Use Of Cardioprotective Medications Research Articles

Abstract PO5-12-03: Cardiovascular Toxicities in Breast Cancer Survivors

Abstract Background: Chemotherapy, despite its effectiveness, presents drawbacks in breast cancer patients due to its side effects. Fatigue, hair loss, nausea, and anemia are among the many symptoms associated with chemotherapy. Moreover, chemotherapy can lead to cardiovascular diseases, including cardiac arrhythmias, hypertension, heart failure, heart attacks, and cardiomyopathy, particularly with the use of anthracyclines and HER-2-targeted agents. Risk factors such as weight, age, race, comorbidities (e.g., obesity, diabetes, hyperlipidemia), and radiation exposure further increase these risks. Despite these potential complications, guidelines are just emerging aiming to prevent these cardiovascular complications in breast cancer patients. Untreated cardiovascular abnormalities can have long-term effects on breast cancer survivors. Our aim is to analyze the relationships between breast cancer treatment and cardiovascular abnormalities, examining associations with various factors, including race, BMI, and age in a majority Hispanic cohort of breast cancer survivors. Methods: retrospective, single institution study data from a total of 53 patients treated with chemotherapy with either anthracyclines and/or HER 2 directed therapy with curative intent between 2018-2020. Our analysis included basic demographic information, menopausal status, breast cancer type, treatment types, use of cardio-protective medications, and cardiovascular effects (both pre-existing and developed during treatment). Results: Our sample of 50 women primarily comprised Hispanic individuals (73%), most of whom were postmenopausal (86%), with an average age of 63 years (range 35-86). Among the breast cancer types identified, 35 were hormone-positive, 8 were HER-2 positive, and 10 were triple negative. 72% of the patients received adjuvant hormonal therapy. 18% of the population received anthracycline-based treatment, 8% received Her 2 directed therapy and 2 % received Immune check point inhibitors. Radiation therapy was administered to 50% of the patients. The most prevalent cardiovascular disease observed was hypertension, affecting 62% of patients, followed by type 2 diabetes (38%), hyperlipidemia (34%), stroke (8%), and heart attack (6%). The predominant cardioprotective medications used were ACE inhibitors/ARBs (48%), followed by statins (46%), beta-blockers (20%), aspirin (16%), and GLP-1 agonists (14%). Conclusion: Our analysis revealed a high prevalence of cardiovascular conditions among breast cancer survivors treated with chemotherapy in a majority Hispanic cohort of patients. This population has been linked to higher risk of developing comorbidities such as diabetes, obesity and hypertension. Further analysis evaluating risk factors and implementation of treatment strategies to minimize adverse effects is needed in this population. Citation Format: Victoria Ayodele, Emily Sherry, Marcela Mazo-Canola. Cardiovascular Toxicities in Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-03.

Estimated risk of cardiovascular events and long-term complications: The projected future of diabetes patients in Delhi from the DEDICOM-II survey

ProblemDespite high prevalence and ethnic susceptibility, limited published estimates are available on long term complication risks among known diabetes patients in India. Hence, we undertook evaluation of the cardiovascular risk of known diabetes patients from Delhi. MethodsThe community-survey was conducted using a probability-proportionate-to-size(systematic) 2-stage cluster design. Thirty areas were selected for a house-to-house survey to recruit 25 to 30 subjects (known diabetes ≥1 year; 35–65 years of age) per area. Scores from the UKPDS 2.1, UKPDS 2.0, Framingham, ASCVD, WHO, NHS and SCORE studies were used for 10-year risk calculation. ResultsWe enrolled 843 subjects of which 800 consented for blood sampling. The mean age of the subjects was 53.0(52.1–54.0) years, the mean duration since diagnosis was 7.1(6.7–7.5) years, with 49.8 % women. 61.8 % were hypertensive, 81.5 % were dyslipidaemic and 53.3 % had poor glycaemic control. Although variable, risk engines estimates were consensual in projecting a high ten-year Coronary-Heart-Disease risk of 10–16 %, a stroke risk of 3.7–5.0 %, and a 5.0–5.7% risk of cardiovascular fatality. These risks were 1.5–3 times the ‘risk at target levels’ suggesting mitigability. Only 9.3 %, 16.0 %, and 30.0 % were taking aspirin, lipid lowering drugs and antihypertensives respectively. ConclusionThe study highlights the impending impact of, and the scope for improvement in the cardiovascular risk profile of diabetes patients in Delhi, including the use of cardioprotective medications. It strengthens the case for developing and testing potential interventions for improvement.

Use of Cardioprotective Antidiabetic Medications in Adults With and Without Cardiovascular Disease, 2015 to March 2020.

