INTRODUCTION: The interplay between lipid metabolism and renal injury in the context of metabolic kidney diseases has garnered growing scientific interest. Nevertheless, the majority of existing studies have primarily co...INTRODUCTION: The interplay between lipid metabolism and renal injury in the context of metabolic kidney diseases has garnered growing scientific interest. Nevertheless, the majority of existing studies have primarily concentrated on the modulation of individual lipid parameters, with relatively limited emphasis on the potential role of PCSK9 as a crucial mediator linking lipid metabolism disturbances to kidney damage. METHODS: A comprehensive literature search was performed across databases such as PubMed and Web of Science, covering the period from 2003 to 2025. Search terms included "PCSK9," "metabolic kidney disease," and "chronic kidney disease", which were used to identify relevant Randomized Controlled Trials (RCTs), systematic reviews, and mechanistic studies. In addition, proteomics data were obtained from the iProX database and integrated into the analysis. RESULTS: PCSK9 exacerbates lipid metabolism dysregulation through LDLR degradation. Its inhibitors improve lipid metabolism and reduce proteinuria, thereby exerting renoprotective effects via downregulation of lipid-related proteins (e.g., Angptl3) and inhibition of TGF-β signaling components. DISCUSSION: PCSK9 as a therapeutic target, extending prior research by demonstrating dual lipidrenal protective effects. However, evidence for rare metabolic kidney diseases and long-term safety data is lacking. CONCLUSION: PCSK9 inhibitors show promise in metabolic kidney diseases, but large-scale trials are needed to clarify their long-term efficacy and optimal application scope.
Over the last few decades, there has been noteworthy long-lasting stagnancy in the field of antiarrhythmic drugs (AAD), with the development of novel AAD notably declining over the years. Although ablation therapy has do...Over the last few decades, there has been noteworthy long-lasting stagnancy in the field of antiarrhythmic drugs (AAD), with the development of novel AAD notably declining over the years. Although ablation therapy has dominated, there remains an unmet need for effective and safe antiarrhythmic therapy in those choosing a conservative approach and those failing the ablation procedure( s). Also, in patients with life-threatening ventricular arrhythmias, in the era of the implantable cardioverter defibrillator dominance, many patients require effective and safe AAD therapy to mitigate the recurrence of arrhythmias and the delivery of painful and unpleasant device shocks. The repurposing and reformulation of current drugs in circulation for novel therapeutic uses may provide new avenues for developing antiarrhythmic treatments that can assist in curtailing cardiac arrhythmia- associated morbidity and mortality, and ameliorate the quality of life for millions of patients. Stressful factors may lead to endothelial dysfunction and a surge in blood pressure, contributing to the emergence of cardiac arrhythmogenic effects, including myocardial fibrosis and remodeling of structural, ion channels, and connexin 43 channels, with consequent dysfunction. Agents influencing this latter protein may have cardioprotective and potentially antiarrhythmic effects. In this review of new antiarrhythmic agents, the advantages of sodium-glucose co-transporter inhibitors, and also those of pirfenidone, ranolazine, sotatercept, mirabegron, nintedanib, and melatonin are discussed. Some of these agents have been approved for other indications and repurposed for use in managing arrhythmias. Finding novel antiarrhythmic therapeutic approaches may be challenging for further research.
