to 12) by the implementation of the SDIL. Equivalent models for control drinks provided little evidence of impact of the SDIL. These results are not sales weighted, so do not give an account of how sugar consumption from drinks may have changed over the time period., Conclusions: The results suggest that the SDIL incentivised many manufacturers to reduce sugar in soft drinks. Some of the cost of the levy to manufacturers and importers was passed on to consumers as higher prices but not always on targeted drinks. These changes could reduce population exposure to liquid sugars and associated health risks., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: ADMB and MW are members of the Faculty of Public Health, which has a position statement supporting a soft drink tax. AMDB is also a former member of the UK Health Forum, which had a position statement supporting soft drink taxes. ADMB has written various peer-reviewed and commissioned papers on soft drink taxes. MR is chair of Sustain: the alliance for better food and farming, which has for more than eight years campaigned for a sugary drinks tax in the UK. MW receives salary as Director of NIHR's Public Health Research Progamme, outside the submitted work.

Echocardiography uses ultrasound technology to capture high temporal and spatial resolution images of the heart and surrounding structures, and is the most common imaging modality in cardiovascular medicine. Using convolutional neural networks on a large new dataset, we show that deep learning applied to echocardiography can identify local cardiac structures, estimate cardiac function, and predict systemic phenotypes that modify cardiovascular risk but not readily identifiable to human interpretation. Our deep learning model, EchoNet, accurately identified the presence of pacemaker leads (AUC = 0.89), enlarged left atrium (AUC = 0.86), left ventricular hypertrophy (AUC = 0.75), left ventricular end systolic and diastolic volumes ( R 2  = 0.74 and R 2  = 0.70), and ejection fraction ( R 2  = 0.50), as well as predicted systemic phenotypes of age ( R 2  = 0.46), sex (AUC = 0.88), weight ( R 2  = 0.56), and height ( R 2  = 0.33). Interpretation analysis validates that EchoNet shows appropriate attention to key cardiac structures when performing human-explainable tasks and highlights hypothesis-generating regions of interest when predicting systemic phenotypes difficult for human interpretation. Machine learning on echocardiography images can streamline repetitive tasks in the clinical workflow, provide preliminary interpretation in areas with insufficient qualified cardiologists, and predict phenotypes challenging for human evaluation., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2020.)

Background: The identification of acutely ill patients at high risk for venous thromboembolism (VTE) may be determined clinically or by use of integer-based scoring systems. These scores demonstrated modest performance in external data sets., Objectives: To evaluate the performance of machine learning models compared to the IMPROVE score., Methods: The APEX trial randomized 7513 acutely medically ill patients to extended duration betrixaban vs. enoxaparin. Including 68 variables, a super learner model (ML) was built to predict VTE by combining estimates from 5 families of candidate models. A "reduced" model (rML) was also developed using 16 variables that were thought, a priori, to be associated with VTE. The IMPROVE score was calculated for each patient. Model performance was assessed by discrimination and calibration to predict a composite VTE end point. The frequency of predicted risks of VTE were plotted and divided into tertiles. VTE risks were compared across tertiles., Results: The ML and rML algorithms outperformed the IMPROVE score in predicting VTE (c-statistic: 0.69, 0.68 and 0.59, respectively). The Hosmer-Lemeshow goodness-of-fit P -value was 0.06 for ML, 0.44 for rML, and <0.001 for the IMPROVE score. The observed event rate in the lowest tertile was 2.5%, 4.8% in tertile 2, and 11.4% in the highest tertile. Patients in the highest tertile of VTE risk had a 5-fold increase in odds of VTE compared to the lowest tertile., Conclusion: The super learner algorithms improved discrimination and calibration compared to the IMPROVE score for predicting VTE in acute medically ill patients., (© 2020 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.)