Certain glucagon-like peptide-1 receptor (GLP-1) agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2-inhibitors) can reduce cardiovascular risk in individuals with type 2 diabetes and cardiovascular disease (CVD). However, these medications can be expensive, potentially limiting their use. Objectives: The primary objective was to characterize the use of cardioprotective GLP-1 agonists and SGLT2-inhibitors among adults with diabetes with and without CVD. The secondary objective was to investigate the association of socioeconomic factors and health care utilization with the use of these medications. Adults aged ≥20 years old with self-reported diabetes, A1c ≥6.5%, or fasting glucose ≥126 mg/dL were identified using the 2015 to March 2020 National Health and Nutrition Examination Survey. The primary outcome was the use of cardioprotective GLP-1 agonists or SGLT2-inhibitors compared in individuals with and without CVD. Secondary analyses included identification of socioeconomic factors and health care utilization associated with the use of cardioprotective antidiabetic medications, stratified by CVD status. Weighted analyses were conducted to account for the complex survey design. Use of cardioprotective antidiabetic medications was higher in adults with CVD compared to those without CVD (7.8% vs. 4.6%, P = 0.02), which was driven by the use of cardioprotective SGLT2-inhibitors (4.6% versus 1.9%, P = 0.002). Lower income level and less frequent health care visits within the past year were associated with lower likelihood of using these medications. Despite preferential use in individuals with diabetes and CVD, the prevalence of cardioprotective antidiabetic medication use remains relatively low. Disparities in use appear to exist based on income level and health care utilization.

Medication use by insurance coverage in subjects with coronary heart disease in the Southern Cone of Latin America

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) grant number HHSN268200900029C. Background Clinical guidelines recommend cardioprotective medication use in coronary heart disease (CHD) patients. Underuse of these drugs is common among patients of low resources, which may be explained by insufficient access in the public sector. Aim We aim to assess medication use and barriers to care by insurance coverage in subjects with CHD in the Southern Cone of Latin America. Methods We analysed cross-sectional data from 593 participants with CHD residing in Argentina, Chile and Uruguay, within the CESCAS community-based cohort study. Participants were categorized as covered by public insurance only or having additional coverage (social security or private insurance). We calculated the prevalence of recommended medications use, mean number of medications, use of ≥ 1 and ≥ 2 drugs, and reported barriers to needed care in insured and uninsured participants. Differences between coverage groups were assessed with univariable and multivariable analysis (logistic and Poisson regression) adjusted by age, sex, previous revascularization, educational level and barriers. Results Medication use ranged from 39.8% (lipid-lowering) to 84.1% (antihypertensives). Mean number of medications was 1.8 (SE 0.1), 95.4% used ≥ 1 drugs, and 59.8% used ≥ 2 drugs. There were no significant differences by coverage in medication use, except for higher ACE-inhibitor and nitrate use among participants in the public sector (35.8% vs. 53.2%, p=0.001; and 1.5% vs. 5.2%, p=0.047 respectively). In the multivariable analysis, having public coverage only was not significantly associated with medication use, but it was with reporting barriers to care (OR 2.06, 95% CI 1.21-3.52). Conclusion Insurance coverage was not associated with the use of most medications in CHD patients in the Southern Cone of Latin America, possibly due to public health programs providing them free of charge. Uninsured participants more often face barriers to access medical care, and future studies should address these healthcare inequalities.

Prevalence of Cardioprotective Medication Use in Coronary Heart Disease Patients in South America: Systematic review and Meta-Analysis.

Background:Coronary heart disease (CHD) is the most common cause of death globally, and clinical guidelines recommend cardioprotective medications for patients with established CHD. Suboptimal use of these medications has been reported, but information from South America is scarce.Methods:We conducted a systematic review on prevalence of secondary prevention medication in South America. We pooled prevalence estimates, analysed time-trends and guideline compliance, and identified factors associated with medication use with meta-regression models.Results:73 publications were included. Medication prevalence varied by class: beta-blockers 73.4%(95%CI 66.8%–79.1%), ACEI/ARBs 55.8%(95%CI 49.7%–61.8), antiplatelets 84.6%(95%CI 79.6%–88.5%), aspirin 85.1%(95%CI 79.7%–89.3%) and statins 78.9%(95%CI 71.2%–84.9%). The use of beta-blockers, ACEI/ARBs and statins increased since 1993. Ten publications reported low medication use and nine reported adequate use. Medication use was lower in community, public and rehabilitation settings compared to tertiary centres.Conclusion:Cardioprotective medication use has increased, but could be further improved particularly in community settings.

Prevalence of cardioprotective medication use in coronary heart disease patients in South America: systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Coronary heart disease (CHD) is the most common cause of death globally, and clinical guidelines recommend cardioprotective medications for patients with established CHD. Suboptimal use of these medications has been reported, but an overview from the South American region is lacking. Purpose Our aim is to summarize evidence on the prevalence of cardioprotective medication use for secondary prevention of CHD in South America. We also intend to explore time-trends, guideline compliance and factors associated with medication use. Methods We conducted a systematic review searching literature in PubMed, Embase, Cochrane, Lilacs and SciElo. We searched articles published from 2000 to 2021 that reported prevalence of secondary prevention medication use in South America. We pooled the prevalence estimates in a meta-analysis, described findings on guideline compliance, and used meta-regression models to analyse time-trends and identify factors associated with medication use. Results We identified 7388 publications, from which 73 were included in the review (Fig 1). Medication prevalence varied by class: beta-blockers 73.0%(95%CI 66.6%–79.1%), ACEI/ARBs 55.8% (95%CI 49.7%–61.8), antiplatelets 84.6% (95%CI 79.6%–88.5%), acetylsalicylic acid 85.1% (95%CI 79.7%–89.3%) and statins 78.5% (95%CI 70.7%–84.7%). Heterogeneity of the pooled estimates was high. Ten publications reported low medication use and nine reported adequate use. The use of beta-blockers, ACEI/ARBs and statins significantly increased from 1993 to 2020. Medication use was lower in community, public and rehabilitation settings compared to tertiary centres. Conclusion The use of most cardioprotective medication classes for secondary prevention of CHD in South America has increased over the last 20 years, but it could be further improved particularly in community settings.

