Cardiovascular events among patients with prostate cancer treated with abiraterone and enzalutamide.

BACKGROUND AND PURPOSE: There is growing concern about the adverse metabolic and cardiovascular effects of abiraterone acetate (AA) and enzalutamide (ENZ), two standard hormonal therapies for prostate cancer. We analysed the risk of cardiovascular adverse events among patients treated with AA and ENZ. PATIENTS AND METHODS: We used Kythera Medicare data from January 2019 to June 2023 to identify patients with at least one pharmacy claim for AA or ENZ. The index date was the first prescription claim date. Patients were required to have 1 year of data pre- and post-index date. New users excluded those with prior AA or ENZ claims and pre-existing cardiovascular comorbidities. Demographic and clinical variables, including age, socioeconomic status (SES), comorbidity score, prostate-specific comorbidities, and healthcare costs, were analysed . Propensity score matching was employed for risk adjustment. RESULTS: Of the 8,929 and 8,624 patients in the AA and ENZ cohorts, respectively, 7,647 were matched after adjusting for age, sociodemographic, and clinical factors. Between the matched cohorts (15.54% vs. 14.83%, p < 0.05), there were no statistically significant differences in any cardiovascular event after adjusting for these factors. The most common cardiovascular event in both cohorts was heart failure (5.20% vs. 4.49%), followed by atrial fibrillation (4.42% vs. 3.60%) and hypotension (2.93% vs. 2.48%). INTERPRETATION: This study provides real-world evidence of the cardiovascular risk of AA and ENZ that may not appear in clinical trial settings. Adjusting for age, baseline comorbidities, and SES, the likelihood of a cardiovascular event did not differ between treatment groups.

Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

Early-life exposure to ambient air pollution with cardiovascular risk factors in adolescents: Findings from the "Children of 1997" Hong Kong birth cohort.

BACKGROUND: Long-term exposure to ambient air pollution is associated with cardiovascular disease (CVD) risk. Little is known about the impact of early-life exposure to air pollutants on CVD risk factors in late adolescence, which may track into adulthood. To clarify, we examined this question in a unique setting with high air pollution and a high level of economic development. METHODS: This study leveraged the "Children of 1997" Hong Kong birth cohort (N = 8327), including here 3350 participants. We estimated ambient air pollutant exposure including inhalable particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and nitrogen monoxide (NO) by growth phase (in utero, infancy, childhood) and overall based on residential address. Generalized linear regression was used to assess the associations of air pollutants exposure by growth phase and sex with CVD risk factors (fasting blood glucose, glycosylated hemoglobin, lipid profile, blood pressure, and body mass index) at 17.6 years. We also assessed whether associations varied by sex. RESULTS: Early life exposed had little association with glucose metabolism, blood pressure or body mass index, but after considering multiple comparisons early exposure to PM10 was associated with low density lipoprotein (LDL) in boys, with ß and 95 % confidence intervals (95 % CI) of 0.184 (0.069 to 0.298) mmol/l, 0.151 (0.056 to 0.248) mmol/l, and 0.157 (0.063 to 0.252) mmol/l by per interquartile range (IQR) increment of PM10 for in utero, infancy, and overall, respectively. No such associations were evident for girls, differences by sex were evident. CONCLUSIONS: Our study suggested sex-specific associations of early-life PM10 exposure with elevated LDL in adolescence, especially exposure in utero and infancy.

Short term exposure to low level ambient fine particulate matter and natural cause, cardiovascular, and respiratory morbidity among US adults with health insurance: case time series study.