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C)., Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE)., Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina., Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081)., Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The consumption of free sugars in the UK is more than double the guideline intake for adults and close to triple for children, with soft drinks representing a significant proportion. The aim of this study was to assess how individual soft drink companies and consumers have responded to calls to reduce sugar consumption, including the soft drink industry levy (SDIL), between 2015 and 2018., Methods: This was an annual cross-sectional study using nutrient composition data of 7377 products collected online, paired with volume sales data for 195 brands offered by 57 companies. The main outcome measures were sales volume, sugar content and volume of sugars sold by company and category, expressed in total and per capita per day terms., Results: Between 2015 and 2018, the volume of sugars sold per capita per day from soft drinks declined by 30%, equivalent to a reduction of 4.6 g per capita per day. The sales-weighted mean sugar content of soft drinks fell from 4.4 g/100 ml in 2015 to 2.9 g/100 ml in 2018. The total volume sales of soft drinks that are subject to the SDIL (i.e. contain more than 5 g/100 ml of sugar) fell by 50%, while volume sales of low- and zero-sugar (< 5 g/100 ml) drinks rose by 40%., Conclusion: Action by the soft drinks industry to reduce sugar in products and change their product portfolios, coupled with changes in consumer purchasing, has led to a significant reduction in the total volume and per capita sales of sugars sold in soft drinks in the UK. The rate of change accelerated between 2017 and 2018, which also implies that the implementation of the SDIL acted as an extra incentive for companies to reformulate above and beyond what was already being done as part of voluntary commitments to reformulation, or changes in sales driven by consumer preferences.

Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non-high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor., Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category., Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; P interaction =0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; P interaction =0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; P interaction =0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; P interaction =0.661)., Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402.

Background: Smartphone apps might enable interventions to increase physical activity, but few randomised trials testing this hypothesis have been done. The MyHeart Counts Cardiovascular Health Study is a longitudinal smartphone-based study with the aim of elucidating the determinants of cardiovascular health. We aimed to investigate the effect of four different physical activity coaching interventions on daily step count in a substudy of the MyHeart Counts Study., Methods: In this randomised, controlled crossover trial, we recruited adults (aged ≥18 years) in the USA with access to an iPhone smartphone (Apple, Cupertino, CA, USA; version 5S or newer) who had downloaded the MyHeart Counts app (version 2.0). After completion of a 1 week baseline period of interaction with the MyHeart Counts app, participants were randomly assigned to receive one of 24 permutations (four combinations of four 7 day interventions) in a crossover design using a random number generator built into the app. Interventions consisted of either daily prompts to complete 10 000 steps, hourly prompts to stand following 1 h of sitting, instructions to read the guidelines from the American Heart Association website, or e-coaching based upon the individual's personal activity patterns from the baseline week of data collection. Participants completed the trial in a free-living setting. Due to the nature of the interventions, participants could not be masked from the intervention. Investigators were not masked to intervention allocation. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in the modified intention-to-treat analysis set, which included all participants who had completed 7 days of baseline monitoring and at least 1 day of one of the four interventions. This trial is registered with ClinicalTrials.gov, NCT03090321., Findings: Between Dec 12, 2016, and June 6, 2018, 2783 participants consented to enrol in the coaching study, of whom 1075 completed 7 days of baseline monitoring and at least 1 day of one of the four interventions and thus were included in the modified intention-to-treat analysis set. 493 individuals completed the full set of assigned interventions. All four interventions significantly increased mean daily step count from baseline (mean daily step count 2914 [SE 74]): mean step count increased by 319 steps (75) for participants in the American Heart Association website prompt group (p<0·0001), 267 steps (74) for participants in the hourly stand prompt group (p=0·0003), 254 steps (74) for participants in the cluster-specific prompts group (p=0·0006), and by 226 steps (75) for participants in the 10 000 daily step prompt group (p=0·0026 vs baseline)., Interpretation: Four smartphone-based physical activity coaching interventions significantly increased daily physical activity. These findings suggests that digital interventions delivered via a mobile app have the ability to increase short-term physical activity levels in a free-living cohort., Funding: Stanford Data Science Initiative., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Importance: Multiple states publicly report a hospital's risk-adjusted mortality rate for percutaneous coronary intervention (PCI) as a quality measure. However, whether reported annual PCI mortality is associated with a hospital's future performance is unclear., Objective: To evaluate the association between reported risk-adjusted hospital PCI-related mortality and a hospital's future PCI-related mortality., Design, Setting, and Participants: This study used data from the New York Percutaneous Intervention Reporting System from January 1, 1998, to December 31, 2016, to assess hospitals that perform PCI., Exposures: Public-reported, risk-adjusted, 30-day mortality after PCI., Main Outcomes and Measures: The primary analysis evaluated the association between a hospital's reported risk-adjusted PCI-related mortality and future PCI-related mortality. The correlation between a hospital's observed to expected (O/E) PCI-related mortality rates each year and future O/E mortality ratios was assessed. Multivariable linear regression was used to examine the association between index year O/E mortality and O/E mortality in subsequent years while adjusting for PCI volume and patient severity., Results: This study included 67 New York hospitals and 960 hospital-years. Hospitals with low PCI-related mortality (O/E mortality ratio, ≤1) and high mortality (O/E mortality ratio, >1) had inverse associations between their O/E mortality ratio in the index year and the subsequent change in the ratio (hospitals with low mortality, r = -0.45; hospitals with high mortality, r = -0.60). Little of the variation in risk-adjusted mortality was explained by prior performance. An increase in the O/E mortality ratio from 1.0 to 2.0 in the index year was associated with a higher O/E mortality ratio of only 0.15 (95% CI, 0.02-0.27) in the following year., Conclusions and Relevance: At hospitals with high or low PCI-related mortality rates, the rates largely regressed to the mean the following year. A hospital's risk-adjusted mortality rate was poorly associated with its future mortality. The annual hospital PCI-related mortality may not be a reliable factor associated with hospital quality to consider in a practice change or when helping patients select high-quality hospitals.