Diagnostic features, management and prognosis of type 2 myocardial infarction compared to type 1 myocardial infarction: a systematic review and meta-analysis

ImportanceDistinguishing type 2 (T2MI) from type 1 myocardial infarction (T1MI) in clinical practice can be difficult, and the management and prognosis for T2MI remain uncertain.ObjectiveTo compare precipitating factors, risk factors,...

Comparing pharmacotherapy in MINOCA versus medically managed obstructive acute coronary syndrome.

Most prior studies have compared myocardial infarction with non-obstructive coronary arteries (MINOCA), to obstructive acute coronary syndrome (ACS) often requiring revascularisation. However, these were subject to treatment bias given the significant differences in management. This study uniquely compares the management and outcomes of MINOCA patients with a medically managed obstructive ACS (M-ACS) population. We retrospectively analysed registry data for consecutive patients admitted to the Gold Coast University Hospital with ACS requiring coronary angiography and identified patients with MINOCA and M-ACS. Baseline characteristics, pharmacological therapy and in-hospital outcomes were compared. In hospital outcomes were composite NACE, heart failure, stroke and major bleeding. Multivariate regression analysis was also performed to identify independent predictors of MINOCA. Multivariate regression analysis was also performed to identify independent predictors of MINOCA. We identified 139 patients with MINOCA and 142 patients with medically managed obstructive ACS (M-ACS). Multivariate regression analysis also identified female sex and cancer as independent predictors of MINOCA with odds ratios of 5.57 and 3.01, respectively. MINOCA patients were significantly less likely to receive cardioprotective medications at admission and discharge, specifically aspirin, beta-blockers, ACE-I and statins, compared to those with M-ACS. While mortality was higher among M-ACS patients (0.0% vs. 3.6%; p = 0.03), no significant differences were noted for composite NACE, heart failure, stroke and major bleeding. MINOCA patients have similar outcomes to M-ACS. Despite this, we noted a discrepancy in the use of cardioprotective medications. We also identified female sex and cancer were independent predictors of MINOCA. This may represent a missed opportunity to prevent adverse events among patients with MINOCA. Large, randomised trials are required to provide more definitive evidence.

Trends in Use of Cardioprotective Medication in Peripheral Artery Disease: A Nationwide Study.

BackgroundGuideline‐based cardioprotective medical therapy is intended to reduce the burden of adverse cardiovascular and limb outcomes in patients with peripheral artery disease (PAD). However, contemporary data describing trends in use of medication remains limited. The present study, therefore, aims to investigate changes in use of cardioprotective medication in PAD.Methods and ResultsBy using Danish national healthcare registries, we identified all patients with first‐time diagnosis of PAD (1997–2016) and classified them into two groups: (1) PAD+ that includes all patients with PAD with a history of cardiovascular disease, ie, myocardial infarction, atrial fibrillation, and stroke (n=162 627); and (2) PAD (n=87 935) that comprise patients without a history of cardiovascular disease. We determined the use of medication in the first 12 months after the incident diagnosis of PAD and estimated age standardized 1‐year mortality rates. Our results showed increase in use of cardioprotective medication throughout the study period in both groups. However, PAD+ had a higher use of medication (acetylsalicylic acid, 3.5%–48.4%; Clopidogrel, 0%–17.6%; vitamin K antagonists, 0.9%–7.8%; new oral anticoagulants, 0.0%–10.1%; Statins, 1.9%–58.1%; angiotensin‐converting enzyme inhibitors, 1.2%–20.6%), compared with PAD (acetylsalicylic acid, 2.9%–54.4%; Clopidogrel, 0%–11.9%; vitamin K antagonists, 0.9%–2.4%; new oral anticoagulants, 0.0%–3.4%; Statins, 1.5%–56.9%; angiotensin‐converting enzyme, 0.9%–17.2%), respectively. Furthermore, 1‐year mortality rates in PAD declined with increased use of medications during study.ConclusionsIn this nationwide study, use of cardioprotective medication increased considerably with time, but compared to patients with other atherosclerotic diseases, there remains an underuse of guideline‐based medical therapy in patients with PAD.

Poor adherence to lifestyle recommendations in patients with coronary heart disease: results from the EUROASPIRE surveys.