OBJECTIVE: To estimate the excess relative and absolute risks of hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease associated with daily exposure to fine particulate matter (PM2.5) at concentrations below the new World Health Organization air quality guideline limit among adults with health insurance in the contiguous US. DESIGN: Case time series study. SETTING: US national administrative healthcare claims database. PARTICIPANTS: 50.1 million commercial and Medicare Advantage beneficiaries aged ≥18 years between 1 January 2010 and 31 December 2016. MAIN OUTCOME MEASURES: Daily counts of hospital admissions and emergency department visits for natural causes, cardiovascular disease, and respiratory disease based on the primary diagnosis code. RESULTS: During the study period, 10.3 million hospital admissions and 24.1 million emergency department visits occurred for natural causes among 50.1 million adult enrollees across 2939 US counties. The daily PM2.5 levels were below the new WHO guideline limit of 15 µg/m3 for 92.6% of county days (7 360 725 out of 7 949 713). On days when daily PM2.5 levels were below the new WHO air quality guideline limit of 15 µg/m3, an increase of 10 µg/m3 in PM2.5 during the current and previous day was associated with higher risk of hospital admissions for natural causes, with an excess relative risk of 0.91% (95% confidence interval 0.55% to 1.26%), or 1.87 (95% confidence interval 1.14 to 2.59) excess hospital admissions per million enrollees per day. The increased risk of hospital admissions for natural causes was observed exclusively among adults aged ≥65 years and was not evident in younger adults. PM2.5 levels were also statistically significantly associated with relative risk of hospital admissions for cardiovascular and respiratory diseases. For emergency department visits, a 10 µg/m3 increase in PM2.5 during the current and previous day was associated with respiratory disease, with an excess relative risk of 1.34% (0.73% to 1.94%), or 0.93 (0.52 to 1.35) excess emergency department visits per million enrollees per day. This association was not found for natural causes or cardiovascular disease. The higher risk of emergency department visits for respiratory disease was strongest among middle aged and young adults. CONCLUSIONS: Among US adults with health insurance, exposure to ambient PM2.5 at concentrations below the new WHO air quality guideline limit is statistically significantly associated with higher rates of hospital admissions for natural causes, cardiovascular disease, and respiratory disease, and with emergency department visits for respiratory diseases. These findings constitute an important contribution to the debate about the revision of air quality limits, guidelines, and standards.

Cardiovascular diseases burden attributable to ambient PM2.5 pollution from 1990 to 2019: A systematic analysis for the global burden of disease study 2019.

BACKGROUND: Ambient PM2.5 pollution (APMP2.5) was the leading environmental risk factor for cardiovascular diseases (CVDs) worldwide. An up-to-date comprehensive study is needed to provide global epidemiological patterns. METHODS: Detailed data on CVDs burden attributable to APMP2.5 were obtained from the Global Burden of Disease Study (GBD) 2019. We calculated the estimated annual percentage change (EAPC) to assess temporal trends in age-standardized rates of deaths and disability-adjusted life years (DALYs) over 30 years. RESULTS: Globally, CVDs attributable to APMP2.5 resulted in 2.48 million deaths and 60.91 million DALYs, with an increase of 122%, respectively from 1990 to 2019. In general, men suffered markedly higher burden than women, but the gap will likely turn narrow. As for age distribution, CVDs deaths and DALYs attributable to APMP2.5 mainly occurred in the elder group (>70 years). Low- and middle-income regions endured the higher CVDs burden due to the higher exposure to APMP2.5, and the gap may potentially expand further compared with high-income regions. For regions, the highest age-standardized rates of APMP2.5-related CVDs deaths and DALYs were observed mainly in Central Asia, while the lowest was observed in Australasia. At the national level, countries with the largest ASDR decline were clustered in western Europe, while Equatorial Guinea, Timor-Leste and Bhutan exhibited relatively rapid increases over this period. CONCLUSIONS: The global CVDs burden attributable to APMP2.5 has contributed to the heterogeneity of spatial and temporal distribution. APMP2.5-related CVDs deaths have largely shifted from higher SDI regions to those with a lower SDI. Globally, APMP2.5-attributable CVDs pose a significant threat to public health and diseases burden has increased over time, particularly in male, old-aged populations. The governments and health systems should take measures to reduce air pollution to impede this rising trend.

Assessment of vitamin B12 levels and cardiovascular risk factors in metformin- and non-metformin-treated type 2 diabetic patients.

