Guidelines evaluate and summarize available evidence, with the aim of assisting health professionals in proposing the best diagnostic or therapeutic approach for an individual patient with a given condition. Guidelines are intended for use by health professionals and the European Society of Cardiology (ESC) makes its Guidelines freely available. ESC Guidelines do not override the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient or the patient’s caregiver where appropriate and/or necessary. It is also the health professional’s responsibility to verify the rules and regulations applicable in each country to drugs and devices at the time of prescription, and, where appropriate, to respect the ethical rules of their profession. ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated. ESC Policies and Procedures for formulating and issuing ESC Guidelines can be found on the ESC website (https://www.escardio.org/Guidelines). The Members of this Task Force were selected by the ESC to represent professionals involved with the medical care of patients with this pathology. The selection procedure aimed to include members from across the whole of the ESC region and from relevant ESC Subspecialty Communities. Consideration was given to diversity and inclusion, notably with respect to gender and country of origin. The Task Force performed a critical evaluation of diagnostic and therapeutic approaches, including assessment of the risk-benefit ratio. The strength of every recommendation and the level of evidence supporting them were weighed and scored according to pre-defined scales as outlined below. The Task Force followed ESC voting procedures, and all approved recommendations were subject to a vote and achieved at least 75% agreement among voting members. The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. Their declarations of interest were reviewed according to the ESC declaration of interest rules and can be found on the ESC website (http://www.escardio.org/Guidelines), and have been compiled in a report published in a supplementary document with the guidelines. The Task Force received its entire financial support from the ESC without any involvement from the healthcare industry. The ESC Clinical Practice Guidelines (CPG) Committee supervises and co-ordinates the preparation of new guidelines and is responsible for the approval process. ESC Guidelines undergo extensive review by the CPG Committee and external experts, including members from across the whole of the ESC region and from relevant ESC Subspecialty Communities and National Cardiac Societies. After appropriate revisions, the guidelines are signed off by all the experts involved in the Task Force. The finalized document is signed off by the CPG Committee for publication in the European Heart Journal. The guidelines were developed after careful consideration of the scientific and medical knowledge and the evidence available at the time of their writing. Tables of evidence summarizing the findings of studies informing development of the guidelines are included. The ESC warns readers that the technical language may be misinterpreted and declines any responsibility in this respect. Off-label use of medication may be presented in the current Guidelines if a sufficient level of evidence shows that it can be considered medically appropriate for a given condition. However, the final decisions concerning an individual patient must be made by the responsible health professional giving special consideration to: The specific situation of the patient. Unless otherwise provided for by national regulations, off-label use of medication should be limited to situations where it is in the patient’s interest with regard to the quality, safety, and efficacy of care, and only after the patient has been informed and has provided consent. Country-specific health regulations, indications by governmental drug regulatory agencies, and the ethical rules to which health professionals are subject, where applicable.
BACKGROUND: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. METHODS: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. FINDINGS: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. INTERPRETATION: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. FUNDING: Bill & Melinda Gates Foundation.
BACKGROUND AND PURPOSE: Population-wide reductions in cardiovascular disease incidence and mortality have not been shared equally by African Americans. The burden of cardiovascular disease in the African American community remains high and is a primary cause of disparities in life expectancy between African Americans and whites. The objectives of the present scientific statement are to describe cardiovascular health in African Americans and to highlight unique considerations for disease prevention and management. METHOD: The primary sources of information were identified with PubMed/Medline and online sources from the Centers for Disease Control and Prevention. RESULTS: The higher prevalence of traditional cardiovascular risk factors (eg, hypertension, diabetes mellitus, obesity, and atherosclerotic cardiovascular risk) underlies the relatively earlier age of onset of cardiovascular diseases among African Americans. Hypertension in particular is highly prevalent among African Americans and contributes directly to the notable disparities in stroke, heart failure, and peripheral artery disease among African Americans. Despite the availability of effective pharmacotherapies and indications for some tailored pharmacotherapies for African Americans (eg, heart failure medications), disease management is less effective among African Americans, yielding higher mortality. Explanations for these persistent disparities in cardiovascular disease are multifactorial and span from the individual level to the social environment. CONCLUSIONS: The strategies needed to promote equity in the cardiovascular health of African Americans require input from a broad set of stakeholders, including clinicians and researchers from across multiple disciplines.
