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PURPOSE OF REVIEW: To provide perspective on the current development status, and potential future role, of obicetrapib, a third-generation cholesterylester transfer protein (CETP) inhibitor. Obicetrapib has received recent attention following positive Phase II clinical trial data and initiation of Phase III trials for the treatment of dyslipidemia and atherosclerotic cardiovascular disease (ASCVD). RECENT FINDINGS: The ROSE and ROSE2 trials are Phase II studies that examined the lipid lowering effects of obicetrapib in patients on pre-existing high-intensity statin therapy. Obicetrapib significantly reduced key dyslipidemia biomarkers including low density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) while increasing high-density lipoprotein cholesterol (HDL-C). Four phase III clinical trials, including a cardiovascular outcomes trial, are ongoing. Preliminary data for obicetrapib shows favorable effects on dyslipidemia, which could theoretically lead to a decrease in ASCVD clinical events. Short-term safety data in preliminary studies shows no significant safety signals.
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In this cross-sectional study, we evaluated the completeness, readability, and syntactic complexity of cardiovascular disease prevention information produced by GPT-4 in response to 4 kinds of prompts.
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Enfermedades Cardiovasculares , Estudios Transversales , Humanos , LenguajeRESUMEN
BACKGROUND: There remains uncertainty regarding optimal primary atherosclerotic cardiovascular disease (ASCVD) prevention practices for older adults. OBJECTIVE: To assess statin treatment patterns and incident ASCVD among older patients for primary prevention across the spectrum of ASCVD risk. DESIGN: Retrospective cohort study of participants without ASCVD aged 65-79 years. Patients were stratified by age (65-69, 70-75, > 75 years) and 10-year ASCVD risk category (low/borderline, intermediate, high) based on the Pooled Cohort Equations. Multivariable logistic regressions were used to identify predictors of moderate- or high-intensity statin prescriptions. Cox proportional models were used to estimate hazard ratios (HRs) for incident ASCVD. PARTICIPANTS: Patients aged 65-79 years without ASCVD from a Northern California health system. MAIN MEASURES: Statin prescriptions and incident ASCVD events. KEY RESULTS: There were 54,066 patients, with 10,288 (19%) aged > 75 years and 57% women. Compared with younger groups, adults > 75 years were less likely to be prescribed moderate- or high-intensity statin prescriptions across ASCVD risk groups (all p < 0.001); this persisted after multivariable adjustment including for ASCVD risk (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.74-0.86). Adults > 75 years were more likely to experience incident ASCVD (HR 1.42, 95% CI 1.23-1.63). Women (OR 0.85, 95% CI 0.81-0.89) and underweight older adults (OR 0.45, 95% CI 0.33-0.61) were also less likely to receive moderate- or high-intensity statins. CONCLUSIONS: Among older adults aged 65-79 years without prior ASCVD, those > 75 years of age were less likely to receive moderate- or high-intensity statins regardless of ASCVD risk compared with their younger counterparts, while experiencing more incident ASCVD. Efforts are warranted to study the reasons for age-based differences in statin use in older adults, particularly those at highest ASCVD risk.
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Aterosclerosis , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Anciano , Aterosclerosis/prevención & control , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Prevención Primaria , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE OF THE REVIEW: Despite marked progress in cardiovascular disease management in the last several decades, there remain significant, persistent disparities in cardiovascular health in historically marginalized racial and ethnic groups. Here, we outline current state of health disparities in cardiovascular disease, discuss the interplay between social determinants of health, structural racism, and cardiovascular outcomes, and highlight strategies to address these issues. RECENT FINDINGS: Across the continuum of atherosclerotic cardiovascular disease (ASCVD) prevention, there remain significant disparities in outcomes including morbidity and mortality by race, ethnicity, and socioeconomic status (SES). These disparities begin early in childhood (primordial prevention) and continue with a higher prevalence of cardiovascular risk factors (primary prevention), and in the uptake of evidence-based therapies (secondary prevention). These disparities are driven by social determinants of health and structural racism that disproportionately disadvantage historically marginalized populations. Structural racism and social determinants of health contribute to significant disparities in cardiovascular morbidity and mortality.