Oxidative stress enhances cardiovascular risk. Metformin decreases intestinal absorption of vitamin B12. Our objective was the evaluation of type 2 diabetics focusing on differences due to their treatment. A prospective study on 224 type 2 diabetics was realized between 2015-2018 in Targu Mures, Romania, divided into 2 subgroups (metformin vs. other therapy - 2nd/3rd generation sulfonylureas, insulin, dietary regimen -, followed for at least one year) and non-diabetic controls (n=25) for oxidative stress level comparison. Serum homocysteine (HC), vitamin B12 were determined by chemiluminescence (Immulite One). Lipid peroxidation was assessed by serum malondialdehyde (MDA) measurement (HPLC). Biochemical tests, minerals, cystatin C, high-sensitivity C reactive protein (hs-CRP) were measured on Konelab20Xti, glycated hemoglobin on Nycocard Reader. GraphPad InStat-3 was used for statistics. Negative correlation occured between serum vitamin B12 and HC, this vitamin's level was significantly lower and serum zinc was significantly higher in patients on metformin. Hyperhomocysteinemia was present in 87% of the subjects, 46% had zinc deficiency and 41% elevated hs-CRP. Serum cystatin C showed positive correlation with creatinine. Serum MDA was significantly higher in diabetics compared to control patients. Elevated hs-CRP and homocysteine represent raised cardiovascular risk. Intense oxidative stress, vitamin, mineral deficiencies are frequent in diabetic subjects.

Major cardiovascular events increase in long-term proprotein convertase subtilisin/kexin type 9 inhibitors therapy: the Tuscany cost-effective study.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a breakthrough in the treatment of hypercholesterolemia. The aim of this study was to perform a multicentre prospective analysis on the effects of PCSK9i since their distribution in Italy. METHODS: During the study period (July 2017 to February 2022) 246 patients (mean age 61 ±â€Š11 years, male 73%) who were evolocumab (142/246) or alirocumab (104/246) new users were enrolled in the CERTI (Costo Efficacia Regione Toscana Inibitori PCSK9) study. Lipid value, adverse events (AEs), major cardiovascular events (MACEs) and intima-media thickness were analysed. RESULTS: PCSK9i therapy allowed a significant improvement in patients' lipid profile [total cholesterol -35%, P < 0.001; triglycerides -9%, P < 0.05; low-density lipoprotein (LDL) cholesterol -51%, P < 0.001; Lp(a) levels -4%, P < 0.05], maintained during the follow-up. No significant variations in intima-media thickness were observed. In the subgroup of patients with more than 1 year of PCSK9i therapy (165/246 patients) we highlighted: a 66% reduction in MACEs compared with the year before recruitment; a progressive increase in MACEs during the follow-up (MACEs event/rate at first year 0.08 vs. MACEs event/rate at year 5: 0.47); a patients cluster with late MACEs older, with higher prevalence of hypertension, smoking habit and peripheral vascular disease. During the follow-up, we recorded AEs in 31% of patients, which mainly resulted in reduction/discontinuation of lipid-lowering therapy for 50 patients or in discontinuation/shift of PCSK9i (respectively 8 and 6 cases). CONCLUSION: Our data agree with the large evidence on the effectiveness/tolerability of PCSK9i therapy; however, although PCSK9i represents a good cholesterol-lowering therapeutic option, our study shows a progressive increase in MACEs during the late follow-up that deserve further research.

Trends in Upper Gastrointestinal Bleeding in Patients on Primary Prevention Aspirin: A Nationwide Emergency Department Sample Analysis, 2016-2020.

BACKGROUND: Recent guidelines do not recommend routine use of aspirin for primary cardiovascular prevention (ppASA) and suggest avoidance of ppASA in older individuals due to bleeding risk. However, ppASA is frequently taken without an appropriate indication. Estimates of the incidence of upper gastrointestinal bleeding due to ppASA in the United States are lacking. In this study, we provide national estimates of upper gastrointestinal bleeding incidence, characteristics, and costs in ppASA users from 2016-2020. METHODS: Primary cardiovascular prevention users (patients on long-term aspirin therapy without cardiovascular disease) presenting with upper gastrointestinal bleeding were identified in the Nationwide Emergency Department Sample using International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. Trends in upper gastrointestinal bleeding incidence, etiology, severity, associated Medicare reimbursements, and the impact of ppASA on bleeding outcomes were assessed with regression models. RESULTS: From 2016-2020, adjusted incidence of upper gastrointestinal bleeding increased 29.2% among ppASA users, with larger increases for older patients (increase of 41.6% for age 65-74 years and 36.0% for age ≥75 years). The most common etiology among ppASA users was ulcer disease but increases in bleeding incidence due to angiodysplasias were observed. The proportion of hospitalizations with major complications or comorbidities increased 41.5%, and Medicare reimbursements increased 67.6%. Among patients without cardiovascular disease, ppASA was associated with increased odds of hospital admission, red blood cell transfusion, and endoscopic intervention as compared to no ppASA use. CONCLUSIONS: Considering recent guideline recommendations, the rising incidence, severity, and costs associated with upper gastrointestinal bleeding among patients on ppASA highlights the importance of careful assessment for appropriate ppASA use.

