Reduction In Cardiovascular Mortality Research Articles

Post-COVID changes and disparities in cardiovascular mortality rates in the United States

IntroductionThe COVID-19 pandemic disrupted healthcare delivery and increased cardiovascular morbidity and mortality. This study assesses whether cardiovascular mortality rates in the US have recovered post-pandemic and examines the equity of this recovery across different populations. MethodsWe analyzed data from the CDC WONDER database, covering US residents’ mortality from 2018–2023. We focused on cardiovascular diseases, categorized by ischemic heart disease (IHD), heart failure (HF), hypertensive diseases (HTN), and cerebrovascular disease. Age-adjusted mortality rates were calculated for three periods: pre-COVID (2018–2019), during COVID (2020–2021), and post-COVID (2022–2023), stratified by demographic and geographic variables. ResultsCardiovascular age-adjusted mortality rates increased by 5.9% during the pandemic but decreased by 3.4% post-pandemic, resulting in a net increase of 2.4% compared to pre-COVID levels. When compared to pre COVID age-adjusted mortality rates, post COVID IHD mortality age-adjusted mortality rates decreased by 5.0%, while cerebrovascular and HTN age-adjusted mortality rates increased by 5.9% and 28.5%, respectively. Men and younger populations showed higher increases in cardiovascular Age-adjusted mortality rates. Geographic disparities were notable, with significant reductions in cardiovascular mortality in the Northeast and increases in states like Arizona and Oregon. ConclusionThe COVID-19 pandemic led to a surge in cardiovascular mortality, with partial recovery post-pandemic. Significant differences in mortality changes highlight the need for targeted healthcare interventions to address inequities across demographic and geographic groups.

The impact of metformin on mortality in patients with type 2 diabetes mellitus: a prospective cohort study.

Metformin, a widely used antihyperglycemic drug, has shown efficacy in treating type 2 diabetes mellitus (T2DM) and is associated with potential benefits beyond glycemic control. This study investigates the impact of metformin on mortality in T2DM patients using a prospective cohort design utilizing data from the National Health and Nutrition Examination Survey (NHANES). In NHANES 1999-2014, a total of 5813 representative participants aged 20 and above with T2DM were included in the analysis. We utilized Kaplan-Meier survival curves and multivariate Cox regression analysis to investigate the impact of metformin on both all-cause mortality and cause-specific mortality among patients with T2DM. Kaplan-Meier analysis showed a significant reduction in all-cause and cause-specific mortality in metformin users compared to non-users (p < 0.05). Multivariate Cox regression confirmed these findings, indicating that metformin use was associated with a 18% reduction in all-cause mortality (HR = 0.82, 95% CI = 0.73-0.92, p < 0.001) and 25% reduction in cardiovascular mortality (HR = 0.75, 95% CI = 0.60-0.94, p = 0.01). Our results suggest that metformin significantly reduces all-cause and cardiovascular mortality in T2DM patients, highlighting its potential benefits beyond glycemic control. These results contribute to the existing literature by providing robust evidence from a large prospective cohort study. However, further research is needed to validate these findings and elucidate the underlying mechanisms controlling the effects of metformin on mortality outcomes in individuals with T2DM.

Associations between Life's Essential 8 and risks of all-cause and cardiovascular mortality in cancer survivors: A prospective cohort study from NHANES