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Aterosclerosis , Enfermedades Cardiovasculares , Disparidades en el Estado de Salud , Aterosclerosis/etnología , Enfermedades Cardiovasculares/etnología , Etnicidad/estadística & datos numéricos , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Determinantes Sociales de la SaludRESUMEN
BACKGROUND: Lipoprotein(a) (Lp(a)) is a highly proatherogenic lipid fraction that is a clinically significant risk modifier. Patients wanting to learn more about Lp(a) are likely to use online patient educational materials (OPEMs). However, the readability of OPEMs may exceed the health literacy of the public. OBJECTIVE: This study aims to assess the readability of OPEMs related to Lp(a). We hypothesized that the readability of these online materials would exceed the sixth grade level recommended by the American Medical Association. METHODS: Using an online search engine, we queried the top 20 search results from 10 commonly used Lp(a)-related search terms to identify a total of 200 websites. We excluded duplicate websites, advertised results, research journal articles, or non-patient-directed materials, such as those intended only for health professionals or researchers. Grade level readability was calculated using 5 standard readability metrics (automated readability index, SMOG index, Coleman-Liau index, Gunning Fog score, Flesch-Kincaid score) to produce robust point (mean) and interval (CI) estimates of readability. Generalized estimating equations were used to model grade level readability by each search term, with the 5 readability scores nested within each OPEM. RESULTS: A total of 27 unique websites were identified for analysis. The average readability score for the aggregated results was a 12.2 (95% CI 10.9798-13.3978) grade level. OPEMs were grouped into 6 categories by primary source: industry, lay press, research foundation and nonprofit organizations, university or government, clinic, and other. The most readable category was OPEMs published by universities or government agencies (9.0, 95% CI 6.8-11.3). The least readable OPEMs on average were the ones published by the lay press (13.0, 95% CI 11.2-14.8). All categories exceeded the sixth grade reading level recommended by the American Medical Association. CONCLUSIONS: Lack of access to readable OPEMs may disproportionately affect patients with low health literacy. Ensuring that online content is understandable by broad audiences is a necessary component of increasing the impact of novel therapeutics and recommendations regarding Lp(a).
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Comprensión , Alfabetización en Salud , Humanos , Internet , Lipoproteína(a) , Educación del Paciente como Asunto , Motor de Búsqueda , Estados UnidosRESUMEN
We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P < .001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure.
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Canagliflozina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Antagonistas Adrenérgicos beta/uso terapéutico , Factores de Edad , Anciano , Canagliflozina/efectos adversos , Enfermedades Cardiovasculares/prevención & control , Diuréticos/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Placebos/uso terapéutico , Factores Sexuales , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversosRESUMEN
PURPOSE OF REVIEW: The cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) have increased the focus of type 2 diabetes mellitus (T2DM) care on comprehensive cardiovascular risk reduction. Herein, we review the results of the cardiovascular outcomes trials of SGLT2i and GLP-1 RA, discuss the concepts of relative vs. absolute risk reduction in the context of these trials, and highlight the importance of individualized risk assessment when applying trial results to clinical practice. RECENT FINDINGS: To enable personalized treatment approaches, multiple clinical risk scores have been developed to assess risk of atherosclerotic cardiovascular disease (ASCVD) outcomes and hospitalization for heart failure (HHF) in patients with T2DM. In addition, circulating biomarkers of myocardial injury (cardiac troponin) and hemodynamic stress (natriuretic peptides) have been shown to further refine risk prediction of these clinically important cardiovascular complications. When making decisions about whether to initiate SGLT2i and GLP-1 RA, clinicians should consider the anticipated relative and absolute treatment benefits from these antihyperglycemic therapies. Clinicians can use available clinical and biomarker-based risk tools when counseling patients about their individual cardiovascular risk profiles and when estimating absolute treatment benefits from SGLT2i and GLP-1 RA.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón , Humanos , Hipoglucemiantes/uso terapéutico , Medición de Riesgo , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoAsunto(s)