Cardiovascular Risk Assessment After Sofosbuvir And Daclatasvir Regimen For Chronic Hepatitis C Virus Infection.

Objectives: To assess cardiovascular risk after sofosbuvir and daclatasvir antiviral combination therapy in chronic hepatitis C virus patients. Method: The prospective cohortstudy was conducted at the Kafrelsheikh University Hospital, Egypt, from December 2019 to December 2021, and comprised adult patients of either gender with chronic hepatitis C virus and with minimum ejection fraction 40%. They were classified into groups according to their cardiovascular risk. Group 1 had individuals with no risk factors, Group 2 had patients with many risk factors, Group 3 had patients with only hypertension, Group 4 had those with diabetes alone, and Group 5 comprised smokers. All the patients were evaluated for the risk of major cardiovascular events at baseline and at the end of 12-week of antiviral combination therapy of sofosbuvir 400 mg once daily dose and daclatasvir 60 mg once daily dose. Data was analysed with SPSS version 23. RESULTS: Of the 200 patients, there were 96(48%) males and 104(52%) females. The age ranged 34-81 years. There were 78(39%) patients in Group 1; 20(25.6%) males and 58(74.4%) females with mean age 54.4±10.45 years. Group 2 had 60(30%) patients; 40(66.6%) males and 20(33.3%) females with mean age 59.57±9.1 years. Group 3 had 25(12.5%) patients; 3(12%) males and 22(88%) females with mean age 61.4±7.8 years. Group 4 had 13(6.5%) patients; 10(77%) males and 3(23%) females with mean age 55.4±10.4 years. Group 5 had 24(12%) patients who were all (100%) males with mean age 60.7±5.7 years. There were non-significant changes in the incidence of angina, arrhythmias or progression of dyspnoea (p>0.05). Echocardiography follow-up results showed non-significant changes in mean ejection fraction, global longitudinal strain and pulmonary artery pressure (p>0.05). CONCLUSIONS: Sofosbuvir and daclatasvir combination therapy wasfound to be safe in chronic hepatitis C virus patients regarding cardiac risks.

Cardiovascular health among persons with HIV without existing atherosclerotic cardiovascular disease.

OBJECTIVES: We sought to characterize atherosclerotic cardiovascular disease (ASCVD) risk and metrics of cardiovascular health in persons with HIV (PWH) eligible for primary prevention of ASCVD. DESIGN: A cross-sectional study of PWH 40 years and older without documented ASCVD who received care at three HIV clinics in San Francisco from 2019 to 2022. METHODS: We used ICD-10 codes and electronic health record data to assess ASCVD risk and cardiovascular health, as defined by the American Heart Association's Life's Essential 8 (LE8) metrics for nicotine exposure, BMI, lipids, glucose, and blood pressure (BP). RESULTS: Among 2567 PWH eligible for primary prevention of ASCVD, the median age was 55 years, 14% were women, and 95% were on antiretroviral therapy. Seventy-seven percent had undergone complete assessment of ASCVD risk factors, and 50% of these patients had intermediate-high ASCVD risk (≥7.5%). Of those with hypertension, 39% were prescribed an antihypertensive. Among those eligible, 43% were prescribed a statin. The mean LE8 cardiovascular health score [0--100 (best health)] was 55.1 for nicotine exposure, 71.3 for BMI, 70.4 for lipids, 81.2 for blood glucose, 56.0 for BP, with an average score of 66.2 across the five metrics. Patients with Medicare insurance, black patients, and those with sleep apnea and chronic kidney disease had on average lower cardiovascular health scores; patients with undetectable viral loads had higher cardiovascular health scores. CONCLUSION: We highlight opportunities for improving primary prevention of ASCVD among PWH, especially in the areas of guideline-based therapy, nicotine exposure, and BP control.

