A Causal Model for Primary Prevention of Cardiovascular Disease: The Health Economic Model for the Primary Prevention of Cardiovascular Disease.

OBJECTIVES: Our objective was to design and develop an open-source model capable of simulating interventions for primary prevention of cardiovascular disease (CVD) that incorporated the cumulative effects of risk factors (eg, cholesterol years or blood-pressure years) to enhance health economic modeling in settings which clinical trials are not possible. METHODS: We reviewed the literature to design the model structure by selecting the most important causal risk factors for CVD-low-density lipoprotein-cholesterol (LDL-C), systolic blood pressure (SBP), smoking, diabetes, and lipoprotein (a) (Lp(a))-and most common CVDs-myocardial infarction and stroke. The epidemiological basis of the model involves the simulation of risk factor trajectories, which are used to modify CVD risk via causal effect estimates derived from Mendelian randomization. LDL-C, SBP, Lp(a), and smoking all have cumulative impacts on CVD risk, which were incorporated into the health economic model. The data for the model were primarily sourced from the UK Biobank study. We calibrated the model using clinical trial data and validated the model against the observed UK Biobank data. Finally, we performed an example health economic analysis to demonstrate the utility of the model. The model is open source. RESULTS: The model performed well in all validation tests. It was able to produce interpretable and plausible (consistent with expectations of the existing literature) results from an example health economic analysis. CONCLUSIONS: We have constructed an open-source health economic model capable of incorporating the cumulative effect of LDL-C (ie, cholesterol years), SBP (SBP-years), Lp(a), and smoking on lifetime CVD risk.

The cost-effectiveness of semaglutide in reducing cardiovascular risk among people with overweight and obesity and existing cardiovascular disease, but without diabetes.

BACKGROUND AND AIMS: The Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial demonstrated significant reductions in cardiovascular outcomes in people with cardiovascular disease (CVD) and overweight or obesity (but without diabetes). However, the cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. This study explored whether use of semaglutide for the secondary prevention of CVD in overweight or obesity is cost-effective from the Australian healthcare perspective. METHODS: A Markov model was developed based on the SELECT trial to model the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo, in addition to standard care, and followed up over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events or dying. Model inputs were derived from SELECT and published literature. Costs were obtained from Australian sources. All outcomes were discounted by 5% annually. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. RESULTS: With an annual estimated cost of semaglutide of A${\$}$4175, the model resulted in ICERs of A${\$}$99 853 (US${\$}$143 504; £40 873) per YoLS and A${\$}$96 055 (US${\$}$138 046; £39 318) per QALY gained. CONCLUSIONS: Assuming a willingness-to-pay threshold of A${\$}$50 000, semaglutide is not considered cost-effective at the current price. A price of ≤ A${\$}$2000 per year or more targeted use in high-risk patients would be needed for it to be considered cost-effective in the Australian setting.

Association of Drug-Disease Interactions with Mortality or Readmission in Hospitalised Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Multimorbidity is common in hospitalised adults who are at increased risk of inappropriate prescribing including drug-disease interactions. These interactions occur when a medicine being used to treat one condition exacerbates a concurrent medical condition and may lead to adverse health outcomes. The aim of this review was to examine the association between drug-disease interactions and the risk of mortality and readmission in hospitalised middle-aged and older adults. METHODS: A systematic review was conducted on drug-disease interactions in hospitalised middle-aged (45-64 years) and older adults (≥65 years). The study protocol was prospectively registered with PROSPERO (Registration Number: CRD42022341998). Drug-disease interactions were defined as a medicine being used to treat one condition with the potential to exacerbate a concurrent medical condition or that were inappropriate based on a comorbid medical condition. Both observational and interventional studies were included. The outcomes of interest were mortality and readmissions. The databases searched included MEDLINE, CINAHL, EMBASE, Web of Science, SCOPUS and the Cochrane Library from inception to 12 July, 2022. A meta-analysis was performed to pool risk estimates using the random-effects model. RESULTS: A total of 563 studies were identified and four met the inclusion criteria. All were observational studies in older adults, with no studies identified in middle-aged adults. Most of the studies were at risk of bias because of an inadequate adjustment for covariates and a lack of clarity around individuals lost to follow-up. There were various definitions of drug-disease interactions within these four studies. Two studies assessed drugs that were contraindicated based on renal function, one assessed an individual drug-disease combination, and one was based on the clinical judgement of a pharmacist. There were two studies that showed an association between drug-disease interactions and the outcomes of interest. One reported that the use of diltiazem in patients with heart failure was associated with an increased risk of readmissions. The second reported that the use of medicines contraindicated according to renal function were associated with increased risk of all-cause mortality and a composite of mortality and readmission. Three of the studies (total study population = 5705) were amenable to a meta-analysis, which showed no significant association between drug-disease interactions and readmissions (odds ratio = 1.0, 95% confidence interval 0.80-1.38). CONCLUSIONS: Few studies were identified examining the risk of drug-disease interactions and mortality and readmission in hospitalised adults. Most of the identified studies were at risk of bias. There is no universal accepted definition of drug-disease interactions in the literature. Further studies are needed to develop a standardised and accepted definition of these interactions to guide further research in this area.

