Reduction In Cardiovascular Events Research Articles

Culprit-Only Revascularization, Single-Setting Complete Revascularization, and Staged Complete Revascularization in Acute Myocardial Infarction: Insights From a Mixed Treatment Comparison Meta-Analysis of Randomized Trials.

Complete revascularization improves cardiovascular outcomes compared with culprit-only revascularization in patients with acute myocardial infarction ([MI]; ST-segment-elevation MI or non-ST-segment-elevation MI) and multivessel coronary artery disease. However, the timing of complete revascularization (single-setting versus staged revascularization) is uncertain. The aim was to compare the outcomes of single-setting complete, staged complete, and culprit vessel-only revascularization in patients with acute MI and multivessel disease. PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized controlled trials that compared 3 revascularization strategies. From 16 randomized controlled trials that randomized 11 876 patients with acute MI and multivessel disease, both single-setting complete and staged complete revascularization reduced primary outcome (cardiovascular mortality/MI; odds ratio [OR], 0.52 [95% CI, 0.41-0.65]; OR, 0.74 [95% CI, 0.62-0.88]), composite of all-cause mortality/MI (OR, 0.52 [95% CI, 0.40-0.67]; OR, 0.78 [95% CI, 0.67-0.91]), major adverse cardiovascular event (OR, 0.42 [95% CI, 0.32-0.56]; OR, 0.62 [95% CI, 0.47-0.82]), MI (OR, 0.39 [95% CI, 0.26-0.57]; OR, 0.73 [95% CI, 0.59-0.90]), and repeat revascularization (OR, 0.30 [95% CI, 0.18-0.47]; OR, 0.46 [95% CI, 0.30-0.71]) compared with culprit-only revascularization. Single-setting complete revascularization reduced cardiovascular mortality/MI (OR, 0.70 [95% CI, 0.55-0.91]), major adverse cardiovascular event (OR, 0.67 [95% CI, 0.50-0.91]), and all-cause mortality/MI driven by a lower risk of MI (OR, 0.53 [95% CI, 0.36-0.77]) compared with staged complete revascularization. Single-setting complete revascularization ranked number 1, followed by staged complete revascularization (number 2) and culprit-only revascularization (number 3) for all outcomes. The results were largely consistent in subgroup analysis comparing ST-segment-elevation MI versus non-ST-segment-elevation MI cohorts. Single-setting complete revascularization may offer the greatest reductions in cardiovascular events in patients with acute MI and multivessel disease. A large-scale randomized trial of single-setting complete versus staged complete revascularization is warranted to evaluate the optimal timing of complete revascularization.

Eicosapentaenoic Acid Improves Endothelial Nitric Oxide Bioavailability Via Changes in Protein Expression During Inflammation.

Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) in relation to on-treatment EPA blood levels. The mechanisms of cardiovascular protection for EPA remain incompletely elucidated but likely involve direct effects on the endothelium. In this study, human ECs were treated with EPA and challenged with the cytokine IL-6 (interleukin-6). Proinflammatory responses in the ECs were confirmed by ELISA capture of sICAM-1 (soluble intercellular adhesion molecule-1) and TNF-α (tumor necrosis factor-α). Global protein expression was determined using liquid chromatography-mass spectrometry tandem mass tag. Release kinetics of NO and peroxynitrite were monitored using porphyrinic nanosensors. IL-6 challenge induced proinflammatory responses from the ECs as evidenced by increased release of sICAM-1 and TNF-α, which correlated with a loss of NO bioavailability. ECs pretreated with EPA modulated expression of 327 proteins by >1-fold (P<0.05), compared with IL-6 alone. EPA augmented expression of proteins involved in NO production, including heme oxygenase-1 and dimethylarginine dimethylaminohydrolase-1, and 34 proteins annotated as associated with neutrophil degranulation. EPA reversed the endothelial NO synthase uncoupling induced by IL-6 as evidenced by an increased [NO]/[peroxynitrite] release ratio (P<0.05). These direct actions of EPA on EC functions during inflammation may contribute to its distinct cardiovascular benefits.

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.