Cardiovascular diseases are widespread among patients with chronic noncommunicable diseases and are one of the leading causes of death, including in the working age. The article presents the relevance of the development and application of patient-oriented systems, in which machine learning (ML) is a promising technology that allows predicting cardiovascular diseases. Automated machine learning (AutoML) makes it possible to simplify and speed up the process of developing AI/ML applications, which is key in the development of patient-oriented systems by application users, in particular medical specialists. The authors propose a framework for the application of automatic machine learning and three scenarios that allowed for data combining five data sets of cardiovascular disease indicators from the UCI Machine Learning Repository to investigate the effectiveness in detecting this class of diseases. The study investigated one AutoML model that used and optimized the hyperparameters of thirteen basic ML models (KNeighborsUnif, KNeighborsDist, LightGBMXT, LightGBM, RandomForestGini, RandomForestEntr, CatBoost, ExtraTreesGini, ExtraTreesEntr, NeuralNetFastA, XGBoost, NeuralNetTorch, Light
Background: Cardiovascular diseases (CVDs) are the leading cause of death globally. The use of artificial intelligence (AI) methods - in particular, deep learning (DL) - has been on the rise lately for the analysis of different CVD-related topics. The use of fundus images and optical coherence tomography angiography (OCTA) in the diagnosis of retinal diseases has also been extensively studied. To better understand heart function and anticipate changes based on microvascular characteristics and function, researchers are currently exploring the integration of AI with non-invasive retinal scanning. There is great potential to reduce the number of cardiovascular events and the financial strain on healthcare systems by utilizing AI-assisted early detection and prediction of cardiovascular diseases on a large scale. Method: A comprehensive search was conducted across various databases, including PubMed, Medline, Google Scholar, Scopus, Web of Sciences, IEEE Xplore, and ACM Digital Library, using specific keywords related to cardiovascular diseases and artificial intelligence. Results: The study included 87 English-language publications selected for relevance, and additional references we
Multimorbidity, the co-occurrence of two or more chronic diseases such as diabetes, obesity or cardiovascular diseases in one patient, is a frequent phenomenon. To make care more efficient, it is of relevance to understand how different diseases condition each other over the life time of a patient. However, most of our current knowledge on such patient careers is either confined to narrow time spans or specific (sets of) diseases. Here, we present a population-wide analysis of long-term patient trajectories by clustering them according to their disease history observed over 17 years. When patients acquire new diseases, their cluster assignment might change. A health trajectory can then be described by a temporal sequence of disease clusters. From the transitions between clusters we construct an age-dependent multilayer network of disease clusters. Random walks on this multilayer network provide a more precise model for the time evolution of multimorbid health states when compared to models that cluster patients based on single diseases. Our results can be used to identify decisive events that potentially determine the future disease trajectory of a patient. We find that for elderly
Cardiovascular diseases (CVD) are a predominant health concern globally, emphasizing the need for advanced diagnostic techniques. In our research, we present an avant-garde methodology that synergistically integrates ECG readings and retinal fundus images to facilitate the early disease tagging as well as triaging of the CVDs in the order of disease priority. Recognizing the intricate vascular network of the retina as a reflection of the cardiovascular system, alongwith the dynamic cardiac insights from ECG, we sought to provide a holistic diagnostic perspective. Initially, a Fast Fourier Transform (FFT) was applied to both the ECG and fundus images, transforming the data into the frequency domain. Subsequently, the Earth Mover's Distance (EMD) was computed for the frequency-domain features of both modalities. These EMD values were then concatenated, forming a comprehensive feature set that was fed into a Neural Network classifier. This approach, leveraging the FFT's spectral insights and EMD's capability to capture nuanced data differences, offers a robust representation for CVD classification. Preliminary tests yielded a commendable accuracy of 84 percent, underscoring the potent
