Reproductive factors and risk of cardiovascular outcomes in women with ST-elevation myocardial infarction.

BACKGROUND: There are many sex-specific factors affecting myocardial infarction (MI) outcomes in males and females. This study aimed to evaluate the relationship between reproductive factors and cardiovascular outcomes in women after ST-elevation MI. METHOD: This retrospective cohort study was initiated in 2016-2017 at Chamran Hospital, Isfahan, Iran. One hundred eighty women with a diagnosis of ST-elevation MI were followed up for 3 years, and any occurrence of cardiovascular events (CVs) was recorded. All information regarding reproductive factors was recorded via questionnaire. This information was compared between women with cardiovascular events and women without adverse events using a sample t test, chi-square test, and multiple backward logistic regression analysis. SPSS version 24 was used to conduct all analyses. RESULT: Sixty-four women with a mean age of 65.81 ± 13.14 years experienced CV events, and 116 women with a mean age of 65.51 ± 10.88 years did not experience CV events. A history of ischemic heart disease and diabetes mellitus were more prevalent in women with CV events (P = 0.024 and P = 0.019). After adjusting for ischemic heart disease and diabetes mellitus, oral contraceptive pill (OCP) usage was more prevalent in women with CV events than in women without CV events (60.9% vs. 40.4%, P = 0.008). There was a greater chance of CV events in women with OCP usage (OR = 3.546, P = 0.038) and a lower chance of CV events in women with greater age at menarche (OR = 0.630, P = 0.009) and longer breastfeeding duration (OR = 0.798, P = 0.041) according to multiple backward logistic regression models. CONCLUSION: Based on this study, OCP consumption is a risk factor, while older age at menarche and longer duration of breastfeeding are protective factors for cardiovascular outcomes in women after STEMI.

Glycaemic control is still central in the hierarchy of priorities in type 2 diabetes management.

A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes.

Risk of cardiovascular outcomes with bempedoic acid in high-risk statin intolerant patients: a systematic review and meta analysis.

Aim: Statin intolerance and myopathy is a major issue with prolonged use of statins myopathy. Bempedoic acid can be a good alternative for those intolerant to statins. This systematic review aims to observe incidence of major adverse cardiovascular events (MACE) and other adverse events, in high-risk statin intolerant patients receiving bempedoic acid. Methods: Literature search was conducted via Google Scholar, Science Direct and PubMed, after which screening, selection and data extraction of articles was done. Meta-analysis was performed on RevMan 5.4. Subgroup analysis was also conducted and heterogeneity was evaluated. Risk of bias was performed using ROB2 assessment scale. (CRD42024536827). Results: Only six randomized controlled trials were used in final analysis consisting of 17,844 patients. Treatment with bempedoic acid was associated with a reduced risk of MACE compared with placebo (RR 0.86; 95% CI [0.79, 0.94] p = 0.0005), with myocardial infarction significantly reduced. Incidence of adverse effects was increased with bempedoic acid (RR: 1.02; 95% [1.00, 1.03] p = 0.01) but no significant difference was observed. Incidence of myalgia was reduced in bempedoic group as well. Conclusion: Bempedoic acid is a safe and effective alternative to statins in high-risk patients intolerant to statins, decreasing the risk of MACE.

What is this summary about? Low density lipoprotein (LDL-C) also known as 'bad cholesterol', is the culprit behind many heart diseases. Statins are first-line treatment to reduce LDL-C. Despite being extremely effective, some people are intolerant and experience side effects such as sleep disorders, intestinal diseases and most commonly, effects on muscles ranging from muscle pain to breakdown of muscles leading to kidney damage. Bempedoic acid is a once-a-day medication, increasing LDL-C clearance from blood, reducing the risk of heart attack and diabetes and is effective for patients intolerant to statins. This article provides insights into incidences of major heart-related, and other adverse events in patients receiving bempedoic acid.What were the results? Muscle pain and major heart-related events were reduced (especially heart attack) in patients receiving bempedoic acid as compared with those receiving placebos. Muscle weakness and other adverse events were seen in patients receiving bempedoic acid, but serious adverse events were not significantly different from those receiving placebos.What do the results mean? Bempedoic acid is a safe and effective treatment that can be given to patients who cannot tolerate statins or develop side effects to it, as it reduces the risk of heart-related adverse events.

Blood Pressure Time in Target Range and its Impact on Clinical Outcomes.