BackgroundLife's Essential 8 (LE8), an indicator of cardiovascular health (CVH), can predict overall and cardiovascular mortality in the general population. Considering that cancer survivors have a higher risk of cardiovascular disease (CVD), our study aimed to investigate the association between LE8 and the prognosis of cancer survivors. MethodsA total of 2191 cancer survivors were included from the National Health and Nutrition Examination Survey (2005–2018). LE8 scores, derived from eight individual metrics, were categorized into three groups: low (0–49), moderate (50–79), and high (80–100). Cox regression analysis, nonlinear analysis, sensitivity analysis, and subgroup analysis were conducted to explore the association between LE8 scores and mortality risks, adjusting for potential confounders. ResultsDuring a median follow-up of six years, 479 deaths were recorded, including 118 CVD events and 156 cancer events. LE8 scores showed an inverse linear relationship with all-cause and cardiovascular mortality. A 10-point increase in LE8 scores was associated with a 25 % reduction in all-cause mortality (hazard ratio [HR], 0.75; 95 % CI, 0.66–0.85) and a 29 % reduction in cardiovascular mortality (HR, 0.71; 95 % CI, 0.57–0.89). Additionally, moderate CVH was linked to a lower risk of all-cause mortality (HR, 0.55; 95 % CI, 0.37–0.81), while high CVH was associated with an even lower risk (HR, 0.35; 95 % CI, 0.19–0.68). Similarly, moderate CVH demonstrated a decreased risk of cardiovascular mortality (HR, 0.31; 95 % CI, 0.15–0.63), with high CVH showing an even lower risk (HR, 0.23; 95 % CI, 0.09–0.58). However, LE8 scores was not associated with cancer-specific mortality. ConclusionsA higher LE8 score was independently associated with a decreased risk of both all-cause and cardiovascular mortality in cancer survivors, underscoring the significance of optimizing CVH during the survivorship phase of cancer care.

Cost-effectiveness of dapagliflozin as part of various treatment regimens for prevention of cardiovascular death and achieving the target indicator "Reduction of cardiovascular mortality" of the State Program "HealthCare Development" in patients with heart failure with reduced ejection fraction

Aim. To evaluate the dapagliflozin as part of various treatment regimens in patients with heart failure (HF) with reduced ejection fraction (HFrEF) ≤40% receiving medications within federal preferential drug program to achieve the "Reduction of cardiovascular mortality" of the State Program "HealthCare Development". To estimate the costs of reducing the cardiovascular mortality rate by 1 death per 100 thousand of population and achieving 1 percentage point of the target indicator "Reduction of cardiovascular mortality".Material and methods. The target patient population was Russian patients aged over 18 years diagnosed with NYHA class II-IV HFrEF (≤40%), included in the federal preferential drug program. We used model developed based on the DAPA-HF study results. We assessed the costs of drugs, the number of lives saved, the impact of therapy on achievement of the target indicator "Reduction of cardiovascular mortality" and other indicators in the Russian Federation (RF) as a whole and in each subject of the Russian Federation while using dapagliflozin as part of various treatment regimens for HFrEF including angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitor (ARNi), beta blockers, diuretics, mineralocorticoid antagonists, cardiac glycosides.Results. In 2024, the treatment cost of 181351 patients with HFrEF included in the federal preferential drug program with dapagliflozin in combination with standard therapy (ST) will be RUB9265,4 million; in combination with ST without ARNi (ST including ACEi/ARB) — RUB8161,7 million; in combination with ST including ARNi — RUB17837,3 million. The additional number of lives saved when using dapagliflozin in combination with standard therapy was 2394, in combination with standard therapy without ARNi — 2340, in combination with standard therapy, including ARNi — 2913. Costs of therapy per patient per year when using dapagliflozin in combination with standard therapy amounted to RUB51090,90; in combination with standard therapy without ARNI — RUB45004,72; in combination with standard therapy, including ARNI — RUB98358,00. In 2024, the percentage (%) of achievement of the federal target for dapagliflozin in combination with ST is 11,22%, while in combination with standard therapy without ARNi (ST including ACEi/ARB) — 10,96%, in combination with ST including ARNi — 13,65%. Achievement of a 1% target reduction in cardiovascular mortality in 2024 reqiored RUB828,1 million for dapagliflozin in combination with ST, while in combination with ST without ARNI (ST including ACEi/ARB) — RUB748,2 million, in combination with ST including ARNi — RUB1293,3 million.Conclusion. Among the 3 options considered for adding dapagliflozin to ST (ARNi or ACEi/ARB, including ACEi/ARB, including ARNi), ST without ARNI (ST including ACEi/ARB) has the lowest cost required to achieve a 1% target reduction in cardiovascular mortality. At the same time, the standard therapy with ARNI has the highest cost required to achieve a 1% target reduction in cardiovascular mortality, which indicates its least cost-effectiveness.