Telehealth Intervention to Improve Uptake of Evidence-Based Medications among Patients with Type 2 Diabetes and Heart Failure or Cardiovascular Disease.

INTRODUCTION: Sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide 1 receptor (GLP-1) agonists are recommended for patients with type two diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) to reduce cardiovascular-related mortality. The objective of this study was to evaluate a telehealth targeted medication review (TMR) program to identify patients for uptake of these evidence-based medications. METHODS: This was an observational descriptive study of a TMR program for Medicare-enrolled, Medication Therapy Management-eligible patients in one insurance plan. Prescription claims and patient interviews identified individuals who would benefit from SGLT-2 inhibitors or GLP-1 agonists. Facsimiles were sent to providers of patients with educational information about the targeted medications. Descriptive statistics described characteristics and proportion of patients prescribed targeted medications after 120 days. Bivariate statistical tests evaluated associations between age, sex, number of medications, number of providers, and poverty level with adoption of targeted medications. RESULTS: A total of 1106 of 1127 had a facsimile sent to their provider after a conversation with the patient. Among patients with a provider facsimile, 69 (6%) patients filled a prescription for a targeted medication after 120 days. There was a significant difference in age between individuals who started a targeted medication (67 ± 10 years) compared with patients who did not (71 ± 10 years) (p = 0.001). CONCLUSIONS: A TMR efficiently identified patients with T2D and ASCVD or HF who would benefit from evidence-based medications. Although younger patients were more likely to receive these medications, the overall uptake of these medications within four months of the intervention was lower than expected.

Safety-Related Drug Label Changes Following Large Post-Marketing Cardiometabolic Trials: A Review of European Public Assessment Reports.

Selective safety data collection may simplify late-stage clinical trials and improve their feasibility. However, the impact on increasing overall drug safety knowledge is unknown. The aim of this study is to evaluate how much safety information is added to the drug label based on large trials after initial authorization. Changes made to the "undesirable effects" section of the drug label of cardiometabolic agents approved between 2000 and 2020 based on the results of large (> 1,000 patient) clinical trials submitted to the European Medicines Agency (EMA) were evaluated. The study focused on glucose lowering, antithrombotic, and lipid-modifying agents. The primary outcome was the number of changes in adverse drug reactions in the drug label. The EMA reviewed 55 large trials concerning 25 cardiometabolic agents after the initial marketing authorization, which included 402,444 patients. Ultimately, 38 trials (69%) resulted in a safety section update, whereas 17 trials (31%) did not. Changes in listed adverse drug reactions were made following 19 trials (35%) for 12 agents: 77 adverse drug reactions were added, 11 were deleted, and the frequencies of 43 were changed. Most changes in adverse drug reactions arose from trials with antithrombotic agents (88%) and trials performed in a new population (92%). Large trials for cardiometabolic agents reported after authorization add limited new safety information on adverse drug reactions, especially when performed in the population studied prior to approval. This suggests that selective safety data collection does not reduce learnings from late stage cardiometabolic trials in populations comprehensively studied before.

The challenges and pitfalls of incorporating evidence from cardiovascular outcomes trials in health economic modelling of type 2 diabetes.