Despite the high use of cardioprotective medications, the risk factor control in patients with coronary heart disease (CHD) is still inadequate. Guidelines identify healthy lifestyles as equally important in secondary prevention as pharmacotherapy. Here, we describe reasons for poor lifestyle adherence from the patient's perspective. In the EUROASPIRE IV and V surveys, 16 259 CHD patients were examined and interviewed during a study visit ≥6 months after hospital discharge. Data gathering was fully standardized. The Brief Illness Perception questionnaire was completed by a subsample of 2379 patients. Half of those who were smoking prior to hospital admission, were still smoking; 37% of current smokers had not attempted to quit and 51% was not considering to do so. The prevalence of obesity was 38%. Half of obese patients tried to lose weight in the past month and 61% considered weight loss in the following month. In relation to physical activity, 40% was on target with half of patients trying to do more everyday activities. Less than half had the intention to engage in planned exercise. Only 29% of all patients was at goal for all three lifestyle factors. The number of adverse lifestyles was strongly related to the way patients perceive their illness as threatening. Lifestyle modifications were more successful in those having participated in a cardiac rehabilitation and prevention programme. Patients indicated lack of self-confidence as the main barrier to change their unhealthy behaviour. Modern secondary prevention programmes should target behavioural change in all patients with adverse lifestyles.

Risk of cardiovascular disease among women carrying BRCA mutations after risk-reducing bilateral salpingo-oophorectomy: A population-based study

ObjectiveExamine the risk of cardiovascular disease (CVD) following risk reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA mutations. MethodsIn this retrospective population-based study in British Columbia, Canada, between 1996 and 2017, we compared the risk of CVD among women with known BRCA mutations who underwent RRBSO before the age of 50 (n = 360) with two groups of age-matched women without known BRCA mutations: 1) women who underwent bilateral oophorectomy (BO) for benign conditions (n = 3600); and, 2) women with intact ovaries who had hysterectomy or salpingectomy (n = 3600). Our primary outcome was CVD (a composite (any of) myocardial infarction, heart failure, and/or cerebrovascular disease). Secondary outcomes included a diagnostic code for predisposing conditions (hypertension, dyslipidemia, and/or diabetes mellitus), and use of cardioprotective medications (statins and/or beta-blockers). ResultsWe report no significant increased risk for CVD between women with BRCA mutations and women who underwent BO (aHR = 1.08, 95%CI: 0.72–1.62), but women with BRCA mutations were less likely to be diagnosed with predisposing conditions (aHR = 0.69, 95%CI: 0.55–0.85). Compared to women without BRCA mutations with intact ovaries who underwent hysterectomy or salpingectomy, women with BRCA mutations had significantly increased risk for CVD (aHR = 1.82, 95%CI: 1.18–2.79) and were less likely to be diagnosed with predisposing conditions (aHR = 0.78, 95%CI: 0.62–0.97) and to fill cardioprotective medications (aHR = 0.88, 95%CI: 0.64–1.22). ConclusionOur results suggest an opportunity for improved prevention of CVD in women with BRCA mutations after prophylactic oophorectomy. Despite the observed lower prevalence of predisposing conditions for CVD and lesser use of cardioprotective medications, this population did not have a lower rate of CVD.

CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

BackgroundThe CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts.ObjectivesThis study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment.MethodsWe recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA).ResultsBreast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups.ConclusionsCBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

Abstract PS13-21: Cardiac function in patients receiving trastuzumab for HER2+ metastatic breast cancer with left ventricular ejection fraction<50% at baseline