Modern heart failure treatment is superior to conventional treatment across the left ventricular ejection spectrum: real-life data from the Swedish Heart Failure Registry 2013–2020

ObjectivesThis study is aimed to compare the effectiveness of modern therapy including angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) with conventional heart failure treatment in the real world.BackgroundSince ARNI and SGLT2i were introduced to treat heart failure (HF), its therapeutic regimen has modernized from previous treatment with beta-blocker (BB) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) with mineralocorticoid receptor antagonist (MRA) as added-on in HF with reduced ejection fraction (HFrEF). However, a comparison between conventional and modern treatment strategies with drugs in combination has not been performed.MethodsThis observational study (2013–2020), using the Swedish HF Registry, involved 20,849 HF patients. Patients received either conventional (BB, ACEi/ARB, with/without MRA, n = 20,140) or modern (BB, ACEi/ARB, MRA, SGLT2i or BB, ARNI, MRA with/without SGLT2i, n = 709) treatment at the index visit. The endpoints were all-cause and cardiovascular (CV) mortality.ResultsModern HF therapy was associated with a significant 28% reduction in all-cause mortality (adjusted HR [aHR], 0.72 (0.54–0.96); p = 0.024) and a significant 62% reduction in CV mortality (aHR, 0.38 (0.21–0.68); p = 0.0013) compared to conventional HF treatment. Similar results emerged in a sensitivity analysis using propensity score matching. The interaction analyses did not reveal any trends for EF (< 40% and ≥ 40%), sex, age (< 70 and ≥ 70 years), eGFR (< 60 and ≥ 60 ml/min/1.73 m2), and etiology of HF subgroups.ConclusionIn this nationwide study, modern HF therapy was associated with significantly reduced all-cause and CV mortality, regardless of EF, sex, age, eGFR, and etiology of HF.Graphical abstract

Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials.

Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS. Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity. Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005). PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

Evaluating Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) in Type 2 Diabetes Mellitus: A Systematic Review.

Cardiovascular risks and complications remain elevated in patients with type 2 diabetes even after appropriate control of contributing factors like glycemic control, hypertension, and lipid profile. More efficient methods are needed to address this issue in type 2 diabetics. Newer drugs like glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a cardioprotective effect in addition to glycemic control. This systematic review aims to study the latest literature findings on the cardiovascular effects of GLP-1 RAs in patients with type 2 diabetes. We used PubMed, Google Scholar, Science Direct, and Biomed Central databases for our data collection. Our review adheres to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The outcomes evaluated in the review include major adverse cardiovascular events (MACE), heart failure, stroke, all-cause mortality, and effects on cardiovascular risk factors. After careful inspection and quality check, we included 14 articles in the systematic review. GLP-1 RAs were associated with a significant reduction in cardiovascular mortality, all-cause mortality, nonfatal myocardial infarction (MI), and nonfatal stroke, especially in patients with existing cardiovascular risk factors. However, more evidence is required to determine if these benefits extend to those without such risk factors. Limited data suggest that GLP-1 RAs might have a protective effect on arrhythmias, but this area needs further investigation. Despite their potential, several barriers hinder the widespread use of GLP-1 RAs. In conclusion, GLP-1 RAs significantly reduce cardiovascular mortality, all-cause mortality, nonfatal MI, and stroke, with minor effects on hospitalization due to heart failure. Benefits are greater in patients with cardiovascular risk factors. A comprehensive, multilevel approach to policy development and implementation is necessary to optimize the use of these medications in eligible populations.

Precision medicine for obesity: current evidence and insights for personalization of obesity pharmacotherapy.