The impact of glucagon-like peptide-1 receptor agonists on proteasome inhibitor-associated cardiotoxicity in patients with multiple myeloma.

e24008 Background: Patients with multiple myeloma undergoing proteasome inhibitor therapies face an elevated risk of cardiotoxicity. Existing evidence in the non-cancer population indicates that glucagon-like peptide-1 receptor agonists (GLP1a) can mitigate the risk of cardiovascular events. We hypothesize that GLP1a may reduce the risk of cardiotoxicity in patients with multiple myeloma undergoing proteasome inhibitor therapies. Methods: We conducted a retrospective, propensity score-matched cohort study by utilizing the TriNetX Analytics Network database, which contains de-identified data spanning over 250 million patients. We included adult patients with multiple myeloma and type 2 diabetes mellitus who received proteasome inhibitor therapy. We matched patients treated with GLP1a and those treated with Dipeptidyl Peptidase 4 (DPP4i) in a 1:1 ratio based on predetermined clinical variables. The primary outcome included major adverse cardiovascular events, defined as a composite of heart failure and heart failure hospitalization, myocardial infarction, and ischemic stroke. Other outcomes included individual cardiovascular events, atrial fibrillation/flutter, and all-cause mortality within 3 years of proteasome inhibitor therapy. Results: We matched 183 patients on GLP1a to patients on DPP4i. The prevalence of hypertension, ischemic heart disease, and use of proteasome inhibitors was similar between cohorts. In a Cox proportional hazard analysis, patients who received GLP1a had an approximately 50% lower risk of major adverse cardiovascular events (HR, 0.53 [95% CI: 0.29-0.96]) compared to those who received DPP4i. Furthermore, GLP1a was associated with a reduction in heart failure and heart failure hospitalization, ischemic stroke, and all-cause mortality. The risks of myocardial infarction and atrial fibrillation/flutter were comparable between the two cohorts. Conclusions: GLP1a were associated with a reduction in major adverse cardiovascular events and mortality among patients with multiple myeloma and diabetes mellitus receiving proteasome inhibitors. [Table: see text]

Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial.

The SELECT trial previously reported a 20% reduction in major adverse cardiovascular events with semaglutide (n = 8,803) versus placebo (n = 8,801) in patients with overweight/obesity and established cardiovascular disease, without diabetes. In the present study, we examined the effect of once-weekly semaglutide 2.4 mg on kidney outcomes in the SELECT trial. The incidence of the pre-specified main composite kidney endpoint (death from kidney disease, initiation of chronic kidney replacement therapy, onset of persistent estimated glomerular filtration rate (eGFR) < 15 ml min-1 1.73 m-2, persistent ≥50% reduction in eGFR or onset of persistent macroalbuminuria) was lower with semaglutide (1.8%) versus placebo (2.2%): hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.63, 0.96; P = 0.02. The treatment benefit at 104 weeks for eGFR was 0.75 ml min-1 1.73 m-2 (95% CI 0.43, 1.06; P < 0.001) overall and 2.19 ml min-1 1.73 m-2 (95% CI 1.00, 3.38; P < 0.001) in patients with baseline eGFR <60 ml min-1 1.73 m-2. These results suggest a benefit of semaglutide on kidney outcomes in individuals with overweight/obesity, without diabetes.ClinicalTrials.gov identifier: NCT03574597 .

#2766 Impact of CKD screening in high-risk populations and guideline-directed therapy on CV event occurrence and costs in Europe: an IMPACT CKD analysis