PURPOSE OF REVIEW: To examine the concept of time in target range for blood pressure (BP) management, exploring its calculation methods, implications for patient outcomes, and potential use in patient care. RECENT FINDINGS: Recent post-hoc analyses of clinical trials and observational studies highlight the importance of BP time in target range in predicting cardiovascular outcomes. Higher time in target range correlates with reduced risks of major adverse cardiovascular events including heart failure, stroke, myocardial infarction and all-cause mortality. Additionally, longer time in target range decreases the risk of incident atrial fibrillation and risk of developing dementia. BP time in target range is a novel metric offering valuable insights into BP control and its impact on clinical outcomes. Higher time in target range is consistently associated with better cardiovascular outcomes across various patient populations. However, the clinical application of BP time in target range requires further investigation through prospective clinical trials and real-world studies. Integrating wearable devices for continuous BP monitoring could enhance the practical utility of BP time in target range in hypertension management.

Ashwagandha's Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes-A Review.

Withania somnifera, commonly known as Ashwagandha, has been popular for many years. Numerous studies have shown that the extract of this plant, due to its wealth of active substances, can induce anti-inflammatory, neuroprotective, immunomodulatory, hepatoprotective, cardioprotective, anti-diabetic, adaptogenic, anti-arthritic, anti-stress, and antimicrobial effects. This review examines the impact of Ashwagandha extract on the vascular endothelium, inflammation, lipid metabolism, and cardiovascular outcomes. Studies have shown that Ashwagandha extracts exhibit an anti-angiogenic effect by inhibiting vascular endothelial growth factor (VEGF)-induced capillary sprouting and formation by lowering the mean density of microvessels. Furthermore, the results of numerous studies highlight the anti-inflammatory role of Ashwagandha extract, as the action of this plant causes a decrease in the expression of pro-inflammatory cytokines. Interestingly, withanolides, present in Ashwagandha root, have shown the ability to inhibit the differentiation of preadipocytes into adipocytes. Research results have also proved that W. somnifera demonstrates cardioprotective effects due to its antioxidant properties and reduces ischemia/reperfusion-induced apoptosis. It seems that this plant can be successfully used as a potential treatment for several conditions, mainly those with increased inflammation. More research is needed to elucidate the exact mechanisms by which the substances contained in W. somnifera extracts can act in the human body.

Associations of SGLT-2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Background: Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM) and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Methods: Patients ≥ 18 years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over two years from HT initiation. Results: After propensity score matching, 2,155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (HR 0.689, 95% CI 0.582-0.816; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations and all-cause mortality. Conclusions: Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: a report from the ODYSSEY OUTCOMES study.

BACKGROUND: The ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS). OBJECTIVE: We assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. METHODS: This prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment. RESULTS: Women were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes. CONCLUSIONS: Alirocumab improves cardiovascular outcomes after ACS irrespective of sex. Reduction of total cardiovascular events was greater at higher baseline lipoprotein(a).

Potential perioperative cardiovascular outcomes in cannabis/cannabinoid users. A call for caution.

Background: Cannabis is one of the most widely used psychoactive substances. Its components act through several pathways, producing a myriad of side effects, of which cardiovascular events are the most life-threatening. However, only a limited number of studies address cannabis's perioperative impact on patients during noncardiac surgery. Methods: Studies were identified by searching the PubMed, Medline, EMBASE, and Google Scholar databases using relevant keyword combinations pertinent to the topic. Results: Current evidence shows that cannabis use may cause several cardiovascular events, including abnormalities in cardiac rhythm, myocardial infarction, heart failure, and cerebrovascular events. Additionally, cannabis interacts with anticoagulants and antiplatelet agents, decreasing their efficacy. Finally, the interplay of cannabis with inhalational and intravenous anesthetic agents may lead to adverse perioperative cardiovascular outcomes. Conclusions: The use of cannabis can trigger cardiovascular events that may depend on factors such as the duration of consumption, the route of administration of the drug, and the dose consumed, which places these patients at risk of drug-drug interactions with anesthetic agents. However, large prospective randomized clinical trials are needed to further elucidate gaps in the body of knowledge regarding which patient population has a greater risk of perioperative complications after cannabis consumption.

Effect of Elevated Neutrophil-to-Lymphocyte Ratio on Adverse Outcomes in Patients With Myocardial Infarction: A Systematic Review and Meta-Analysis.