Aspirina , Enfermedades Cardiovasculares , Humanos , Aspirina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Estados Unidos/epidemiología , Adulto , Masculino , Femenino , Persona de Mediana Edad , Anciano , Inhibidores de Agregación Plaquetaria/uso terapéutico , PrevalenciaRESUMEN
PURPOSE OF REVIEW: Results from cardiovascular (CV) outcome trials have revealed important insights into the CV safety and efficacy of glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). RECENT FINDINGS: Among patients with T2DM, DPP-4i have no significant effect on risk of major adverse CV events (MACE: CV death, myocardial infarction, or stroke) with mixed results regarding risk for heart failure (HF). While sitagliptin and linagliptin have neutral effects on HF risk, saxagliptin significantly increases the risk of HF. The CV safety of the GLP-1RA class of medications has been clearly demonstrated, and select agents, such as liraglutide, semaglutide, albiglutide, and dulaglutide, reduce the risk of MACE in patients with T2DM and established CV disease. CV outcome trials have demonstrated CV safety but not incremental efficacy for DPP-4i in most cases. Select GLP-1RA have proven efficacy for MACE and should be considered by cardiologists for CV risk mitigation in the care of patients with T2DM and established CV disease.
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Cardiólogos , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas , Receptor del Péptido 1 Similar al Glucagón , Humanos , Hipoglucemiantes/efectos adversosRESUMEN
This study examines the appropriateness of artificial intelligence model responses to fundamental cardiovascular disease prevention questions.
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Inteligencia Artificial , Enfermedades Cardiovasculares , Información de Salud al Consumidor , Medios de Comunicación Sociales , Humanos , Enfermedades Cardiovasculares/prevención & control , Atención a la Salud/métodos , Simulación por Computador , Información de Salud al Consumidor/métodosAsunto(s)
Enfermedades Cardiovasculares/etnología , Colesterol/sangre , Fármacos Cardiovasculares/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Guías como Asunto , Humanos , Grupos Raciales , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta de Reducción del Riesgo , Estados UnidosAsunto(s)
Médicos , Ausencia por Enfermedad , Cardiólogos , Humanos , Masculino , Médicos/psicologíaRESUMEN
Cardiovascular disease is the leading cause of death among adults in the USA. Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) are known risk factors for cardiovascular disease. Despite the development of numerous effective anti-glycemic therapies, we have been unable to completely mitigate cardiovascular risk with glucose lowering alone, and prevention of cardiovascular disease in patients with diabetes is primarily achieved with the use of medications that address other risk factors such as anti-hypertensives or statins. Glucagon-like peptide-1 (GLP-1) is a key hormone in the pathophysiology of diabetes. GLP-1 agonists have been recently approved for the treatment of T2DM as well as for chronic weight management. In this review, we aim to explore the effects of GLP-1 agonists on cardiovascular health with a focus on cardiometabolic variables and cardiac function.
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Enfermedades Cardiovasculares/prevención & control , Péptido 1 Similar al Glucagón/agonistas , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/cirugía , Endotelio/efectos de los fármacos , Humanos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Atherosclerotic plaque results from a complex interplay between lipid deposition, inflammatory changes, cell migration and arterial wall injury. Over the past two decades, clinical trials utilizing invasive arterial imaging modalities, such as intravascular ultrasonography, have shown that reducing levels of atherogenic lipoproteins, mainly serum LDL-cholesterol (LDL-C), to very low levels can safely reduce overall atherosclerotic plaque burden and favourably modify plaque composition. Classically, this outcome has been achieved with intensive statin therapy. Since 2016, newer and potent lipid-lowering strategies, such as proprotein convertase subtilisin-kexin type 9 inhibition, have shown incremental effects on plaque regression and risk of clinical events. Despite maximal reduction in plasma LDL-C levels, considerable residual cardiovascular risk remains in some patients. Therefore, there is a need to study therapeutic approaches that address residual risk beyond LDL-C reduction to promote plaque stabilization or regression. Contemporary imaging modalities, such as coronary computed tomography angiography, enable non-invasive assessment of the overall atherosclerotic plaque burden as well as of certain local plaque characteristics. This technology could allow further study of plaque stabilization and regression using novel therapeutic approaches. Non-invasive plaque assessment might also offer the potential to guide personalized management strategies if validated for this purpose.