INTRODUCTION: The ductus arteriosus is a vital fetal vessel connecting the pulmonary artery to the aorta, facilitating blood flow away from the non-functional fetal lungs. Drug exposure during pregnancy may affect DA phy...INTRODUCTION: The ductus arteriosus is a vital fetal vessel connecting the pulmonary artery to the aorta, facilitating blood flow away from the non-functional fetal lungs. Drug exposure during pregnancy may affect DA physiology, leading to conditions like premature DA closure, DA stenosis, or Patent Ductus Arteriosus (PDA). To identify drugs with maternal exposure that may be linked to alterations in the fetal and neonatal Ductus Arteriosus (DA). This study examines associations between various drugs and alterations in DA using data from the USFDA Adverse Event Reporting System (AERS) through disproportionality analysis. METHODS: Data from March 2004 to June 2024 were extracted from the AERS database, focusing on MedDRA Preferred Terms (PTs) for PDA, DA premature closure, and DA stenosis, combined with "fetal exposure during pregnancy." Following deduplication, 1,878 unique cases (PDA: 1,444; DA stenosis: 213; DA closure: 221) were analyzed. Disproportionality signals were detected using frequentist [Reporting Odds Ratio and Proportional Reporting Ratio (PRR)] and Bayesian (Bayesian Confidence Propagation Neural Network and Multi-Item Gamma Poisson Shrinker) methods to assess associations. Signals were considered when there were at least three cases, a PRR value of ≥ 2, and a Chi-square (χ2) value of ≥ 4 according to Evan's criteria. Amongst the Bayesian methods, signals were considered when the lower limit of the IC's 95% CI (IC025) >0 and the lower limit of the 95% CI of the Empirical Bayes Geometric Mean (EBGM05) exceeded 2. RESULTS: Diclofenac had the highest number of reports for DA stenosis (number of reports: 118; PRR: 163; χ2: 8401.7; IC025: 4.7; and EBGM05: 55.9) and premature closure stenosis (number of reports: 68; PRR: 58.3; χ2: 2612.8; IC025: 4; and EBGM05: 30.6). Drugs linked with DA stenosis included analgesics (e.g., acetaminophen), antiemetics, and anti-inflammatory agents (e.g., ibuprofen). Premature DA closure was associated with analgesics, anti-inflammatory drugs, and psychoanaleptics. For PDA, signals were detected for a broad spectrum of drugs, including analgesics, antibacterials, anesthetics, antiepileptics, and antihypertensives. PDA cases showed a significantly higher rate of mortality compared to other DA conditions. DISCUSSION: These findings highlighted significant associations between maternal drug exposure and DA alterations, reinforcing known risks (such as NSAID-induced DA closure) and suggesting potential signals for SSRIs and antiepileptics. These results align with established pharmacological mechanisms and regulatory warnings, but must be interpreted cautiously given the limitations of spontaneous reporting data. The study underscores the need for targeted fetal monitoring, provider education, and prospective research to validate signals and refine drug safety guidelines in pregnancy. CONCLUSION: This disproportionality analysis identified significant associations between maternal drug exposure and alterations in the fetal and neonatal DA, including premature closure, stenosis, and PDA. The findings highlighted the need for further pharmacovigilance studies to validate these signals, particularly for drugs with strong disproportionality signals but limited mechanistic evidence. Future research should focus on prospective cohort studies and mechanistic investigations to clarify causality and assess clinical implications. Additionally, risk-benefit evaluations of drug use during pregnancy, especially for analgesics, anti-inflammatory agents, and psychoanaleptics, are warranted to guide safer therapeutic decisions.
INTRODUCTION: People on a ketogenic diet may develop an increase in low-density lipoprotein cholesterol (LDL-C), known as the lean mass hyper-responder (LMHR) phenotype. However, this increase does not necessarily corres...INTRODUCTION: People on a ketogenic diet may develop an increase in low-density lipoprotein cholesterol (LDL-C), known as the lean mass hyper-responder (LMHR) phenotype. However, this increase does not necessarily correspond to a heightened cardiovascular (CV) risk, and optimal treatment strategies for high-risk individuals within this group remain uncertain. CASE PRESENTATION: A 61-year-old man with type 1 diabetes developed the LMHR phenotype after adopting a ketogenic diet. An atherosclerotic plaque was discovered in the bulb of his left common carotid artery, reclassifying him into the secondary prevention category of CV disease. After the introduction of rosuvastatin 20 mg daily, his LDL-C subfraction profile changed from a more atherogenic type B phenotype to a less atherogenic type A phenotype without significantly decreasing overall LDL-C levels. This suggests that rosuvastatin provided a beneficial effect, complementing the metabolic improvements associated with the ketogenic diet, including better blood glucose and insulin control, potential prior reductions in small dense LDL-C and triglycerides, and an increase in high-density lipoprotein cholesterol (HDL-C).In this case, no trend toward a lower threshold was observed for the development of diabetic ketoacidosis. CONCLUSION: Assessing LDL-C subfractions before and after the initiation of lipid-lowering therapy is essential in individuals who develop the lean mass hyper-responder (LMHR) phenotype, particularly in the presence of confirmed atherosclerosis. Given the markedly elevated LDL-C levels often observed in this population, it may be difficult to accurately evaluate the burden of atherogenic cholesterol and the extent of its reduction without subfraction analysis. In such cases, statin therapy appears to be a reasonable and potentially beneficial intervention, even among LMHR individuals.