Background: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear., Methods: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria., Results: A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02)., Conclusions: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor., Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population)., Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8-3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74-0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction =0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78-1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75-1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48-2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36-3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74-1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75-0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction =0·012. Benefit was present irrespective of time from most recent PCI., Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk., Funding: AstraZeneca., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aspirin is the cornerstone of the antithrombotic management of patients with established atherosclerotic cardiovascular disease, but major guidelines provide conflicting recommendations for its use in primary prevention. Findings from recent randomized trials totaling >47 000 patients called into question the net clinical benefits of aspirin in primary prevention for 3 key populations: patients with diabetes mellitus, community-dwelling elderly individuals, and patients without diabetes mellitus who are at intermediate risk for atherosclerotic events. In the context of increasing emphasis on the use of other treatments for primary prevention in patients with moderate-high future risk of developing atherosclerotic cardiovascular disease, the efficacy and safety of aspirin for primary prevention has become uncertain. Key unresolved questions regarding the role of aspirin in primary prevention include the optimal drug formulation, dosing schedule, weight-based dose selection, and interplay between sex and treatment response. In the current era, most patients without established atherosclerotic cardiovascular disease should not be prescribed aspirin. Rather, aggressive management of comorbidities tailored to the expected cardiovascular risk needs to be emphasized. In this context, informed shared decision making between clinicians and patients regarding the use of aspirin for primary prevention of cardiovascular events is a suitable and laudable approach. In this article, we revisit the role of aspirin for the primary prevention of cardiovascular diseases by critically reviewing the key scientific literature, highlight key areas of uncertainties for future research, and propose a decisional framework for clinicians to support prescription of aspirin in primary prevention.

Monitoring and managing resident workload is a cornerstone of policy in graduate medical education, and the duty hours metric is the backbone of current regulations. While the duty hours metric measures hours worked, it does not capture differences in intensity of work completed during those hours, which may independently contribute to fatigue and burnout. Few such metrics exist. Digital data streams generated during the usual course of hospital operations can serve as a novel source of insight into workload intensity by providing high-resolution, minute-by-minute data at the individual level; however, study and use of these data streams for workload monitoring has been limited to date. Paging data is one such data stream. In this work, we analyze over 500,000 pages-two full years of pages in an academic internal medicine residency program-to characterize paging patterns among housestaff. We demonstrate technical feasibility, validity, and utility of paging burden as a metric to provide insight into resident workload beyond duty hours alone, and illustrate a general framework for evaluation and incorporation of novel digital data streams into resident workload monitoring., Competing Interests: Competing interestsThe authors declare no competing interests.