Abstract Background and Aims Chronic kidney disease (CKD) is a growing health problem in Europe exacerbated by aging and the rise of comorbidities such as diabetes mellitus (DM) and hypertension (HTN). Patients with CKD are often multi-morbid and commonly present with cardiovascular (CV) complications. While CV events including myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF) occur more often in patients with advanced CKD, patients with early-stage CKD are also at increased risk. Patients with CKD also experience an increased risk of CV-related mortality, with many patients dying from CV events prior to kidney failure and renal replacement therapy. CV events also present a significant burden to clinicians and healthcare systems due to the high costs and resource use required to manage and treat them. Despite this multidimensional burden, CKD is currently underdiagnosed in Europe, and CKD screening and treatment are rarely included in public health strategies to improve mortality and health outcomes. This study aims to explore the impact of targeted CKD screening followed by guideline-directed therapy in high-risk populations on CV event occurrence and associated treatment costs across Europe. Method The IMPACT CKD microsimulation model simulates CKD progression, CV events, and comorbidities. CKD status is assigned based on estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio levels (UACR), and CKD progression is predicted by an annual eGFR decline rate. The model was used to compare two scenarios in four country populations (Germany, Netherlands, Spain, United Kingdom [UK]): 1) targeted screening for people with DM and/or HTN followed by optimal compliance to guideline-directed therapy and 2) current practice (no screening, underdiagnosis, low treatment rates). Annual targeted screening assumed both eGFR and UACR testing. Treatment initiation for people diagnosed with CKD was based on Kidney Disease Improving Global Outcomes guidelines with a 90% compliance assumed to approximate maximum clinical benefit. Therapies were assumed to have a multiplicative treatment effect on eGFR decline and CV events. Current practice assumed observed diagnosis rates without screening and observed treatment rates in each country. For both scenarios, the model projected incidence of CV events and associated management costs in year 10 (2032) and cumulatively over the 10 simulated years (2023-2032). Results Results compare the targeted screening followed by guideline-directed treatment scenario to continuation of current practices for Germany, Netherlands, Spain, and UK (Table 1). The timely diagnosis of patients with CKD and effective treatment was associated with a reduction of 46.7-53.3%, 38.9-41.6%, and 42.1-50.5% in the number of MI, stroke, and HHF events, respectively in 2032 across the four countries. These decreases in the number of CV events were accompanied by proportional reductions in costs to treat the events. Additionally, this policy approach resulted in declines in the cumulative 10-year CV event development and associated healthcare costs, with MI having the largest reductions (40.6-47.2%), followed by HHF (37.4-43.0%), and stroke (29.8-36.1%) across the four countries. Conclusion This study illustrated that early identification of high-risk patients with CKD coupled with guideline-directed treatment would yield substantial clinical and economic benefits from reducing CV events across all four European countries. Fewer MI, stroke, and HHF events were projected in patients with CKD in both 2032 and cumulatively from 2023 to 2032 due to delayed disease progression following effective interventions. Driven by the reduced clinical burden, lower healthcare costs for CV event management were also predicted. These findings support the need for the adoption of policies for early diagnosis and treatment of CKD to slow disease progression and mitigate the growing CV disease burden among patients with CKD and for health systems. Future studies should explore the costs associated with targeted CKD screening and the guideline-directed pharmacological therapies for CKD.

#1447 Calcimimetics improve impaired cardiac function and contractility in chronic phosphate loading by activating the CaSR/cAMP signaling cascade

Abstract Background and Aims High phosphate loading stimulate the synthesis of PTH and FGF23 and is associated with increased cardiovascular (CV) mortality. In hemodialysis patients, the administration of calcimimetics led to reductions in PTH and FGF23 and the latter was associated with a lower rate of CV events. We have previously shown that mice with a high dietary phosphate load show elevated PTH and FGF23 levels and develop impaired systolic cardiac function, which could be improved by calcimimetics. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR). Phosphate (Pi) was shown to inactivate the parathyroid CaSR at concentrations &amp;gt;1.4 mM Pi. Whether calcimimetics contribute to CV event reduction indirectly via lowering PTH and FGF23 or directly via activation of the cardiac CaSR is unknown. Method Wild-type mice were fed a high phosphate diet (HPD) ± etelcalcetide (Etl) or a normal phosphate diet (NPD), cardiac function was assessed by echocardiography and Millar catheterization, and cardiac tissue was harvested for histology and RNAseq analyses. In addition, isolated adult mouse cardiomyocytes (AMCM) were stimulated ex vivo with PTH, FGF23 or Pi, contractility and calcium handling were measured with the addition of Etl and activity analyses were performed. Results In addition to the positive effect on HPD-induced systolic cardiac dysfunction, Etl improved impaired LV contractility and reduced fibrosis. RNAseq analyses revealed reduced Ca, PKA and cAMP signaling by HPD. Ex vivo stimulation of AMCM with PTH and FGF23 had no functional effects. In contrast, Pi significantly worsened contractility and Ca handling, which was blunted by Etl co-stimulation. Downstream of cardiac CaSR, Pi reduced the formation of cAMP, which led to PKA-dependent dephosphorylation of PLN and subsequently to lower Serca2a activity, which was ultimately responsible for the reduced contractility. Etl led to improved cardiomyocyte contractility via increased cAMP synthesis and increased PLN phosphorylation and Serca2a activity. Conclusion Our data suggest that Etl ameliorates the Pi-induced pathologic cardiac phenotype associated with high phosphate load via direct activation of CaSR/cAMP signaling cascade, resulting in improvement of cardiomyocyte contractility.

Impact of metabolic bariatric surgery on outcomes and the 10-year risk of major adverse cardiovascular events during a 7-year period: a retrospective cohort study.