The clinical evidence base for evaluating modern type 2 diabetes interventions has expanded greatly in recent years, with numerous efficacious treatment options available (including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors). The cardiovascular safety of these interventions has been assessed individually versus placebo in numerous cardiovascular outcomes trials (CVOTs), statistically powered to detect differences in a composite endpoint of major adverse cardiovascular events. There have been growing calls to incorporate these data in the long-term modelling of type 2 diabetes interventions because current diabetes models were developed prior to the conduct of the CVOTs and therefore rely on risk equations developed in the absence of these data. However, there are numerous challenges and pitfalls to avoid when using data from CVOTs. The primary concerns are around the heterogeneity of the trials, which have different study durations, inclusion criteria, rescue medication protocols and endpoint definitions; this results in significant uncertainty when comparing two or more interventions evaluated in separate CVOTs, as robust adjustment for these differences is difficult. Analyses using CVOT data inappropriately can dilute clear evidence from head-to-head clinical trials, and blur healthcare decision making. Calibration of existing models may represent an approach to incorporating CVOT data into diabetes modelling, but this can only offer a valid comparison of one intervention versus placebo based on a single CVOT. Ideally, model development should utilize patient-level data from CVOTs to prepare novel risk equations that can better model modern therapies for type 2 diabetes.

Association between ambient air pollution and daily hospital visits for cardiovascular diseases in Wuhan, China: a time-series analysis based on medical insurance data.

Although evidence showed the adverse effects of air pollution on cardiovascular disease (CVDs), few studies were based on medically insured populations. We applied a generalized additive Poisson model (GAM) to estimate the short-term effects of ambient air pollution on a group of medically insured population in Wuhan, China. We extracted daily air pollution data, meteorological data, and daily hospital visits for CVDs. We found that the ambient air pollutants sulfur dioxide (SO2), nitrogen dioxide (NO2), ground-level ozone (O3) particulate matter (PM) with an aerodynamic diameter ≤10 µm (PM10), and those ≤2.5 µm (PM2.5) all increased the risk of daily hospital visits for CVDs. We also found that the effect of air pollution on daily hospital visits for CVDs is greater in the cold season than in the warm season. Our findings can be used as evidence that supports the formulation of policies for air pollution and CVDs.

Racial disparities in treatment-related cardiovascular toxicities amongst women with breast cancer: a scoping review.

PURPOSE: Black women often experience poorer breast cancer-related outcomes and higher mortality than white women. A contributor to this disparity may relate to the disproportionate burden of cancer treatment-related cardiovascular (CV) toxicities. The objective of this review is to identify studies that report racial differences in CV toxicity risk. METHODS: Medline and Embase were searched for studies that assessed CV toxicities as the outcome(s) and included Black and White women with breast cancer. Studies were selected based on inclusion/exclusion criteria and through the use of multiple reviewers. RESULTS: The review included 13 studies following a review of 409 citations and 49 full-text articles. All studies were retrospective and 8/13 utilized data from the Surveillance, Epidemiology, and End Results-Medicare linked database. Trastuzumab was the most frequently studied treatment. The proportion of Black women in these studies ranged from 5.5 to 63%. A majority of studies reported a higher risk of CV toxicity amongst Black women when compared to white women (93%). Black women had up to a two times higher risk of CV toxicity (HR, 2.73 (CI, 1.24 to 6.01)) compared to white women. Only one study evaluated the role of socioeconomic factors in explaining racial differences in CV toxicity; however, the disparity remained even after adjusting for these factors. CONCLUSIONS: There is a critical need for more longitudinal studies that evaluate multilevel factors (e.g., psychosocial, biological) that may help to explain this disparity. IMPLICATIONS FOR CANCER SURVIVORS: Black cancer survivors may require additional surveillance and mitigation strategies to decrease disproportionate burden of CV toxicities.

Simulation study on LDL cholesterol target attainment, treatment costs, and ASCVD events with bempedoic acid in patients at high and very-high cardiovascular risk.