Obesity is a chronic and complex disease associated with increased morbidity, mortality, and financial burden. It is expected that by 2030 one of two people in the United States will have obesity. The backbone for obesity management continues to be lifestyle interventions, consisting of calorie deficit diets and increased physical activity levels, however, these interventions are often insufficient to achieve sufficient and maintained weight loss. As a result, multiple patients require additional interventions such as antiobesity medications or bariatric interventions in order to achieve clinically significant weight loss and improvement or resolution of obesity-associated comorbidities. Despite the recent advances in the field of obesity pharmacotherapy that have resulted in never-before-seen weight loss outcomes, comorbidity improvement, and even reduction in cardiovascular mortality, there is still a significant interindividual variability in terms of response to antiobesity medications, with a subset of patients not achieving a clinically significant weight loss. Currently, the trial-and-error paradigm for the selection of antiobesity medications results in increased costs and risks for developing side effects, while also reduces engagement in weight management programs for patients with obesity. The implementation of a precision medicine framework to the selection of antiobesity medications might help reduce heterogeneity and optimize weight loss outcomes by identifying unique subsets of patients, or phenotypes, that have a better response to a specific intervention. The detailed study of energy balance regulation holds promise, as actionable behavioral and physiologic traits could help guide antiobesity medication selection based on previous mechanistic studies. Moreover, the rapid advances in genotyping, multi-omics, and big data analysis might hold the key to discover additional signatures or phenotypes that might respond better to a certain intervention and might permit the widespread adoption of a precision medicine approach for obesity management.

Cardiovascular and All-Cause Mortality Is Affected by Serum Magnesium and Diet Pattern in a Cohort of Dialysis Patients.

Background: Hypomagnesaemia is associated with an increased overall mortality in patients with chronic kidney disease on dialysis (CKD-5D). Mediterranean-style diet (MD), having a high magnesium content, can serve as a form of dietary magnesium supplementation. We examined whether there is a potential link between increased Mediterranean Diet score (MDS) and elevated serum magnesium (sMg) to assess its impact on reducing mortality risk in CKD-5D patients. Methods: In this multi-center prospective observational study, 117 CKD-5D patients (66 on hemodialysis and 51 on peritoneal dialysis) with a mean age of 62 ± 15 years were studied for a median follow-up period of 68 months. After baseline assessment, including measurement of sMg and MDS, all patients were followed up for cardiovascular (CV) and all-cause mortality. Results: Forty deaths occurred, 58% of which were cardiovascular. Patients who were above the median value of sMg (2.2 mg/dL) had a 66% reduction in CV (crude HR, 0.34; 95% CI, 0.11-0.70), and 49% reduction in all-cause (crude HR, 0.51; 95% CI, 0.27-0.96) mortality, even after adjustment for age, malnutrition inflammation score, left ventricular mass index, peripheral vascular disease and diabetes. Similar results were obtained when sMg was analyzed as a continuous variable. sMg was associated directly with MDS (r = 0.230; p = 0.012). Conclusions: Higher sMg levels are strongly and independently associated with reduced CV and all-cause mortality in CKD-5D patients. A strong correlation exists between MDS and sMg. Elevated sMg levels, achieved through MD adherence, can significantly reduce CV mortality, implicating MD as a mediator of the association between sMg and CV mortality.

Impact of physical activity on surrogate markers of cardiovascular disease in the haemodialysis population.

The haemodialysis (HD) population is sedentary, with substantial cardiovascular disease risk. In the general population, small increases in daily step count associate with significant reductions in cardiovascular mortality. This study explores the relationship between daily step count and surrogate markers of cardiovascular disease, including left ventricular ejection fraction (LVEF) and native T1 (a marker of diffuse myocardial fibrosis), within the HD population. This was a post hoc analysis of the association between daily step count and metabolic equivalent of task (MET) and prognostically important cardiac magnetic resonance imaging parameters from the CYCLE-HD study (ISRCTN11299707). Unadjusted linear regression and multiple linear regression adjusted for age, body mass index, dialysis vintage, haemoglobin, hypertension and ultrafiltration volume were performed. Significant relationships were explored with natural cubic spline models with four degrees of freedom (five knots). A total of 107 participants were included [age 56.3±14.1years, 79 (73.8%) males]. The median daily step count was 2558 (interquartile range 1054-4352). There were significant associations between steps and LVEF (β=0.292; P=.009) and steps and native T1 (β=-0.245; P=.035). Further modelling demonstrated most of the increase in LVEF occurred at up to 2000 steps/day and there was an inverse dose-response relationship between steps and native T1, with the most pronounced reduction in native T1 between ≈2500 and 6000 steps/day. The results suggest an association between daily step count and parameters of cardiovascular health in the HD population. These findings support the recommendations for encouraging physical activity but are not the justification. Further research should evaluate whether a simple physical activity intervention improves cardiovascular outcomes in individuals receiving maintenance HD.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 μmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 μmol/L) compared with placebo (95%CI: -1.5 to -0.9; P &lt; 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P &lt; 0.001), NT-proBNP by 25% (95%CI: 18-32; P &lt; 0.001), and QoL scores by 10 points (95%CI: 7-13; P &lt; 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15–50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease.