Early detection of cancer and cardiovascular diseases is fundamental to improving patient outcomes and reducing healthcare expenditure. Current cancer screening programs are targeted towards specific cancers and are often inaccessible to large parts of the population, particularly in remote regions. This project aimed to develop digital blood twins: machine learning models that leverage routinely collected blood test data, demographics, comorbidities, and prescribed medications, for scalable and cost-effective disease screening. Digital blood twins were constructed using the UK Biobank dataset (n = 373,269). Using age, sex, comorbidities, medication profiles, and blood test z-scores, three iterations of XGBoost classifiers were trained for broad cancer, colorectal cancer, and cardiovascular disease prediction. Model interpretability was achieved through SHAP and dimensionality reduction analyses (UMAP, t-SNE). Broad-category cancer models achieved ROC-AUC = 0.607-0.706. Colorectal cancer prediction demonstrated excellent discrimination (ROC-AUC = 0.816-0.993), and cardiovascular models showed clinical utility, notably for hypertension (ROC-AUC = 0.813, F1 = 0.861). SHAP revealed co
Cardiovascular diseases are major causes of mortality globally. They often co-occur and are interrelated, leading to partial-order relationships among their onset times. However, these onset times are subject to informative censoring due to the occurrence of death, posing significant challenges for survival prediction. In this article, we propose a novel copula-based framework that learns dependence among multiple correlated marginal components through a pseudo-likelihood for estimation. We adopt nonparametric marginals, alleviating the reliance on marginal distribution assumptions typically required in conventional copula models, and estimate the association between the onsets of intermediate cardiovascular diseases and death by solving a concordance estimating equation. Under this framework, a renewable risk assessment method is developed for dynamic survival prediction, leveraging information on disease onset times and the maximum follow-up duration. Our proposed method yields estimators with well-established properties, and its flexibility and predictive effectiveness are demonstrated through extensive simulation studies. We apply the method to data from a heart disease study,
BACKGROUND: There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. METHODS: We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. RESULTS: The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P<0.001), and yielded a net reclassification improvement of 1.52% and 0.83%, respectively, for the predicted 10-year risk categories of "low" (<10%), "intermediate" (10% to <20%), and "high" (≥20%) (P<0.02 for both comparisons). We estimated that among 100,000 adults 40 years of age or older, 15,025 persons would initially be classified as being at intermediate risk for a cardiovascular event if conventional risk factors alone were used to calculate risk. Assuming that statin therapy would be initiated in accordance with Adult Treatment Panel III guidelines (i.e., for persons with a predicted risk of ≥20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. CONCLUSIONS: In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.).
BACKGROUND: In patients with coronary heart disease and a broad range of cholesterol levels, cholesterol-lowering therapy reduces the risk of coronary events, but the effects on mortality from coronary heart disease and overall mortality have remained uncertain. METHODS: In a double-blind, randomized trial, we compared the effects of pravastatin (40 mg daily) with those of a placebo over a mean follow-up period of 6.1 years in 9014 patients who were 31 to 75 years of age. The patients had a history of myocardial infarction or hospitalization for unstable angina and initial plasma total cholesterol levels of 155 to 271 mg per deciliter. Both groups received advice on following a cholesterol-lowering diet. The primary study outcome was mortality from coronary heart disease. RESULTS: Death from coronary heart disease occurred in 8.3 percent of the patients in the placebo group and 6.4 percent of those in the pravastatin group, a relative reduction in risk of 24 percent (95 percent confidence interval, 12 to 35 percent; P<0.001). Overall mortality was 14.1 percent in the placebo group and 11.0 percent in the pravastatin group (relative reduction in risk, 22 percent; 95 percent confidence interval, 13 to 31 percent; P<0.001). The incidence of all cardiovascular outcomes was consistently lower among patients assigned to receive pravastatin; these outcomes included myocardial infarction (reduction in risk, 29 percent; P<0.001), death from coronary heart disease or nonfatal myocardial infarction (a 24 percent reduction in risk, P<0.001), stroke (a 19 percent reduction in risk, P=0.048), and coronary revascularization (a 20 percent reduction in risk, P<0.001). The effects of treatment were similar for all predefined subgroups. There were no clinically significant adverse effects of treatment with pravastatin. CONCLUSIONS: Pravastatin therapy reduced mortality from coronary heart disease and overall mortality, as compared with the rates in the placebo group, as well as the incidence of all prespecified cardiovascular events in patients with a history of myocardial infarction or unstable angina who had a broad range of initial cholesterol levels.