BACKGROUND AND AIMS: The LDL cholesterol (LDL-C) treatment goals recommended by the 2019 ESC/EAS guidelines are only achieved in a minority of patients. The study objective was to estimate the impact of bempedoic acid treatment on LDL-C target attainment, drug costs, and atherosclerotic cardiovascular disease (ASCVD) events. The simulation used a Monte Carlo approach in a representative cohort of German outpatients at high or very-high cardiovascular risk. Additionally to statins, consecutive treatment with ezetimibe, bempedoic acid, and a PCSK9 inhibitor was simulated in patients not achieving their LDL-C goal. Considered were scenarios without and with bempedoic acid (where bempedoic acid was replaced by a PCSK9 inhibitor when LDL-C was not controlled). RESULTS: The simulation cohort consisted of 105,577 patients, of whom 76,900 had very-high and 28,677 high cardiovascular risk. At baseline, 11.2% of patients achieved their risk-based LDL-C target. Sequential addition of ezetimibe and bempedoic acid resulted in target LDL-C in 33.1% and 61.9%, respectively. Treatment with bempedoic acid reduced the need for a PCSK9 inhibitor from 66.6% to 37.8% and reduced drug costs by 35.9% per year on stable lipid-lowering medication. Compared to using only statins and ezetimibe, this approach is projected to prevent additional 6,148 ASCVD events annually per 1 million patients, whereas PCSK9 inhibition alone would prevent 7,939 additional ASCVD events annually. CONCLUSIONS: A considerably larger proportion of cardiovascular high- and very-high-risk patients can achieve guideline-recommended LDL-C goals with escalated lipid-lowering medication. Bempedoic acid is projected to substantially decrease the need for PCSK9 inhibitor treatment to achieve LDL-C targets, associated with reduced drug costs albeit with fewer prevented events.

Cost-Effectiveness Analysis of Dapagliflozin Plus Standard Treatment for Patients With Type 2 Diabetes and High Risk of Cardiovascular Disease in China.

Purpose: To evaluate the long-term cost-effectiveness of dapagliflozin, in addition to standard treatment, for the treatment of adult patients with type 2 diabetes (T2DM) at high cardiovascular risk from the Chinese healthcare system perspective. Methods: A decision-analytic Markov model with one-year cycles was developed to evaluate the health and economic outcomes in patients with T2DM and high risk of cardiovascular disease (CVD) treated with standard treatment and dapagliflozin plus standard treatment for 30 years. Clinical data, cost, and utility data were extracted from databases or published literature. Quality-adjusted life-years (QALYs), costs (€/¥ 2021) as well as incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty in the results. Results: Compared with standard treatment, dapagliflozin plus standard treatment was predicted to result in an additional 0.25 QALYs (12.26 QALYs vs. 12.01 QALYs) at an incremental cost of €4,435.81 (¥33,875.83) per patient. The ICER for dapagliflozin plus standard treatment vs. standard treatment was €17,742.07 (¥135,494.41) per QALY gained, which was considered cost-effective in China compared to three times the GDP per capita in 2021 (€31,809.77/¥242,928). The deterministic and probabilistic sensitivity analyses showed the base-case results to be robust. Conclusions: The study suggests that, from the perspective of the Chinese health system, dapagliflozin plus standard treatment is a cost-effective option for patients with T2DM at high cardiovascular risk. These findings may help clinicians make the best treatment decisions for patients with T2DM at high cardiovascular risk.

Assessment and Mitigation of Cardiovascular Risk for Prostate Cancer Patients: A Review of the Evidence.

Background: Cardiovascular disease (CVD) is a common comorbidity in patients with prostate cancer. In this review, we summarize the published literature on the association of cardiovascular risk with androgen deprivation therapy (ADT) treatment and explore the potential differences between the gonadotropin-releasing hormone (GnRH) agonists and antagonists and the molecular mechanisms that may be involved. We also provide a practical outlook on the identification of underlying CV risk and explore the different stratification tools available. Results: While not definitive, the current evidence suggests that GnRH antagonists may be associated with lower rates of certain CV events vs agonists, particularly in patients with preexisting CVD. Risk reduction strategies such as lifestyle advice, consideration of ADT modality, and comedications may help to reduce CV risk factors and improve outcomes in prostate cancer patients receiving ADT. Conclusions: Given all the data that is currently available, identification of baseline CV risk factors may be key to risk mitigation in patients with prostate cancer receiving ADT.

Cardiovascular Risks of Hydroxychloroquine vs Methotrexate in Patients With Rheumatoid Arthritis.