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Placa Aterosclerótica , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
Objective: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. Methods: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. Results: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients. At 1 year after incident ASCVD, there was suboptimal statin use (any statins <60 %, high-intensity <25 %) and LDL-c control (<30 %) across groups, with lowest proportions in Black patients for statin use (46.7 %, any statin) and LDL-c control (10.7 %, OR 0.89 (0.81-0.97), referent NHW). Disaggregation of Asian and Hispanic groups unmasked within-group heterogeneity. Conclusions: In patients with incident ASCVD, we describe suboptimal and heterogenous 1-year post-ASCVD guideline-directed statin use and 1-year post-ASCVD LDL-c control across disaggregated race and ethnicity groups. Findings may improve understanding of ASCVD treatment disparities and guide implementation.
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BACKGROUND: There are established sex-specific differences in heart failure with reduced ejection fraction (HFrEF) outcomes. Randomized clinical trials (RCTs) based on cardiovascular outcome benefits, typically either reduced cardiovascular mortality or hospitalization for heart failure (HHF), influence current guidelines for therapy. OBJECTIVES: The authors evaluate the representation of women in HFrEF RCTs that observed reduced all-cause or cardiovascular mortality or HHF. METHODS: We queried Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, and PubMed for HFrEF RCTs that reported a statistically significant benefit of intervention resulting in improved mortality or HHF published from 1980 to 2021. We estimated representation using the participation-to-prevalence ratio (PPR). A PPR of 0.8 to 1.2 was considered representative. RESULTS: The final analysis included 33 RCTs. Women represented only 23.2% of all enrolled participants (n = 24,366/104,972), ranging from 11.4% to 40.1% per trial. Overall PPR was 0.58, with per-trial PPR estimates ranging from 0.29 to 1.00. Only 5 trials (15.2%) had a PPR of women representative of the disease population. Representation did not change significantly over time. The proportion of women in North American trials was significantly greater than trials conducted in Europe (P = 0.03). The proportion of women was greater in industry trials compared to government-funded trials (P = 0.05). CONCLUSIONS: Women are underrepresented in HFrEF RCTs that have demonstrated mortality or HHF benefits and influence current guidelines. Representation is key to further delineation of sex-specific differences in major trial results. Sustained efforts are warranted to ensure equitable and appropriate inclusion of women in HFrEF trials.
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BACKGROUND: The prevalence of obesity has been increasing worldwide, with substantial implications for public health. Obesity is independently associated with cardiovascular morbidity and mortality and is estimated to cost the health system over $200 billion dollars annually. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a practice-changing therapy for weight loss and cardiovascular risk reduction independent of diabetes. METHODS: We used large language models to augment our previously reported artificial intelligence-enabled topic modeling pipeline to analyze over 390,000 unique GLP-1 RA-related Reddit discussions. RESULTS: We find high interest around GLP-1 RAs, with a total of 168 topics and 33 groups focused on the GLP-1 RA experience with weight loss, comparison of side effects between differing GLP-1 RAs and alternate therapies, issues with GLP-1 RA access and supply, and the positive psychological benefits of GLP-1 RAs and associated weight loss. Notably, public sentiment in these discussions was mostly neutral-to-positive. CONCLUSIONS: These findings have important implications for monitoring new side effects not captured in randomized control trials and understanding the public health challenge of drug shortages.