Myocardial infarction (MI), a leading cause of morbidity and mortality globally, is characterized by an underlying inflammatory process driven by atherosclerosis. The neutrophil-to-lymphocyte ratio (NLR), a readily available and cost-effective marker of systemic inflammation, has emerged as a potential predictor of adverse outcomes in patients with MI. This meta-analysis aimed to evaluate the association between elevated NLR and the risk of major adverse cardiovascular events (MACE) and all-cause mortality in patients with MI. A comprehensive literature search was conducted across multiple databases, including Embase, Web of Science, PubMed, and OVID Medicine, to identify relevant studies published from January 1, 2011, onward. Studies reporting the effect of NLR values on MACE and mortality in adult patients with MI, including both ST-elevation (STEMI) and non-ST-elevation (NSTEMI) subtypes, were included. Data extraction and quality assessment were performed independently by multiple authors. The meta-analysis included 37 studies, comprising a total of 18 studies evaluating the risk of MACE and 30 studies assessing all-cause mortality. The pooled analysis revealed a significantly increased risk of MACE (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.53-2.28, P < 0.01) and all-cause mortality (OR 2.29, 95% CI 1.94-2.70, P < 0.01) in patients with elevated NLR compared to those without elevated NLR. Subgroup analyses stratified by follow-up duration and study design further supported the consistent association between elevated NLR and adverse outcomes. In conclusion, this meta-analysis demonstrates a significant association between elevated NLR and an increased risk of MACE and all-cause mortality in patients with MI. These findings highlight the potential clinical utility of NLR as a prognostic marker and underscore the importance of further research to validate its predictive value and establish optimal cutoff values for risk stratification in this patient population.

A Systematic Review and Meta-Analysis on the Role of Bempedoic Acid in Cardiovascular Outcomes for Patients With Statin Intolerance.

Atherosclerosis, a multifaceted pathogenic process affecting the arteries and aorta, poses a significant threat because of its potential to impede or entirely obstruct blood flow by narrowing blood vessels. This intricate progression involves various factors such as dyslipidemia, immunological responses, inflammation, and endothelial dysfunction. The initial phase manifests as the formation of fatty streaks, considered a pivotal hallmark in the inception of atherosclerotic plaques, a process that can commence as early as childhood. Over time, this process evolves, characterized by the thickening of the arterial inner layer (intima) and accumulation of lipid-laden macrophages, commonly known as foam cells, along with the buildup of the extracellular matrix. Subsequent stages witness the proliferation and aggregation of smooth muscle cells, culminating in the formation of atheroma plaques. As these lesions progress, apoptosis can occur in the deeper layers, further recruiting macrophages, which may undergo calcification and transform into atherosclerotic plaques. Notably, mechanisms such as arterial remodeling and intraplaque hemorrhage also contribute significantly to the progression of atherosclerotic cardiovascular disease, although these facets fall beyond the scope of this article. This study aimed to systematically review and conduct a meta-analysis of randomized controlled trials investigating the efficacy and safety of bempedoic acid in statin-intolerant patients with hyperlipidemia and to provide conclusions and recommendations accordingly. A systematic search of databases, such as PubMed, Web of Science, and Embase, will be performed. Only randomized trials will be included comparing bempedoic acid with placebo in statin-intolerant patients. This study aimed to provide a comprehensive understanding of the role of bempedoic acid in managing hyperlipidemia in statin-intolerant patients. In primary prevention, for patients unable to tolerate recommended statins, bempedoic acid was associated with a significant reduction in major adverse cardiovascular events (MACE) as the primary endpoint.

Relation between blood pressure time in range and composite cardiovascular outcomes in patients with primary aldosteronism: a retrospective case study.

PURPOSE: To investigate the association between blood pressure (BP) time in range (TIR) and composite cardiovascular outcomes in patients with primary aldosteronism (PA). METHODS: Between January 2019 and December 2021, 47 patients with PA were recruited from the First Affiliated Hospital of Xiamen University. Twenty-four-hour ambulatory BP monitoring (ABPM) and cardiovascular outcomes were assessed in all patients during the first diagnosis of PA. RESULTS: The mean age of the patients was 48.8 ± 11.4 years. Compared to PA without composite cardiovascular outcomes, the nighttime systolic BP TIR [31.2% (6.2%, 81.2%) vs. 11.5% (0.0%, 29.7%), p = 0.02] and defined daily dose (DDDs) of antihypertensive medication [2.0 (1.0, 2.8) vs. 1.0 (1.0, 2.0), p = 0.03] were lower in PA patients with composite cardiovascular outcomes, while higher glucose (5.0 ± 1.0 mmol/L vs. 5.9 ± 1.5 mmol/L) and prevalence of a history of alcohol intake was higher in PA patients with composite cardiovascular outcomes. There were no differences in age, sex, BMI, smoking, duration of hypertension, lipid levels, aldosteronism, clinic BP, 24-hour mean BP, daytime or nighttime BP, percentage of nocturnal SBP or DBP decline, 24-hour BP TIR, daytime BP TIR, or nighttime DBP TIR between the two groups. After adjusting for confounding factors, nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes (adjusted OR = 0.92 [95% CI 0.86, 0.99]) in multiple logistic regression analysis. CONCLUSION: Nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes in patients with PA.