Cardiovascular diseases (CVD) are the leading cause of death globally. Non-invasive, cost-effective imaging techniques play a crucial role in early detection and prevention of CVD. Optical coherence tomography (OCT) has gained recognition as a potential tool for early CVD risk prediction, though its use remains underexplored. In this study, we investigated the potential of OCT as an additional imaging technique to predict future CVD events. We analysed retinal OCT data from the UK Biobank. The dataset included 612 patients who suffered a myocardial infarction (MI) or stroke within five years of imaging and 2,234 controls without CVD (total: 2,846 participants). A self-supervised deep learning approach based on Variational Autoencoders (VAE) was used to extract low-dimensional latent representations from high-dimensional 3D OCT images, capturing distinct features of retinal layers. These latent features, along with clinical data, were used to train a Random Forest (RF) classifier to differentiate between patients at risk of future CVD events (MI or stroke) and healthy controls. Our model achieved an AUC of 0.75, sensitivity of 0.70, specificity of 0.70, and accuracy of 0.70, outperf
Heart disease is the major cause of non-communicable and silent death worldwide. Heart diseases or cardiovascular diseases are classified into four types: coronary heart disease, heart failure, congenital heart disease, and cardiomyopathy. It is vital to diagnose heart disease early and accurately in order to avoid further injury and save patients' lives. As a result, we need a system that can predict cardiovascular disease before it becomes a critical situation. Machine learning has piqued the interest of researchers in the field of medical sciences. For heart disease prediction, researchers implement a variety of machine learning methods and approaches. In this work, to the best of our knowledge, we have used the dataset from IEEE Data Port which is one of the online available largest datasets for cardiovascular diseases individuals. The dataset isa combination of Hungarian, Cleveland, Long Beach VA, Switzerland & Statlog datasets with important features such as Maximum Heart Rate Achieved, Serum Cholesterol, Chest Pain Type, Fasting blood sugar, and so on. To assess the efficacy and strength of the developed model, several performance measures are used, such as ROC, AUC curv
Rankings of scholarly journals based on citation data are often met with skepticism by the scientific community. Part of the skepticism is due to disparity between the common perception of journals' prestige and their ranking based on citation counts. A more serious concern is the inappropriate use of journal rankings to evaluate the scientific influence of authors. This paper focuses on analysis of the table of cross-citations among a selection of Statistics journals. Data are collected from the Web of Science database published by Thomson Reuters. Our results suggest that modelling the exchange of citations between journals is useful to highlight the most prestigious journals, but also that journal citation data are characterized by considerable heterogeneity, which needs to be properly summarized. Inferential conclusions require care in order to avoid potential over-interpretation of insignificant differences between journal ratings. Comparison with published ratings of institutions from the UK's Research Assessment Exercise shows strong correlation at aggregate level between assessed research quality and journal citation `export scores' within the discipline of Statistics.
Cardiovascular diseases are the leading cause of mortality globally, necessitating advancements in diagnostic techniques. This study explores the application of wavelet transformation for classifying electrocardiogram (ECG) signals to identify various cardiovascular conditions. Utilizing the MIT-BIH Arrhythmia Database, we employed both continuous and discrete wavelet transforms to decompose ECG signals into frequency sub-bands, from which we extracted eight statistical features per band. These features were then used to train and test various classifiers, including K-Nearest Neighbors and Support Vector Machines, among others. The classifiers demonstrated high efficacy, with some achieving an accuracy of up to 96% on test data, suggesting that wavelet-based feature extraction significantly enhances the prediction of cardiovascular abnormalities in ECG data. The findings advocate for further exploration of wavelet transforms in medical diagnostics to improve automation and accuracy in disease detection. Future work will focus on optimizing feature selection and classifier parameters to refine predictive performance further.
Guidelines aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of guidelines have been issued in recent years by different organizations-European Society of Cardiology (ESC), American Heart Association (AHA), American College of Cardiology (ACC), and other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing guidelines. In spite of the fact that standards for issuing good quality guidelines are well defined, recent surveys of guidelines published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilization of health resources. In addition, the legal implications of medical guidelines have been discussed and examined, resulting in position documents, which have been published by a specific Task Force. The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these guidelines or statements. The rationale for an active approach to the prevention of cardiovascular diseases (CVD) is …
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.