BACKGROUND: Hydroxychloroquine is often used as a first-line treatment of rheumatoid arthritis despite limited evidence on its cardiovascular risk. OBJECTIVES: We conducted a cardiovascular safety evaluation comparing hydroxychloroquine to methotrexate among patients with rheumatoid arthritis. METHODS: Using Medicare data (2008-2016), we identified 54,462 propensity score-matched patients with rheumatoid arthritis, aged ≥65 years, who initiated hydroxychloroquine or methotrexate. Primary outcomes were sudden cardiac arrest or ventricular arrythmia (SCA/VA) and major adverse cardiovascular event (MACE). Secondary outcomes were cardiovascular mortality, all-cause mortality, myocardial infarction, stroke, and hospitalized heart failure (HF). We also examined treatment effect modification by history of HF. RESULTS: Hydroxychloroquine was not associated with risk of SCA/VA (HR: 1.03; 95% CI: 0.79-1.35) or MACE (HR: 1.07; 95% CI: 0.97-1.18) compared with methotrexate. In patients with history of HF, hydroxychloroquine initiators had a higher risk of MACE (HR: 1.30; 95% CI: 1.08-1.56), cardiovascular mortality (HR: 1.34; 95% CI: 1.06-1.70), all-cause mortality (HR: 1.22; 95% CI: 1.04-1.43), myocardial infarction (HR: 1.74; 95% CI: 1.25-2.42), and hospitalized HF (HR: 1.29; 95% CI: 1.07-1.54) compared to methotrexate initiators. Cardiovascular risks were not different in patients without history of HF except for an increased hospitalized HF risk (HR: 1.57; 95% CI: 1.30-1.90) among hydroxychloroquine initiators. CONCLUSIONS: In older patients with rheumatoid arthritis, hydroxychloroquine and methotrexate showed similar SCA/VA and MACE risks; however, hydroxychloroquine initiators with history of HF had higher risks of MACE, cardiovascular mortality, all-cause mortality, and myocardial infarction. An increased hospitalized HF risk was observed among hydroxychloroquine initiators regardless of an HF history.

Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors Versus Metformin : A Cohort Study.

BACKGROUND: Evidence on the risk for cardiovascular events associated with use of first-line sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared with metformin is limited. OBJECTIVE: To assess cardiovascular outcomes among adults with type 2 diabetes (T2D) who initiated first-line treatment with SGLT-2i versus metformin. DESIGN: Population-based cohort study. SETTING: Claims data from 2 large U.S. commercial and Medicare databases (April 2013 to March 2020). PARTICIPANTS: Patients with T2D aged 18 years and older (>65 years in Medicare) initiating treatment with SGLT-2i or metformin during April 2013 to March 2020, without any use of antidiabetic medications before cohort entry, were identified. After 1:2 propensity score matching in each database, pooled hazard ratios (HRs) and 95% CIs were reported. INTERVENTION: First-line SGLT-2i (canagliflozin, empagliflozin, or dapagliflozin) or metformin. MEASUREMENTS: Primary outcomes were a composite of hospitalization for myocardial infarction (MI), hospitalization for ischemic or hemorrhagic stroke or all-cause mortality (MI/stroke/mortality), and a composite of hospitalization for heart failure (HHF) or all-cause mortality (HHF/mortality). Safety outcomes including genital infections were assessed. RESULTS: Among 8613 first-line SGLT-2i initiators matched to 17 226 metformin initiators, SGLT-2i initiators had a similar risk for MI/stroke/mortality (HR, 0.96; 95% CI, 0.77 to 1.19) and a lower risk for HHF/mortality (HR, 0.80; CI, 0.66 to 0.97) during a mean follow-up of 12 months. Initiators receiving SGLT-2i showed a lower risk for HHF (HR, 0.78; CI, 0.63 to 0.97), a numerically lower risk for MI (HR, 0.70; CI, 0.48 to 1.00), and similar risk for stroke, mortality, and MI/stroke/HHF/mortality compared with metformin. Initiators receiving SGLT-2i had a higher risk for genital infections (HR, 2.19; CI, 1.91 to 2.51) and otherwise similar safety as those receiving metformin. LIMITATION: Treatment selection was not randomized. CONCLUSION: As first-line T2D treatment, initiators receiving SGLT-2i showed a similar risk for MI/stroke/mortality, lower risk for HHF/mortality and HHF, and a similar safety profile except for an increased risk for genital infections compared with those receiving metformin. PRIMARY FUNDING SOURCE: Brigham and Women's Hospital and Harvard Medical School.