Background: Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined., Objectives: This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy., Methods: Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint., Results: Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: -2.4% to 6.2%), and 13.0% (95% CI: -2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: -0.1% to 1.0%), 1.3% (95% CI: -1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%)., Conclusions: In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with a recent acute coronary syndrome (ACS) receiving oral antiplatelets and anticoagulants are at risk for bleeding and subsequent adverse non-bleeding-related events., Methods: In this post hoc analysis, we evaluated 7,392 high-risk patients (median follow-up 241 days) with a recent ACS randomized to apixaban or placebo in APPRAISE-2. Clinical events during a 30-day period after Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding were analyzed using unadjusted and adjusted Cox proportional-hazards models., Results: In total, 153 (2.1%) patients experienced TIMI major/minor bleeding during follow-up. Bleeding risk for patients on triple therapy (apixaban, thienopyridine, and aspirin) was increased compared with those on dual therapy (apixaban plus aspirin: hazard ratio [HR] 2.02, 95% CI 1.08-3.79; thienopyridine plus aspirin: HR 1.99, 95% CI 1.41-2.83). Those receiving apixaban/aspirin had similar bleeding risk compared with those receiving thienopyridine/aspirin (HR 1.01, 95% CI 0.53-1.95). Patients who experienced TIMI major/minor bleeding had an increased risk of 30-day all-cause mortality (HR 24.7, 95% CI 15.34-39.66) and ischemic events (HR 6.7, 95% CI 3.14-14.14)., Conclusions: In a contemporary cohort of high-risk patients after ACS, bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic or anticoagulant strategy. Patients receiving apixaban plus aspirin had a similar bleeding risk compared with those receiving thienopyridine plus aspirin. Interventions to improve outcomes in patients after ACS should include strategies to optimize the reduction in ischemic events while minimizing the risk of bleeding., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin-kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI., Methods and Results: Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77-0.99; P = 0.032) and Type 2 (0.77, 0.61-0.97; P = 0.025), but not Type 4 MI., Conclusion: After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The intravenous, rapidly acting P2Y12 inhibitor cangrelor reduces the rate of ischemic events during PCI with no significant increase in severe bleeding. However, the efficacy and safety of cangrelor compared with clopidogrel in patients treated with single vessel (SV)-percutaneous coronary intervention (PCI) or multivessel (MV)-PCI remains unexplored., Methods: We studied the modified intention-to-treat population of patients from the CHAMPION PHOENIX trial who were randomized to either cangrelor or clopidogrel. We used logistic regression and propensity score matching to evaluate the effect of cangrelor compared with clopidogrel on the primary efficacy outcome (composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis) at 48 hours. The safety outcome was moderate or severe Global Utilization of Streptokinase and tPA for Occluded Arteries bleeding at 48 hours., Hypothesis: Cangrelor is as efficacious and safe as clopidogrel in both SV and MV PCI., Results: Among 10 854 patients, 9204 (85%) underwent SV- and 1650 (15%) MV-PCI. After adjustment, cangrelor was associated with similar reductions vs clopidogrel in the primary efficacy outcome in patients undergoing SV-PCI (4.5% vs 5.2%; odds ratio [OR] 0.81 [0.66-0.98]) or MV-PCI (6.1% vs 9.8%, OR 0.59 [0.41-0.85]; Pint 0.14). Similar results were observed after propensity score matching (SV-PCI: 5.5% vs 5.9%, OR 0.93 [0.74-1.18]; MV-PCI: 6.2% vs 8.9%, OR 0.67 [0.44-1.01]; Pint 0.17). There was no evidence of heterogeneity in the treatment effect of cangrelor compared with clopidogrel for the safety outcome., Conclusions: In patients undergoing SV- or MV-PCI, cangrelor was associated with similar relative risk reductions in ischemic complications and no increased risk of significant bleeding compared with clopidogrel, which highlights the expanding repertoire of options for use in complex PCI., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)