Metabolic bariatric surgery offers enduring weight reduction and alleviation of obesity-related comorbidities, including dyslipidemia, diabetes, hypertension, and major adverse cardiovascular events (MACE). Long-term data on one-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy (SADJB-SG) is lacking, necessitating this investigation. In this multicenter prospectively-collected retrospective observational study, 830 adult Taiwanese patients (682 OAGB, 148 SADJB-SG) who underwent surgery from January 1, 2011, to December 31, 2017, were initially identified. Following protocol, 224 patients (177 OAGB, 47 SADJB-SG) with complete follow-up data at various intervals up to three years after surgery were included in the final analysis. The study's primary focus is to evaluate the long-term safety, efficacy, and durability of OAGB and SADJB-SG in promoting weight loss and diabetes remission. Additionally, changes in 10-year and lifetime risks of MACE before and 3-year after surgery are assessed using Taiwan MACE risk prediction model and the China-PAR project model. SADJB-SG patients exhibit higher diabetes prevalence, lower body mass index, and more severe diabetes compared to OAGB. Both groups demonstrate significant improvements in body mass index, diabetes, hypertension, and dyslipidemia three years after surgery, with the most substantial improvements occurring in the second year. The Taiwan MACE risk model reveals a significant reduction in 10-year MACE and stroke risks for both groups. The China-PAR project model indicates a synchronized reduction in atherosclerotic cardiovascular disease 10-year and lifetime risk in both OAGB and SADJB-SG groups. OAGB and SADJB-SG exhibit sustained improvements in weight reduction and obesity-related comorbidities over three years after surgery. Notably, both procedures contribute to a substantial reduction in 10-year MACE, stroke, and atherosclerotic cardiovascular disease risks. These findings underscore the efficacy of OAGB and SADJB-SG in the context of metabolic bariatric surgery.

Dapagliflozin Improves Angiogenesis after Hindlimb Ischemia through the PI3K-Akt-eNOS Pathway.

Recently, the vascular protective effect of anti-diabetic agents has been receiving much attention. Sodium glucose cotransporter 2 (SGLT2) inhibitors had demonstrated reductions in cardiovascular (CV) events. However, the therapeutic effect of dapagliflozin on angiogenesis in peripheral arterial disease was unclear. This study aimed to explore the effect and mechanism of dapagliflozin on angiogenesis after hindlimb ischemia. We first evaluated the effect of dapagliflozin on post-ischemic angiogenesis in the hindlimbs of rats. Laser doppler imaging was used to detect the hindlimb blood perfusion. In addition, we used immunohistochemistry to detect the density of new capillaries after ischemia. The relevant signaling pathways of dapagliflozin affecting post-ischemic angiogenesis were screened through phosphoproteomic detection, and then the mechanism of dapagliflozin affecting post-ischemic angiogenesis was verified at the level of human umbilical vein endothelial cells (HUVECs). After subjection to excision of the left femoral artery, all rats were randomly distributed into two groups: the dapagliflozin group (left femoral artery resection, receiving intragastric feeding with dapagliflozin (1 mg/kg/d), for 21 consecutive days) and the model group, that is, the positive control group (left femoral artery resection, receiving intragastric feeding with citric acid-sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days). In addition, the control group, that is the negative control group (without left femoral artery resection, receiving intragastric feeding with citric acid-sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days) was added. At day 21 post-surgery, the dapagliflozin-treatment group had the greatest blood perfusion, accompanied by elevated capillary density. The results showed that dapagliflozin could promote angiogenesis after hindlimb ischemia. Then, the ischemic hindlimb adductor-muscle tissue samples from three rats of model group and dapagliflozin group were taken for phosphoproteomic testing. The results showed that the PI3K-Akt-eNOS signaling pathway was closely related to the effect of dapagliflozin on post-ischemic angiogenesis. Our study intended to verify this mechanism from the perspective of endothelial cells. In vitro, dapagliflozin enhanced the tube formation, migration, and proliferation of HUVECs under ischemic and hypoxic conditions. Additionally, the dapagliflozin administration upregulated the expression of angiogenic factors phosphorylated Akt (p-Akt) and phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor A (VEGFA), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. dapagliflozin could promote angiogenesis after ischemia. This effect might be achieved by promoting the activation of the PI3K-Akt-eNOS signaling pathway. This study provided a new perspective, new ideas, and a theoretical basis for the treatment of peripheral arterial disease.