The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes. We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD-related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short-term finerenone treatment decreased LV end-diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity. We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.

Association between influenza vaccination and one-year all-cause and cardiovascular mortality risk: A self-controlled case series and matched case-control study.

Debates surrounding the efficacy of influenza vaccination for survival benefits persist, and there is a lack of data regarding its duration of protection. A self-controlled case series (SCCS) and a 1:4 matched case-control study were conducted using the National Health Interview Survey (NHIS) and public-use mortality data from 2005 to 2018 in the United States. The SCCS study identified participants who received influenza vaccination within 12 months before the survey and subsequently died within 1 year of postvaccination. The matched case-control study paired participants who died during the influenza season at the time of survey with four survivors. Among 1167 participants in the SCCS study, there was a 46% reduction in all-cause mortality and a 43% reduction in cardiovascular mortality within 29-196 days of postvaccination. The greatest protection was observed during days 29-56 (all-cause mortality: RI: 0.19; 95% CI: 0.12-0.29; cardiovascular mortality: RI: 0.28; 95% CI: 0.14-0.56). Among 626 cases and 2504 controls included in the matched case-control study, influenza vaccination was associated with a reduction in all-cause mortality (OR: 0.74, 95% CI: 0.60-0.92) and cardiovascular mortality (OR: 0.64, 95% CI: 0.44-0.93) during the influenza season. This study highlights the importance of influenza vaccination in reducing the risks of all-cause and cardiovascular mortality, with effects lasting for approximately 6 months.

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.

#206 The effect of dapagliflozin on anemia in patients with CKD

Abstract Background and Aims SGLT2 inhibitors confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). Some studies have analyzed the effects of SGLT2is on hemoglobin levels. Potential mechanisms for rising hemoglobin include hypoxia-induced activation of HIF2α, hepcidin inhibition resulting in iron metabolism modulation, and hemoconcentration. We aimed to evaluate the effect of dapagliflozin on anemia in CKD patients. Method We conducted a prospective study in patients in a single center with eGFR 35-90 ml/min/1.73 m2 who received dapagliflozin 10 mg daily between 6/2022 and 10/2023. The primary outcome was the mean difference in hemoglobin levels 5 months prior and 8 months after initiation of SGLT2i therapy. Results Among 132 patients screened from 6/2022 to 10/2023, 53 were prescribed dapagliflozin 10 mg daily, with a mean eGFR of 53.2 ml/min/1.73 m2. Of those 53 patients, 28 (52.8%) were males and 25 (47.2%) females. No one received any iron supplements or erythropoietin therapy. The mean hemoglobin level 5 months before initiating SGLT2i therapy was 10.5 g/dL, with a mean drop of 0.10 g/dL (95% CI, –0.22 to + 0.06) in 5 months. Eight months following the addition of SGLT2is, patients experienced an increase in hemoglobin levels of 1.03 g/dL (95% CI, 0.84 to 1.14). Overall, we observed a mean hemoglobin difference of 1.13 g/dL (95% CI, 0.84 to 1.41, p &amp;lt; 0.01) before and after initiating SGLT2i therapy. Conclusion The use of dapagliflozin for eight months resulted in a significant elevation in hemoglobin levels in patients with CKD. Further studies can explore of better understanding of the effect and confirm the mechanisms that explain this finding. Elevation of hemoglobin with SGLT2is may be closely linked to the reduction of cardiovascular mortality and heart failure.