Abstract Research objectives and rationale Trastuzumab greatly enhances the efficacy of treatment in HER2+ metastatic breast cancer (MBC). Due to its potential to induce cardiomyopathy, however, trastuzumab is contraindicated in patients with baseline left ventricular ejection fraction (LVEF) <50%, although this criterion is sometimes waived. We investigated the effect of trastuzumab on the cardiac function in a real-world cohort of patients with HER2+ MBC with a reduced baseline LVEF, i.e. baseline LVEF <50%. Methods We collected data on patients with HER2+ MBC who received at least one cycle of trastuzumab-based treatment between 2000 and 2014 in eight Dutch hospitals. Eligible patients had baseline LVEF 40-50%. Data were retrospectively collected from medical files using case record forms. Primary endpoint was severe cardiotoxicity defined as LVEF <40%. We also investigated whether severe cardiotoxicity was reversible. Reversibility was defined as any LVEF increase to a value <5% below baseline value and irreversibility as any absolute LVEF increase <10% from lowest value to >5% below baseline. Exploratory, we compared the incidence of severe cardiotoxicity in patients with and without cardioprotective medication at start trastuzumab. Results Of the 758 patients identified with HER2+ MBC, 41 patients were included with a LVEF <50% at start of trastuzumab treatment. The median LVEF at start was 46% with an interquartile range (IQR) of 42-48%. The median duration of trastuzumab treatment was 14 months (IQR 8-32 months). During this period, 16 patients (39%) developed severe cardiotoxicity. The median time to severe cardiotoxicity was 7 months (IQR 4-10 months). Severe cardiotoxicity was reversible in 6 patients (43%), partly reversible in 4 patients (29%) and irreversible in 4 patients (29%). Two patients were lost-to-follow-up. Of the 6 patients with reversible severe cardiotoxicity, trastuzumab treatment was continued in 2 patients (33%), interrupted <6 months in 1 patient (17%) and discontinued in 3 patients (50%). Of the 4 patients with irreversible severe cardiotoxicity, trastuzumab treatment was interrupted in 1 patient (25%) and discontinued in the other 3 patients (75%). In total, 12 patients (29%) received cardioprotective medications, i.e. beta-blocker (n=4), ACE inhibitor (n=4) or both (n=4), at start of trastuzumab treatment. In patients who received cardioprotective medications at start trastuzumab severe cardiotoxicity was less often observed compared to patients who did not received cardioprotective medications at start of trastuzumab (17% vs 48%, p=0.059, Table). Conclusion In our cohort of patients with HER2+ MBC, trastuzumab could be safely administered in 61% without developing severe cardiotoxicity despite an impaired LVEF at the start of trastuzumab treatment. Severe cardiotoxicity was (partly) reversible in about two thirds of the cases. Risks and benefits of trastuzumab use in this vulnerable population must be balanced carefully. The use of cardioprotective medications at start of trastuzumab treatment might reduce the risk of developing severe cardiotoxicity. Clinical characteristics of patients with and without cardioprotective medication from start trastuzAll patients (n=41)Patients with cardioprotective medication from start trastuzumab (n=12)Patients without cardioprotective medication fromStart trastuzumab (n=29)P-valueSevere cardiotoxicitya, n (%)16 (39)2 (17)14 (48)0.059Time to cardiotoxicity, months [IQR]7 [3 - 12]6 [not reached - 8]8 [4 - 11]0.515Reversibilityb, n (%)No4 (29)1 (8)3 (10)0.260Partial4 (29)0 (0)4 (14)Yes6 (43)0 (0)6 (21)Trastuzumab treatment , n (%)Continued27 (66)7 (58)20 (69)0.796Interrupted6 (15)2 (17)4 (14)Discontinued8 (20)3 (25)5 (17)LVEF, median % (IQR)Baseline46 [42 - 48]47 [44 - 49]46 [43 - 48]0.177Nadir42 [33 - 45]43 [40 - 47]40 [32 - 45]0.322Highest53 [50 - 57]52 [50 - 57]53 [49 - 58]0.761Difference nadir and highest13 [9 - 20]11 [7 - 19]13 [10 - 21]0.464Cardiac symptoms, n (%)16 (39)4 (33)12 (41)0.515 Citation Format: Nathalie I Bouwer, Tessa G Steenbruggen, Hanah N Rier, Jos JEM Kitzen, Carolien H Smorenburg, Marlies L Van Bekkum, Albert J Ten Tije, Paul C De Jong, Jan C Drooger, Cynthia Holterhues, Marcel JM Kofflard, Eric Boersma, Gabe S Sonke, Mark-David Levin, Agnes Jager. Cardiac function in patients receiving trastuzumab for HER2+ metastatic breast cancer with left ventricular ejection fraction<50% at baseline [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-21.

Long-term health outcomes of people with reduced kidney function in the UK: A modelling study using population health data.

People with reduced kidney function have increased cardiovascular disease (CVD) risk. We present a policy model that simulates individuals' long-term health outcomes and costs to inform strategies to reduce risks of kidney and CVDs in this population. We used a United Kingdom primary healthcare database, the Clinical Practice Research Datalink (CPRD), linked with secondary healthcare and mortality data, to derive an open 2005-2013 cohort of adults (≥18 years of age) with reduced kidney function (≥2 measures of estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 ≥90 days apart). Data on individuals' sociodemographic and clinical characteristics at entry and outcomes (first occurrences of stroke, myocardial infarction (MI), and hospitalisation for heart failure; annual kidney disease stages; and cardiovascular and nonvascular deaths) during follow-up were extracted. The cohort was used to estimate risk equations for outcomes and develop a chronic kidney disease-cardiovascular disease (CKD-CVD) health outcomes model, a Markov state transition model simulating individuals' long-term outcomes, healthcare costs, and quality of life based on their characteristics at entry. Model-simulated cumulative risks of outcomes were compared with respective observed risks using a split-sample approach. To illustrate model value, we assess the benefits of partial (i.e., at 2013 levels) and optimal (i.e., fully compliant with clinical guidelines in 2019) use of cardioprotective medications. The cohort included 1.1 million individuals with reduced kidney function (median follow-up 4.9 years, 45% men, 19% with CVD, and 74% with only mildly decreased eGFR of 60-89 mL/min/1.73 m2 at entry). Age, kidney function status, and CVD events were the key determinants of subsequent morbidity and mortality. The model-simulated cumulative disease risks corresponded well to observed risks in participant categories by eGFR level. Without the use of cardioprotective medications, for 60- to 69-year-old individuals with mildly decreased eGFR (60-89 mL/min/1.73 m2), the model projected a further 22.1 (95% confidence interval [CI] 21.8-22.3) years of life if without previous CVD and 18.6 (18.2-18.9) years if with CVD. Cardioprotective medication use at 2013 levels (29%-44% of indicated individuals without CVD; 64%-76% of those with CVD) was projected to increase their life expectancy by 0.19 (0.14-0.23) and 0.90 (0.50-1.21) years, respectively. At optimal cardioprotective medication use, the projected health gains in these individuals increased by further 0.33 (0.25-0.40) and 0.37 (0.20-0.50) years, respectively. Limitations include risk factor measurements from the UK routine primary care database and limited albuminuria measurements. The CKD-CVD policy model is a novel resource for projecting long-term health outcomes and assessing treatment strategies in people with reduced kidney function. The model indicates clear survival benefits with cardioprotective treatments in this population and scope for further benefits if use of these treatments is optimised.