Obesity is a global public health burden that increases heart disease risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of medications originally developed for diabetes but are now used to improve lifespans in those with heart disease and increase weight loss. To better understand how the public views this type of drug, over 390,000 discussions from the social media platform Reddit were analyzed using computer software. Topics of discussion included experiences with weight loss, side effects of different GLP-1 RAs, and concerns about drug access and supply. The results showed a mainly neutral-to-positive view of these medications. The findings may help identify new side effects not previously seen in clinical trials and highlight future directions for research and public health efforts.
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Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Objectives: The authors assessed differences in Lp(a) testing and levels by disaggregated race, ethnicity, and ASCVD risk. Methods: This was a retrospective cohort study of patients from a large California health care system from 2010 to 2021. Eligible individuals were ≥18 years old, with ≥2 primary care visits, and complete race and ethnicity data who underwent Lp(a) testing. Race and ethnicity were self-reported and categorized as follows: non-Hispanic (NH) White, NH-Black, Hispanic (Mexican, Puerto Rican, other), NH-Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, other). Logistic regression models tested associations between elevated Lp(a) (≥50 mg/dL) and race, ethnicity, and ASCVD risk. Results: 13,689 (0.9%) individuals underwent Lp(a) testing with a mean age of 54.6 ± 13.8 years, 49% female, 28.8% NH Asian. Over one-third of those tested had Lp(a) levels ≥50 mg/dL, ranging from 30.7% of Mexican patients to 62.6% of NH-Black patients. The ASCVD risk of those tested varied by race: 73.6% of Asian Indian individuals had <5% 10-year risk, whereas 27.2% of NH-Black had established ASCVD. Lp(a) prevalence ≥50 mg/dL increased across the ASCVD risk spectrum. After adjustment, Hispanic (OR: 0.76 [95% CI: 0.66-0.88]) and Asian (OR: 0.88 [95% CI: 0.81-0.96]) had lower odds of Lp(a) ≥50 mg/dL, whereas Black individuals had higher odds (OR: 2.46 [95% CI: 1.97-3.07]). Conclusions: Lp(a) testing is performed infrequently. Of those tested, Lp(a) levels were frequently elevated and differed significantly across disaggregated race and ethnicity groups. The prevalence of elevated Lp(a) increased with increasing ASCVD risk, with significant variation by race and ethnicity.
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INTRODUCTION: The COVID-19 pandemic disrupted clinical research. CLEAR Outcomes investigated the effect of bempedoic acid (BA) versus placebo in 13 970 patients with statin intolerance and high cardiovascular (CV) risk. BA reduced the risk of the primary endpoint (composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) by 13%. CLEAR Outcomes began before and continued for 2.7 years after the start of the pandemic. METHODS: The impact of the COVID-19 pandemic on patient disposition, adverse events, and major adverse CV events (MACE) in CLEAR Outcomes was assessed. RESULTS: Rates of severe infection, hospitalization, or first MACE associated with a positive COVID-19 test were low and balanced between treatment groups. Rates of all-cause death, non-CV death, and undetermined death increased in the pandemic period compared with the pre-pandemic period, while rates of CV death with a known etiology remained stable. A sensitivity analysis excluding undetermined deaths occurring after the onset of the pandemic from the CV death designation yielded hazard ratios of 0.84 (95% CI, 0.76-0.93) for the primary endpoint and 0.94 (95% CI, 0.76-1.16) for the secondary endpoint of CV death, compared with 0.87 (95% CI, 0.79-0.96) and 1.04 (95% CI, 0.88-1.24), respectively, in the original analysis. CONCLUSION: The CLEAR Outcomes trial continued uninterrupted throughout the COVID-19 pandemic. Certain trial endpoints may have been impacted by the pandemic. Specifically, the classification of undetermined deaths as CV deaths may have attenuated the effect of BA on key efficacy endpoints.