TAFAMIDIS FOR TREATMENT OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS: A REAL WORLD EXPERIENCE

Abstract Background A regional network for cardiac amyloidosis (CA) was created in 2019 with the aim of enhancing disease awareness among physicians and favoring appropriate access to innovative diagnostic tools/therapies. The network includes all 14 Cardiology Departments and outpatient clinics from 5 Local Health Units. Therapies for variant (ATTR–v) and wild–type (ATTR–wt) CA have recently become available in Italy. Selected centres with expertise in cardiomyopathies were identified to prescribe new modifying disease drugs. Tafamidis is the first medication approved for the treatment of ATTR–C. The landmark ATTRACT trial showed a reduction in cardiovascular mortality and cardiovascular–related hospitalization in patients treated with tafamidis compared to placebo. From October 2021 tafamidis can be prescribed in Italy according to AIFA criteria (only NYHA I/II patients eligible). The aim of our study is to present the experience of our Network in prescribing tafamidis and to compare the clinical baselibe characteristics of our population and the ATTRACT trial population. Methods Thanks to our network , 189 patients with ATTR–CA were referred to our Center. 58 ATTR patients were treated with tafamidis according to AIFA criteria, while 5 patients with variant–TTR and neuropathy received patisiran iv. The causes of exclusion from tafamidis therapy are shown in figure 1. We prospectively collected all the patientst treated with tafamidis from January 2022 until November 2023. All the data about clinical characteristics, laboratoy findings ECG, echo, bone scintigraphy and concomitant treatment were collected during routin follow–up visits anc compared to those of ATTRACT trial population. Results The main findings of our study are summarized in Table (fig,2) The age of our population was similar to that of the patients enrolled in the ATTR–ACT trial (75,94 ± 11.4 vs. 74,5±7.2, P = 0.21). Of note, our population does not include patients in NYHA class III as the AIFA prescriptive criteria exclude these patients from treatment in Italy. this implies a substantial difference in the distribution of the NYHA class compared to the attract population (p = 0.001). The outcome of our patient was excellent, the drug was well tolerated. Conclusions: Implementing specific clinical network provided excellent results, allowing a precise phenotype/genotype characterization and favoring appropriate access to specific disease–modifying drugs.

Rhythm vs Rate Control Strategy for Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials

BackgroundRhythm control, either with antiarrhythmic drugs or catheter ablation, and rate control strategies are the cornerstones of atrial fibrillation (AF) management. Despite the increasing role of rhythm control over the past few years, it remains inconclusive which strategy is superior in improving clinical outcomes. ObjectivesThis study summarizes the total and time-varying evidence regarding the efficacy of rhythm- vs rate-control strategies in the management of AF. MethodsWe systematically perused the MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science databases for randomized controlled trials from inception to November 2023. We included studies that compared the efficacy of rhythm control (ie, antiarrhythmic drugs classes Ia, Ic, or III, AF catheter ablation, and electrical cardioversion) and rate control (ie, beta-blocker, digitalis, or calcium antagonist) strategies among patients with nonvalvular AF. The primary outcome was cardiovascular (CV) death, whereas secondary outcomes included all-cause death, stroke, hospitalization for heart failure (HF), sinus rhythm at the end of the follow-up, and rhythm control–related adverse events. A cumulative meta-analysis to assess temporal trends and a meta-regression analysis using the percentage of ablation use was performed. ResultsWe identified 18 studies with a total of 17,536 patients (mean age: 68.6 ± 9.7 years, 37.9% females) and a mean follow-up of 28.5 months. Of those, 31.9% had paroxysmal AF. A rhythm control strategy reduced CV death (HR: 0.78; 95% CI: 0.62-0.96), stroke (HR: 0.801; 95% CI: 0.643-0.998), and hospitalization for HF (HR: 0.80; 95% CI: 0.69-0.94) but not all-cause death (HR: 0.86; 95% CI: 0.73-1.02) compared with a rate control strategy. This benefit was driven by contemporary studies, whereas more ablation use within the rhythm control arm was associated with improved outcomes, except stroke. ConclusionsIn patients with AF, a contemporary rhythm control strategy leads to reduced CV mortality, HF events, and stroke compared with a rate control strategy.

Effect of statin add-on therapy on cardiovascular mortality.