Comparative effectiveness of positron emission tomography and single-photon emission computed tomography myocardial perfusion imaging for predicting risk in patients with cardiometabolic disease.

BACKGROUND: The epidemiology of coronary artery disease (CAD) has shifted, with increasing prevalence of cardiometabolic disease and decreasing findings of obstructive CAD on myocardial perfusion imaging (MPI). Coronary microvascular dysfunction (CMD), defined as impaired myocardial flow reserve (MFR) by positron emission tomography (PET), has emerged as a key mediator of risk. We aimed to assess whether PET MFR provides additive value for risk stratification of cardiometabolic disease patients compared with single-photon emission computed tomography (SPECT) MPI. METHODS: We retrospectively followed patients referred for PET, exercise SPECT, or pharmacologic SPECT MPI with cardiometabolic disease (obesity, diabetes, or chronic kidney disease) and without known CAD. We compared rates and hazards of composite major adverse cardiovascular events (MACEs) (annualized cardiac mortality or acute myocardial infarction) among propensity-matched PET and SPECT patients using Poisson and Cox regression. Normal SPECT was defined as a total perfusion deficit (TPD) of <5%, reflecting the absence of obstructive CAD. Normal PET was defined as a TPD of <5% plus an MFR of ≥2.0. RESULTS: Among 21,544 patients referred from 2006 to 2020, cardiometabolic disease was highly prevalent (PET: 2308 [67%], SPECT: 9984 [55%]) and higher among patients referred to PET (P < 0.001). Obstructive CAD findings (TPD > 5%) were uncommon (PET: 21% and SPECT: 11%). Conversely, impaired MFR on PET (<2.0) was common (62%). In a propensity-matched analysis over a median 6.4-year follow-up, normal PET identified low-risk (0.9%/year MACE) patients, and abnormal PET identified high-risk (4.2%/year MACE) patients with cardiometabolic disease; conversely, those with normal pharmacologic SPECT remained moderate-risk (1.6%/year, P < 0.001 compared to normal PET). CONCLUSIONS: Cardiometabolic disease is common among patients referred for MPI and is associated with a heterogenous level of risk. Compared with pharmacologic SPECT, PET with MFR can detect nonobstructive CAD including CMD and can more accurately discriminate low-risk from higher-risk individuals.

Curbing the Obesity Epidemic: Should GLP-1 Receptor Agonists Be the Standard of Care for Obesity?

PURPOSE OF REVIEW: This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity. RECENT FINDINGS: Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity. The SELECT trial demonstrated that semaglutide led to a reduction in major adverse cardiovascular events in patients without diabetes who were either overweight and had preexisting cardiovascular disease or obese. SUMMARY: The treatment of obesity is critical to prevent the progression of cardiovascular-kidney-metabolic syndrome. Incretin-based therapies offer remarkable weight loss and reduce major cardiovascular adverse events.

Reducing racial and ethnic disparities in cardiovascular outcomes among cancer survivors.

PURPOSE OF REVIEW: Analyze current evidence on racial/ethnic disparities in cardiovascular outcomes among cancer survivors, identifying factors and proposing measures to address health inequities. RECENT FINDINGS: Existing literature indicates that the Black population experiences worse cardiovascular outcomes following the diagnosis of both initial primary cancer and second primary cancer, with a notably higher prevalence of cardio-toxic events, particularly among breast cancer survivors. Contributing socioeconomic factors to these disparities include unfavorable social determinants of health, inadequate insurance coverage, and structural racism within the healthcare system. Additionally, proinflammatory epigenetic modification is hypothesized to be a contributing genetic variation factor. Addressing these disparities requires a multiperspective approach, encompassing efforts to address racial disparities and social determinants of health within the healthcare system, refine healthcare policies and access, and integrate historically stigmatized racial groups into clinical research. Racial and ethnic disparities persist in cardiovascular outcomes among cancer survivors, driven by multifactorial causes, predominantly associated with social determinants of health. Addressing these healthcare inequities is imperative, and timely efforts must be implemented to narrow the existing gap effectively.