Abstract PO-098: Cardioprotective medication use in hormone receptor positive breast cancer survivors

Abstract Introduction: Cardiovascular diseases (CVD), including treatment-related cardiotoxicity, are problematic for breast cancer survivors, particularly Black women. Prevention and management of CV-related morbidity, including uptake of cardioprotective medication such as angiotensin converting enzyme inhibitors (ACEi) or ß-Blocker (BB), is a priority for many breast cancer survivors. We assessed the prevalence of cardioprotective medication use in survivors and identified factors associated with use by race. Methods: This was a secondary analysis of data from the Women’s Hormonal Initiation and Persistence (WHIP) study, a longitudinal observational trial of women diagnosed with hormone receptor positive breast cancer prescribed adjuvant endocrine therapy. The primary outcome, ACEi/BB use was dichotomized as yes versus no and based on pharmacy records. Demographic, psychosocial (e.g. discrimination), healthcare (e.g. provider communication), and quality of life factors (e.g. functional well-being) were collected from patient surveys. Clinicopathologic variables were abstracted from medical records. Bivariate associations by race and ACEi/BB use were assessed using chi square and t-tests while three logistic regression analyses were used assess multivariable associations between predictors and ACEi/BB use in all women and stratified by race. Results: Of the 246 survivors, 33.3% were Black, 58.4% were &amp;lt;65 years of age, and 64.3%.3% were diagnosed with stage I disease. Fifty-seven percent of women had hypertension and 33.3% received ACEi/BBs. In bivariate analysis, ACEi/BB use was significantly more common among Black women, those with hypertension, and women who experienced discrimination. In unadjusted logistic regression models, White women (vs. Black) (OR: 0.33, 95% CI: 0.19-0.58) and women with higher ratings of functional wellbeing (OR: 0.94, 95% CI: 0.89-0.00) were less likely to use ACEi/BBs. Women ≥65 and those with hypertension were more likely to use ACEi/BBs. Satisfaction with provider communication was a significant predictor of medication use for White women. In logistic regression models adjusted for age and race, race was not associated with ACEi/BB use (OR: 0.50, 95% CI: 0.21-1.17). Odds of ACEi/BB use were highest amongst women with hypertension and, for Black women only, in women &amp;gt;65. Conclusions: CVD contributes to poorer outcomes in breast cancer survivors, particularly in Black women. Future studies on CVD management and prevention practices and the roles of psychosocial and healthcare factors on ACEi/BB adherence are warranted. Citation Format: Arnethea L. Sutton, Ashley S. Felix, Vanessa B. Sheppard. Cardioprotective medication use in hormone receptor positive breast cancer survivors [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-098.

Time trends in use of cardioprotective medication in patients with peripheral artery disease between 1997 and 2016: a nationwide study

Abstract Background Peripheral artery disease (PAD) is associated with increased cardiovascular (CV) morbidity and mortality. Aggressive management of risk factors and lifestyle modification may improve outcomes for patients with PAD. The present study aims to investigate changes in use of cardioprotective medication after the incident diagnosis of PAD between 1997 and 2016. Methods By using Danish national healthcare registries, we identified all patients with first-time diagnosis of PAD between 1997 and 2016. These patients were classified into 2 main groups: PAD-all (n=167,762) that includes all PAD patients with or without a history of CVD, including myocardial infarction (MI), atrial fibrillation (AF), and stroke (n=167,761) and PAD-only (n=87,935) that comprise patients with PAD without a history of AF, MI, and stroke. We calculated temporal trends and assessed comparative use of cardioprotective medication in the first 12 months after the incident diagnosis of PAD. Results Our results showed an improved use of cardioprotective medication temporally in both groups. However, PAD-all were marginally better treated (Aspirin, 3.5% - 48.4%; Clopidogrel, 0% - 17.6%; VKA 0.9% - 7.8%; NOACs 0.0% - 10.1%; Statins, 1.9%- 58.1%; ACE-inhibitors, 1.2% - 20.6%), compared to PAD-only (Aspirin, 2.9% - 54.4%; Clopidogrel, 0% - 11.9%; VKA 0.9% - 2.4%; NOACs 0.0% - 3.4%; Statins, 1.5%- 56.9%; ACE-inhibitors, 0.9% - 17.2%), respectively. Proportion of PAD patients treated with any cardioprotective medication was greater among those with a history of MI or stroke. Whereas, PAD patients with a history of AF were substantially better treated with VKA and NOACs. Conclusion In this nationwide study, use of cardioprotective medication increased considerably with time, but there remains an underuse of guideline-recommended therapy in patients with PAD. Funding Acknowledgement Type of funding source: None

Medical Treatment in Coronary Patients: Is there Still a Gender Gap? Results from European Society of Cardiology EUROASPIRE V Registry.