Cardiovascular (CV) disease remains a leading cause of mortality despite statin therapy. Statin add-on lipid-lowering therapies have been investigated for CV risk reduction, but their effect on CV mortality has not been reviewed. This review describes CV outcomes trials of add-on therapies to statins, highlighting findings related to the primary composite CV endpoints and the more patient-centric endpoint of CV-related mortality. Add-on ezetimibe met its primary composite CV endpoint vs. statin alone (P = 0.016); however, the individual endpoint of death from CV causes did not differ between groups. Add-on therapy with proprotein convertase subtilisin/kexin type 9 inhibitors achieved the primary composite CV endpoints in the respective CV outcomes trials for alirocumab (P < 0.001) and evolocumab (P < 0.001); however, neither CV outcomes trial found a difference vs. placebo in CV-related mortality. In its CV outcomes trial, icosapent ethyl added to statin therapy significantly reduced the occurrence of the primary composite CV endpoint (P < 0.001) and the individual endpoint of risk of CV-related death (P = 0.03) vs. placebo. A CV outcomes trial of bempedoic acid monotherapy achieved its primary composite CV endpoint vs. placebo (P = 0.004) but not the endpoint of death from CV causes. Statin add-on therapies achieved their CV outcomes trial composite CV endpoints. Proprotein convertase subtilisin/kexin type 9 inhibitors and icosapent ethyl have approved indications for CV risk reduction. Only add-on therapy with icosapent ethyl demonstrated a significant reduction in CV mortality in the overall intent-to-treat population, possibly due to the unique pleiotropic mechanisms of eicosapentaenoic acid independent of lipid-lowering effects.

Initiation and Up-titration of Guideline-directed Medical Therapy for Patients with Heart Failure: Better, Faster, Stronger!

Treatment for heart failure has experienced a major revolution in recent years, and current evidence shows that a combination of four medications (angiotensin receptor-neprilysin inhibitors + β-blockers + mineralocorticoid receptor antagonists + sodium.glucose cotransporter 2 inhibitors) offer the greatest benefit to our patients with significant reductions in cardiovascular mortality, heart failure hospitalisations and all-cause mortality. Unfortunately, despite their proven benefits, the implementation of these therapies is still low. Clinical inertia, and unfounded fear of using these drugs might contribute to this. Recently, evidence from randomised clinical trials has shown that intensive implementation of these therapies in patients with heart failure is safe and effective. In this review, we attempt to tackle some of these misconceptions/fears regarding medical therapy for heart failure and discuss the available evidence showing the best strategies for implementation of these therapies.

Cost-effectiveness of valsartan+sakubitril, dapagliflosin and empagliflosin for prevention of cardiovascular death and reducing cardiovascular mortality within the State Program "Health Development" in patients with heart failure

Aim. To assess cost-effectiveness of valsartan+sakubitril, dapagliflosin and empagliflosin for prevention of cardiovascular death and achieving the target indicator "reduction of cardiovascular mortality" of the State Program "Health Development" in patients with heart failure (HF) of the entire profile of left ventricular ejection fraction in 2023-2024Material and methods. The target population was Russian patients who had acute cardiovascular disease (CVD) and a verified diagnosis of HF and received subsidized drug coverage. Parametric modeling was used to predict cardiovascular mortality. In the corresponding comparative pair, the amount of drug costs required to prevent one cardiovascular death (CVD) was calculated, as well as to achieve a 1% target for reducing cardiovascular mortality in the whole country and separately in each region.Results. To prevent one cardiovascular event, the costs of 1-year val-sartan+sacubitril therapy was RUB11,80 million, dapagliflozin — RUB7,07 million, empagliflozin — RUB13,83 million. The costs required to achieve a 1% target for reducing cardiovascular mortality for valsartan+sacubitril, dapagliflozin and empagliflozin were:• in 2023, RUB6534,0 million, RUB3915,0 million and RUB7654,2 million, respectively;• in 2024, RUB1100,6 million, RUB659,5 million and RUB1289,7 million, respectively.Conclusion. The use of dapagliflozin is characterized by the lowest costs for preventing one cardiovascular event and achieving a 1% target for reducing cardiovascular mortality in 2023-2024.