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m-2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597 .

Routine Functional Testing or Standard Care in High-Risk Patients after Percutaneous Coronary Intervention.

This review aimed to collate the available evidence on outcomes following routine functional stress testing vs standard of care (i.e. symptom-guided stress testing) in high-risk patients following percutaneous coronary intervention (PCI). The most recent pragmatic POST-PCI trial provided randomized evidence showing that routine functional stress testing post-PCI did not lead to a reduction in 2-year ischemic cardiovascular events or all-cause mortality, as compared to a symptom-guided standard-of-care approach. This was also true for sub-analyses including multivessel or left main disease, diabetics, as well as following imaging or physiology guided PCI. In the absence of a change in their clinical or functional status suggestive of stent failure, post-PCI routine periodic stress testing in stable patients on guideline-directed medical therapy is currently not recommended by American clinical practice guidelines. While evidence on the cost-effectiveness of routine stress testing strategy is scarce, physician, payer, and policy-level interventions to reduce inappropriate use of routine functional testing need to be addressed.

The effects of Mediterranean Diet on Cardiovascular diseases: a systematic review

Background: Diet and lifestyle-related factors may be responsible for the different geographical distribution of cardiovascular disease incidence. The aim of our study is to conduct a systematic review of the effect of Mediterranean Diet on cardiovascular diseases (CVD), in terms of prevention of both cardiovascular mortality and cardiovascular events. Methods: We undertook a scientific literature search using MEDLINE, Embase and the Cochrane database for systematic reviews. We selected studies that evaluate the association between mortality and morbidity due to CVD and Mediterranean diet considered as primary or secondary prevention intervention, and found 16 articles concerning 13 studies (2 case-control, 3 cohort studies and 8 randomised clinical trials). Results: The analyzed studies indicate a reduction of adverse cardiovascular events by about 30% and 40%, in terms of primary and the secondary prevention, respectively. Concerning the reduction of mortality, a larger corpus of data is available, demonstrating that the Mediterranean diet significantly reduces mortality by 50% or 70% in terms of secondary prevention, and by about 30% for primary prevention. Conclusions: The Mediterranean diet has positive effects over the CVD both in primary and secondary prevention settings. The estimate of the effect is different in different settings and such variability is attributable to the heterogeneity of the enrolled population, which is obviously lower in the general population compared to those who have already had an adverse cardiovascular event.

Balancing innovation and affordability in anti-obesity medications: the role of an alternative weight-maintenance program.

Despite remarkable clinical advances in highly effective anti-obesity medications, their high price and potential budget impact pose a major challenge in balancing equitable access and affordability. While most attention has been focused on the amount of weight loss achieved, less consideration has been paid to interventions to sustain weight loss after an individual stops losing weight. Using a policy simulation model, we quantified the impact of a weight-maintenance program following the weight-loss plateau from the initial full-dose glucagon-like peptide 1 (GLP-1) receptor agonists or incretin mimetic use. We measured long-term health care savings and the loss of some health benefits (eg, maintenance of weight loss, improvements in cardiometabolic risk factors, and reductions in diabetes and cardiovascular events). Our model suggested that, compared with continuous long-term full-dose GLP-1 receptor agonists or incretin mimetic drugs, the alternative weight-maintenance program would generate slightly fewer clinical benefits while generating substantial savings in lifetime health care spending. Using less expensive and potentially less effective alternative weight-maintenance programs may provide additional headroom to expand access to anti-obesity medications during the active weight-loss phase without increasing total health care spending.

Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease-A Narrative Clinical Review.

Diabetic atherosclerosis is a complex process that is characterized by diffuse and unstable lesions increasing 2-4-fold the risk of adverse cardiovascular (CV) events. Diabetic dyslipidemia has a predominant role in coronary artery disease (CAD) and has been the target of classical and emerging pharmaceutical agents with established or promising CV benefits. The aim of the present narrative review was to summarize the effects of classical and novel lipid-lowering pharmaceutical agents on lipid profile and CV outcomes in diabetic patients with established CAD or high risk of CAD. Statins remain the first-line treatment for all diabetic patients since they considerably ameliorate lipid parameters and non-lipid CV risk factors, leading to reduced CV morbidity and mortality. Complementary to statins, ezetimibe exerts lipid-lowering properties with modest but significant reductions in major adverse cardiovascular events (MACEs) and CV mortality. PCSK9 inhibitors considerably reduce LDL-C levels and lower MACEs in diabetic patients. On the other hand, fibrates may confer a very modest decline in MACE incidence, while the CV impact of omega-3 fatty acids is promising but remains questionable. Bempedoic acid and inclisiran have a potential therapeutic role in the management of diabetic dyslipidemia, but this is still not adequately documented. Given the heightened CV risk among individuals with diabetes, more decisive results would be of great importance in the utility of all these drugs.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 μmol/L. Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

Statins As Anti-Hypertensive Therapy: A Systematic Review and Meta-Analysis.