Prevalence and Predictors of Emergency Medical Service Use in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

AIM: We aim to describe prevalence of Emergency Medical Service (EMS) use, investigate factors predictive of EMS use, and determine if EMS use predicts treatment delay and mortality in our ST-elevation myocardial infarction (STEMI) cohort. METHOD: We prospectively collected data on 5,602 patients presenting with STEMI for primary percutaneous coronary intervention (PCI) transported to PCI-capable hospitals in Victoria, Australia, from 2013-2018 who were entered into the Victorian Cardiac Outcomes Registry (VCOR). We linked this dataset to the Ambulance Victoria and National Death Index (NDI) datasets. We excluded late presentation, thrombolysed, and in-hospital STEMI, as well as patients presenting with cardiogenic shock and out-of-hospital cardiac arrest. RESULTS: In total, 74% of patients undergoing primary PCI for STEMI used EMS. Older age, female gender, higher socioeconomic status, and a history of prior ischaemic heart disease were independent predictors of using EMS. EMS use was associated with shorter adjusted door-to-balloon (53 vs 72 minutes, p<0.001) and symptom-to-balloon (183 vs 212 minutes, p<0.001) times. Mode of transport was not predictive of 30-day or 12-month mortality. CONCLUSIONS: EMS use in Victoria is relatively high compared with internationally reported data. EMS use reduces treatment delay. Predictors of EMS use in our cohort are consistent with those prevalent in prior literature. Understanding the patients who are less likely to use EMS might inform more targeted education campaigns in the future.

SGLT2 Inhibitor-Associated Ketoacidosis vs Type 1 Diabetes-Associated Ketoacidosis.

This cohort study examines the natural history and response to treatment of sodium glucose cotransporter 2 (SGLT2) inhibitor­associated ketoacidosis compared with that of type 1 diabetes­associated ketoacidosis.

Infectious and sepsis presentations to, and hospital admissions from emergency departments in Victoria, Australia.

OBJECTIVE: To investigate the frequency and outcomes of adult infectious and sepsis presentations to, and hospital admissions from, Emergency Departments (EDs) in Victoria, Australia. METHODS: Retrospective cohort study using the Victorian Emergency Minimum Dataset and Victorian Admitted Episodes Dataset. We included adults (age ≥ 18 years) presenting to an ED, or admitted to hospital from ED in Victoria between July 2017 and June 2018. One-year mortality was analysed until June 2019 using the Victorian Death Index, and ICD-10 coding was used to identify cases. RESULTS: Among 1.28 million ED presentations over 1 year, 12.00% and 0.45% were coded with infectious and sepsis diagnoses, respectively. Despite having lower triage categories, patients with infections were more likely to be admitted to hospital (50.4% vs 44.9%), but not directly to ICU (0.8%). Patients coded with sepsis were assigned higher triage categories and required hospital admission much more frequently (96.4% vs 44.9%), including to ICU (15.9% vs 0.8%). Patients presenting with infections and sepsis had increased risk of 1-year mortality (adjusted hazard ratio 1.44 and 4.13, respectively). Of the 648 280 hospital admissions from the ED, infection and sepsis were coded in 23.69% and 2.66%, respectively, and the adjusted odds ratio for 1-year mortality were 1.64 and 4.79, respectively. CONCLUSIONS: Infections and sepsis are common causes of presentation to, and admission from the ED in Victoria. Such patients experience higher mortality than non-infectious patients, even after adjusting for age. There is a need to identify modifiable factors contributing to these outcomes.

Digital Health for Myocardial Infarction: Research Topics and Trends.

We aimed to map the topics and trends of research on digital health for myocardial infarction over the past ten years. This can inform future research directions and newly emerging topics for myocardial infarction care, diagnosis and monitoring. The Web of Science database was searched for papers related to digital health for myocardial infarction. 1,344 retrieved records were used for visualisation through bibliometrics and co-occurrence network analysis of keywords. Our mapping revealed several emerging topics in recent years, including artificial intelligence and deep learning. Higher emphasis on automated and artificially intelligent digital health systems in recent years can inform future clinical practice and research directions for myocardial infarction.

Societal health and economic burden of cardiovascular diseases in the population with type 2 diabetes in Qatar. A 10-year forecasting model.

AIMS: To predict the future health and economic burden of cardiovascular disease (CVD) in type 2 diabetes (T2D) in Qatar. MATERIALS AND METHODS: A dynamic multistate model was designed to simulate the progression of fatal and non-fatal CVD events among people with T2D in Qatar aged 40-79 years. First CVD events [i.e. myocardial infarction (MI) and stroke] were calculated via the 2013 Pooled Cohort Equation, while recurrent CVD events were sourced from the REACH registry. Key model outcomes were fatal and non-fatal MI and stroke, years of life lived, quality-adjusted life years, total direct medical costs and total productivity loss costs. Utility and cost model inputs were drawn from published sources. The model adopted a Qatari societal perspective. Sensitivity analyses were performed to test the robustness of estimates. RESULTS: Over 10 years among people with T2D, model estimates 108 195 [95% uncertainty interval (UI) 104 249-112 172] non-fatal MIs, 62 366 (95% UI 60 283-65 520) non-fatal strokes and 14 612 (95% UI 14 472-14 744) CVD deaths. The T2D population accrued 4 786 605 (95% UI 4 743 454, 4 858 705) total years of life lived and 3 781 833 (95% UI 3 724 718-3 830 669) total quality-adjusted life years. Direct costs accounted for 57.85% of the total costs, with a projection of QAR41.60 billion (US$11.40 billion) [95% UI 7.53-147.40 billion (US$2.06-40.38 billion)], while the total indirect costs were expected to exceed QAR30.31 billion (US$8.30 billion) [95% UI 1.07-162.60 billion (US$292.05 million-44.55 billion)]. CONCLUSIONS: The findings suggest a significant economic and health burden of CVD among people with T2D in Qatar and highlight the need for more enhanced preventive strategies targeting this population group.