BACKGROUND: Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide. METHODS: We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of ≥50 years with established cardiovascular or chronic kidney disease, or age of ≥60 years with cardiovascular risk factors only). The primary outcome in a time-to-event analysis was the first occurrence of a major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The trial was designed to rule out 80% excess cardiovascular risk as compared with placebo (noninferiority margin of 1.8 for the upper boundary of the 95% confidence interval for the hazard ratio for the primary outcome). RESULTS: A total of 3183 patients were randomly assigned to receive oral semaglutide or placebo. The mean age of the patients was 66 years; 2695 patients (84.7%) were 50 years of age or older and had cardiovascular or chronic kidney disease. The median time in the trial was 15.9 months. Major adverse cardiovascular events occurred in 61 of 1591 patients (3.8%) in the oral semaglutide group and 76 of 1592 (4.8%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.57 to 1.11; P<0.001 for noninferiority). Results for components of the primary outcome were as follows: death from cardiovascular causes, 15 of 1591 patients (0.9%) in the oral semaglutide group and 30 of 1592 (1.9%) in the placebo group (hazard ratio, 0.49; 95% CI, 0.27 to 0.92); nonfatal myocardial infarction, 37 of 1591 patients (2.3%) and 31 of 1592 (1.9%), respectively (hazard ratio, 1.18; 95% CI, 0.73 to 1.90); and nonfatal stroke, 12 of 1591 patients (0.8%) and 16 of 1592 (1.0%), respectively (hazard ratio, 0.74; 95% CI, 0.35 to 1.57). Death from any cause occurred in 23 of 1591 patients (1.4%) in the oral semaglutide group and 45 of 1592 (2.8%) in the placebo group (hazard ratio, 0.51; 95% CI, 0.31 to 0.84). Gastrointestinal adverse events leading to discontinuation of oral semaglutide or placebo were more common with oral semaglutide. CONCLUSIONS: In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo. (Funded by Novo Nordisk; PIONEER 6 ClinicalTrials.gov number, NCT02692716.).
BACKGROUND: Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of CVD is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with CVD. The case for primary prevention was uncertain when the last version of this review was published (2011) and in light of new data an update of this review is required. OBJECTIVES: To assess the effects, both harms and benefits, of statins in people with no history of CVD. SEARCH METHODS: To avoid duplication of effort, we checked reference lists of previous systematic reviews. The searches conducted in 2007 were updated in January 2012. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2022, Issue 4), MEDLINE OVID (1950 to December Week 4 2011) and EMBASE OVID (1980 to 2012 Week 1).There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of statins versus placebo or usual care control with minimum treatment duration of one year and follow-up of six months, in adults with no restrictions on total, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted data. Outcomes included all-cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), revascularisation, change in total and LDL cholesterol concentrations, adverse events, quality of life and costs. Odds ratios (OR) and risk ratios (RR) were calculated for dichotomous data, and for continuous data, pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated. We contacted trial authors to obtain missing data. MAIN RESULTS: The latest search found four new trials and updated follow-up data on three trials included in the original review. Eighteen randomised control trials (19 trial arms; 56,934 participants) were included. Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event. AUTHORS' CONCLUSIONS: Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.
CONTEXT: Patients with renal disease are at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority. OBJECTIVE: To quantify the representation of patients with renal disease in randomized controlled trials for interventions proven efficacious for cardiovascular disease. DATA SOURCES: We searched MEDLINE for trials published from 1985 through 2005 in 11 major medical and subspecialty journals. STUDY SELECTION: Randomized controlled trials for chronic congestive heart failure and acute myocardial infarction of treatments that are currently listed as class I or II recommendations in the current American College of Cardiology/American Heart Association guidelines were included. DATA EXTRACTION: Two reviewers independently abstracted data on study and patient characteristics, renal measurements, outcomes, and prognostic features. DATA SYNTHESIS: A total of 153 trials were reviewed. Patients with renal disease were reported as excluded in 86 (56%) trials. Patients with renal disease were more likely to be excluded from trials that were multicenter; of moderate enrollment size; North American; that tested renin-angiotensin-aldosterone system antagonists and anticoagulants; and that tested chronic congestive heart failure. Only 8 (5%) original articles reported the proportion of enrolled patients with renal disease, and only 15 (10%) reported mean baseline renal function. While 81 (53%) trials performed subgroup analyses of some baseline characteristic in the original article, only 4 (3%) subgroup analyses of treatment stratified by renal disease were performed. CONCLUSION: Major cardiovascular disease trials frequently exclude patients with renal disease and do not provide adequate information on the renal function of enrollees or the effect of interventions on patients with renal disease.