Hypertension is the most prevalent condition in clinical practice. Hypertension, diabetes, and hypercholesterolaemia are major contributing factors to cardiovascular diseases. They commonly coexist in a single patient. Statins have been used as prominent medicines for the reduction of cardiovascular events. Statins have been shown to reduce blood pressure in patients with hypertension and have lipid-lowering properties in recent articles. Statins reduce blood pressure because of their impact on endothelial function, their interactions with the renin-angiotensin system, and their influence on major artery compliance. This meta-analysis aimed to ascertain the effectiveness and efficacy of statins for managing hypertension in patients with hypertension. Systematic searches were conducted on PubMed, Science Direct, Embase, Cochrane Library, and Google Scholar. Randomized controlled trials, systematic trials, and cohort studies were retrieved using keywords on statins and their use in patients with hypertension. Exclusion criteria included studies that were not in the English language, studies that did not include patients on statins with hypertension, studies that did not provide enough information, technical reports, opinions, or editorials, and studies involving patients < 18 years old. The inclusion criteria were randomized controlled trials, meta-analyses, adult patients aged > 18 years old, and studies that were freely available or through institutional login. This meta-analysis scrutinized 9361 randomized controlled trials, clinical trials, meta-analyses, and systematic reviews, of which 32 articles including 25 randomized controlled trials and seven meta-analyses were included in the final analysis. This meta-analysis of the role of statins in hypertensive patients aimed to determine the outcome of hypertension control along with antihypertensive medication. Our study showed that statins are useful in reducing both systolic and diastolic blood pressure. We used a heterogeneous model for analysis due to variations in the study characteristics. The I2 value was 0.33 (0.76, 0.10) for systolic blood pressure and 0/88 (0.86, 0.90) for diastolic blood pressure. The I2 value for the seven meta-analyses included in the study was 1.79 (2.88, 0.69).

Colchicine for the Prevention of Cardiovascular Disease: Potential Global Implementation.

Targeting traditional cardiovascular risk factors is effective in reducing recurrent cardiovascular events, yet the presence of residual cardiovascular risk due to underlying systemic inflammation is a largely unaddressed opportunity. This review aims to comprehensively assess the evolving role of colchicine as a therapeutic approach targeting residual inflammatory risk in the context of those with coronary artery disease (CAD). Inflammation plays a significant role in promoting atherosclerosis, and targeting anti-inflammatory pathways has the potential to decrease cardiovascular events. Low-dose colchicine (0.5mg/day orally), when added to guideline-directed medical care for CAD, safely decreases major adverse cardiovascular events (MACE) by 31% in stable atherosclerosis patients and 23% in those after recent myocardial infarctions. Meta-analyses of recent randomized control trials further support both the efficacy and safety of colchicine, particularly when added to other standard cardiovascular therapies, including statin therapy. The European Society of Cardiology and other national guidelines endorse the use of low-dose colchicine in patients across the spectrum of CAD. Recently, colchicine was FDA-approved in the United States as the first anti-inflammatory therapy for the reduction of cardiovascular events. In a period of a rising incidence of CAD across the globe, colchicine represents a unique opportunity to decrease MACE due to its large magnitude of benefits and general affordability. However, challenges with drug interactions must be addressed, especially in those regions where HIV, hepatitis, and tuberculosis are prevalent. Colchicine is safe and effective at reducing cardiovascular events across a broad spectrum of coronary syndromes. The ability to simultaneously target traditional risk factors and mitigate residual inflammatory risk marks a substantial advancement in cardiovascular prevention strategies, heralding a new era in the global battle against CAD.

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

BackgroundThe 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). ObjectiveWe assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. MethodsThis 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. ResultsWomen 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. ConclusionsAlirocumab improves cardiovascular outcomes after ACS irrespective of sex. Reduction of total cardiovascular events was greater at higher baseline lipoprotein(a).

Antithrombotic therapy in acute coronary syndrome

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.