This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). Analyses were based on the ESC EORP EUROASPIRE V (European Survey Of Cardiovascular Disease Prevention And Diabetes) survey. Consecutive patients between 18 and 80years, hospitalized for a coronary event, were included in the study. Information on cardiovascular medication intake at hospital discharge and at follow-up (≥ 6months to < 2years after hospitalization) was collected. Data was available for 8261 patients (25.8% women). Overall, no gender differences were observed in the prescription and use of cardioprotective medication like aspirin, beta-blockers, and ACE-I/ARBs (P > 0.01)at discharge and follow-up respectively. However, a statistically significant difference was found in the use of statins at follow-up, in disfavor of women (82.8% vs. 77.7%; P < 0.001). In contrast, at follow-up, women were more likely to use diuretics (31.5% vs. 39.5%; P < 0.001) and calcium channel blockers (21.2% vs. 28.8%; P < 0.001), whereas men were more likely to use anticoagulants (8.8% vs. 7.0%; P < 0.001). Overall, no gender differences were found in total daily dose intake (P > 0.01). Furthermore, women were less likely than men to have received a CABG (20.4% vs. 13.2%; P < 0.001) or PCI (82.1% vs. 74.9%; P < 0.001) at follow-up. No gender differences were observed in prescribed (P = 0.10) and attended (P = 0.63) cardiac rehabilitation programs. The EUROASPIRE V results show only limited gender differences in the medical management of CHD patients. Current findings suggest growing awareness aboutrisk in female CHD patients.

Effects of GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Heart Transplant Patients with Type 2 Diabetes: a Case Series

Background Type 2 diabetes mellitus (T2D) is common in post-heart transplant patients. Commonly used T2D medications, especially insulin, can promote weight gain and are not associated with cardiovascular (CV) benefits. Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) are two drug classes that produce CV benefits in T2D and promote weight loss with minimal risk of hypoglycemia. Their use has not been previously evaluated in this particular group, and there have been theoretical concerns about safety in immunosuppressed patients. Methods Patients with T2D are sequentially referred by the Heart Transplant program to the Cardiometabolic Center of Excellence (CMCE) at our institution, allowing minimal selection bias. CMCE provides treatment algorithms that emphasize the use of cardioprotective T2D medications. We analyzed this initial series of transplant patients with T2D who have been on GLP-1 RA and/or SGLT-2i with at least two visits at CMCE. Results Among 15 patients, the mean age was 59.4 ± 2.6 years, 66.7% were males, 73.3% were Caucasians, 33.3% had history of ischemic cardiomyopathy and baseline eGFR was 53.5 ± 7.9 mL/min/1.73m2. The median time from transplant was 4.6 (1.6 - 10.5) years. The median follow-up time at CMCE was 5.4 (2.8 - 10.9) months. At baseline, 73% were on insulin, 40% on Metformin, 13% on Sulfonylurea, 13% on Dipeptidyl peptidase-4 inhibitors, and 7% on Thiazolidinediones. Following initiation of therapy at CMCE, 86.7% of patients were on a combination of GLP-1 RA and SGLT-2i, while the rest were taking only GLP-1 RA. Overall, the median total daily insulin requirements decreased substantially from 94 (40.5 - 124) to 34 (5 - 60) units at latest clinic visit; p = 0.003. Further, median hemoglobin A1c dropped from 7.7% (7.3 - 9.5) to 6.6% (6 - 8.5); p = 0.007. There was also a significant reduction in mean body weight (241.9 ± 35.8 at baseline vs. 217.1 ± 34.2 lbs at follow-up; p = 0.001), and mean body mass index (34.9 ± 4.5 vs. 31.1 ± 3.7; p = 0.001). Only one patient experienced side effects as one episode of severe nausea with Liraglutide that resolved when switched to Semaglutide. No infectious complications (including urinary tract or genital mycotic infections) were observed. Conclusions In this limited case series, combination therapy with GLP-1 RA and SGLT-2i was well tolerated in heart transplant patients and associated with favorable results in insulin requirement, hemoglobin A1c, and body weight. Type 2 diabetes mellitus (T2D) is common in post-heart transplant patients. Commonly used T2D medications, especially insulin, can promote weight gain and are not associated with cardiovascular (CV) benefits. Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) are two drug classes that produce CV benefits in T2D and promote weight loss with minimal risk of hypoglycemia. Their use has not been previously evaluated in this particular group, and there have been theoretical concerns about safety in immunosuppressed patients. Patients with T2D are sequentially referred by the Heart Transplant program to the Cardiometabolic Center of Excellence (CMCE) at our institution, allowing minimal selection bias. CMCE provides treatment algorithms that emphasize the use of cardioprotective T2D medications. We analyzed this initial series of transplant patients with T2D who have been on GLP-1 RA and/or SGLT-2i with at least two visits at CMCE. Among 15 patients, the mean age was 59.4 ± 2.6 years, 66.7% were males, 73.3% were Caucasians, 33.3% had history of ischemic cardiomyopathy and baseline eGFR was 53.5 ± 7.9 mL/min/1.73m2. The median time from transplant was 4.6 (1.6 - 10.5) years. The median follow-up time at CMCE was 5.4 (2.8 - 10.9) months. At baseline, 73% were on insulin, 40% on Metformin, 13% on Sulfonylurea, 13% on Dipeptidyl peptidase-4 inhibitors, and 7% on Thiazolidinediones. Following initiation of therapy at CMCE, 86.7% of patients were on a combination of GLP-1 RA and SGLT-2i, while the rest were taking only GLP-1 RA. Overall, the median total daily insulin requirements decreased substantially from 94 (40.5 - 124) to 34 (5 - 60) units at latest clinic visit; p = 0.003. Further, median hemoglobin A1c dropped from 7.7% (7.3 - 9.5) to 6.6% (6 - 8.5); p = 0.007. There was also a significant reduction in mean body weight (241.9 ± 35.8 at baseline vs. 217.1 ± 34.2 lbs at follow-up; p = 0.001), and mean body mass index (34.9 ± 4.5 vs. 31.1 ± 3.7; p = 0.001). Only one patient experienced side effects as one episode of severe nausea with Liraglutide that resolved when switched to Semaglutide. No infectious complications (including urinary tract or genital mycotic infections) were observed. In this limited case series, combination therapy with GLP-1 RA and SGLT-2i was well tolerated in heart transplant patients and associated with favorable results in insulin requirement, hemoglobin A1c, and body weight.