Comparison of atrial fibrillation prevalence and in-hospital cardiovascular outcomes between patients undergoing allogeneic versus autologous hematopoietic stem cell transplantation: insights from the national inpatient sample.

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant hematologic conditions. However, patients undergoing HSCT are at increased risk of developing serious cardiovascular events. Whether cardiovascular risks differ by the type of transplantation strategy used, allogeneic versus autologous HSCT, is unknown. Leveraging the National Inpatient Sample (2016-2019), we assessed the incidence of early cardiovascular events by HSCT mode (allogeneic vs autologous). The primary outcome was the incidence of atrial fibrillation (AF). The secondary outcome was the occurrence of any major adverse cardiac events (MACE), defined as acute heart failure, myocardial infarction (MI), symptomatic atrial or ventricular arrhythmia or heart block, and cardiovascular death. Outcomes were compared between those undergoing allogeneic versus autologous HSCT. Multivariable regression, adjusting for cardiovascular and cancer-related factors, was used to define the association between pre-HSCT factors and MACE. We further assessed the effect of acute cardiovascular events on in-patient mortality by calculating adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI) and p-values. Overall, 64,705 weighted hospitalizations for HSCT were identified, of which 22,655 (35.0%) were allogeneic HSCT and 42,050 (65.0%) were autologous HSCT. The prevalence of AF was 9.1%, and 12.1% for any arrhythmia. In multivariable regression, allogeneic HSCT was associated with higher adjusted odds of peri-HSCT acute heart failure (aOR 2.64; 1.86-3.76; p < 0.0001), QT prolongation (aOR 1.40; 1.04-1.88; p = 0.025), MI (aOR 2.87; 1.16-7.11; p = 0.023), any major cardiovascular complication (aOR 1.16; 1.03-1.32; p = 0.016), and inpatient mortality (aOR 4.87; 3.60-6.58; p < 0.0001). Following cerebrovascular events, AF was the strongest predictor of mortality. Allogeneic HSCT was associated with higher odds of in-hospital cardiovascular complications among patients undergoing HSCT.

Review of Evolocumab for the Reduction of LDL Cholesterol and Secondary Prevention of Atherosclerotic Cardiovascular Disease.

Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of > 60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of > 90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in > 51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.

Impact of the COVID-19 Pandemic on Conduct and Results of CLEAR Outcomes Trial.

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.

Outcomes of Early Versus Delayed Anemia Treatment in Nondialysis-Dependent CKD.

Introduction: The association of hemoglobin level at treatment initiation with renal and cardiovascular outcomes in patients with anemia in nondialysis-dependent (NDD) chronic kidney disease (CKD) is unclear. Methods: This retrospective cohort study utilized 2 Japanese databases (Medical Data Vision Co. Ltd., Tokyo, Japan [MDV]; and Real World Data Co. Ltd, Kyoto, Japan [RWD]). Patients initiated on long-acting erythropoiesis-stimulating agent (ESA) treatment were divided into early (hemoglobin levels ≥9.0 g/dl) and delayed (<9.0 g/dl) treatment groups. The primary outcome was a renal composite (renal replacement therapy, ≥50% estimated glomerular filtration rate [eGFR] reduction, eGFR <6.0 ml/min per 1.73 m2, and all-cause mortality), and secondary outcomes were a cardiovascular composite (hospitalization by ischemic heart disease, including myocardial infarction, hospitalization by stroke and heart failure, and cardiovascular death) and components of the composite outcomes. Results: After propensity score matching, 1472 (MDV) and 1264 (RWD) patients were evaluated. Delayed treatment was not associated with a risk of the renal composite outcome (MDV: hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 0.99-1.33; RWD: HR: 1.08, 95% CI: 0.92-1.28). However, delayed treatment was associated with higher risks of the cardiovascular composite outcome (MDV: HR: 1.47, 95% CI: 1.16-1.84; RWD: HR: 1.34, 95% CI: 1.09-1.64), heart failure (MDV: HR: 1.50, 95% CI: 1.13-2.00; RWD: HR: 1.53, 95% CI: 1.20-1.96) and all-cause mortality (MDV: HR: 1.83, 95% CI: 1.32-2.54; RWD: HR: 1.64, 95% CI: 1.21-2.22). Conclusion: Although the risk of renal events was not increased following delayed treatment of anemia in patients with NDD-CKD, the risks of cardiovascular events and all-cause mortality were increased, suggesting the importance of early intervention before hemoglobin falls below 9.0 g/dl.