Suboptimal Use of Cardioprotective Medications in Patients With a History of Cancer

Modern cancer therapies have led to improved survival rates for many cancers. Rates of cardiovascular diseases (CVD) and risk factors are increased in cancer patients and survivors compared with the general population, and CVD has emerged as a leading cause of long-term morbidity and mortality in

Abstract 254: Predictors of Immune Checkpoint Inhibitor Associated Cardiotoxicity

Background: Immune checkpoint inhibitors (ICIs), including programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1) and cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitors, are increasingly used in treatment of advanced stage cancers due to a well-established mortality benefit. ICI therapy is associated with immune mediated toxicity which may impact any organ system. Cardiovascular toxicities are rare based on existing data, but associated with high mortality rates. Objectives: The aim of this study is to determine whether preexisting cardiac conditions and/or cardiac therapies are associated with an increased or decreased risk of developing cardiotoxicity after ICI exposure. Methods: All patients treated with ICI therapy from March 2011 through October 2019 at our institution were identified. Demographic information, treatment dates, pre-treatment cardiac conditions and comorbidities, cancer types, pre-treatment cardiac biomarkers, and pre-treatment cardio-protective medication use were determined for each patient. New cardiac diagnoses after ICI exposure were identified in the medical record. Multivariate logistic regression was used determine the association between preexisting cardiac conditions and/or cardiac therapies and the development of cardiotoxicity after ICI exposure. Results: There were 902 patients identified with 1071 ICI exposures. The majority of exposures were to a PD-1 inhibitor (70%), with the most common drugs being pembrolizumab (42.8%) and nivolumab (26.5%). Eighty-nine new cardiac diagnoses were coded after initiation of ICI therapy. Sixteen events occurred within 30 days of initial exposure to an ICI and likely represent new cases of immune checkpoint inhibitor associated cardiotoxicity (incidence 1.5%). Of these events, one was confirmed as myocarditis, seven were heart failure without confirmation of myocarditis, three were arrhythmia, one was pericarditis, three were myocardial infarction and one was ventricular tachyarrhythmia/sudden cardiac death, without confirmed myocarditis or heart failure. There was an additional case of myocarditis identified within 90 days of initial exposure to ICI therapy, and a third case identified 115 days following exposure. All three patients who developed myocarditis died, consistent with the known high mortality rate of ICI associated myocarditis. One of the patients who developed myocarditis received pembrolizumab, one nivolumab and one cemiplimab (all PD-1 inhibitors). A history of heart failure increased the odds of developing a cardiac toxicity by 2.3 fold (95% CI 1.4 to 3.3, p&lt;0.001) and prior beta-blocker exposure decreased the odds by 1.8 fold (95% -2.9 to -0.7, p=0.002). Conclusion: A history of heart failure is associated with an increased odds of developing cardiotoxicity after ICI exposure while prior beta blocker exposure appears to be protective.