AIMS: The present analysis of the ARCANGELO study aims to investigate the effect of switching to different oral P2Y12 inhibitors when using cangrelor during PCIs in patients with ACS. METHODS: Out of the 995 patients mee...AIMS: The present analysis of the ARCANGELO study aims to investigate the effect of switching to different oral P2Y12 inhibitors when using cangrelor during PCIs in patients with ACS. METHODS: Out of the 995 patients meeting the criteria for this investigation, 138 transitioned to Clopidogrel (CLO), 127 to rasugrel (PRA), and 730 to Ticagrelor (TICA). Compared to the patients on PRA or TICA, users of CLO were older (median (Q1-Q3) 74(64-81) years CLO, 59(54-65) years PRA, 65(56-73) TICA; p<0.0001), had more comorbidities (37.0% CLO, 17.3% PRA, 18.9% TICA, p<0.0001), and had more frequently an NSTEMI diagnosis (68.1% CLO vs 33.1% PRA vs 35.9% TICA, p<0.0001). RESULTS: Five moderate bleeds were recorded without any severe episodes. There were no significant differences in the bleeding rate when switching to the different oral P2Y12 inhibitors (2.2% CLO, 5.3% TICA, 7.9% PRA, p = 0.0705) while different incidences of MACEs (4.3% CLO, 1.1% TICA, 0% PRA, p = 0.0113) and NACEs (4.3% CLO, 1.8% TICA, 0% PRA, p=0.0321) were observed during the 30 days of the study. CONCLUSION: The use of cangrelor and the switch to any oral P2Y12 inhibitor in compliance with the EU SmPC is safe, with a low risk of ischemic events in routine clinical practice.
Drug-eluting angioplasty balloons are a highly effective treatment for neointimal hyperplasia post-balloon angioplasty and in-stent restenosis. Current drug-eluting angioplasty balloons have restenosis rates approximatin...Drug-eluting angioplasty balloons are a highly effective treatment for neointimal hyperplasia post-balloon angioplasty and in-stent restenosis. Current drug-eluting angioplasty balloons have restenosis rates approximating 20%, and both paclitaxel, the current drug coating of choice, and sirolimus, an alternative coating being evaluated in early clinical studies, delay re-endothelialisation, potentially predisposing to thrombosis. There remains a paucity of efficacious alternatives to these coatings. Research into alternative drug-eluting balloon coatings is the source of intense investigation in attempts to improve on efficacy and safety of this highly effective therapeutic intervention. We discuss recent clinical developments with regard to sirolimus drug-coated balloons, demonstrating efficacy in early studies in relation to coronary, peripheral arterial, and renal access applications. However, limited comparator studies with paclitaxel currently exist. In addition, we explore novel drug-eluting angioplasty balloon coatings currently under evaluation in the preclinical space, together with associated molecular mechanisms of action. Further in vivo evaluation of these potential alternative coatings is required, and an algorithm to support the rational evaluation of novel coatings and their subsequent clinical development has been provided.
Al-Jarallah M, Rajan R, Dashti R
… +23 more, Bulbanat B, Ridha M, Sulaiman K, Al-Zakwani I, Alsheikh-Ali AA, Panduranga P, Alhabib KF, Al Suwaidi J, Almahmeed W, Al Faleh H, Elasfar A, Al-Motarreb A, Bazargani N, Asaad N, Amin H, Kobalava Z, Brady PA, Baca GL, Setiya P, Alsaber AR, Tabatabaei GA, Al Balool J, Razzaghi K
BACKGROUND: The prevalence and clinical outcomes of statin therapy in patients with acute heart failure [AHF] stratified by left ventricular ejection fraction [EF] in the Middle East are unknown. METHODS: We analysed 500...BACKGROUND: The prevalence and clinical outcomes of statin therapy in patients with acute heart failure [AHF] stratified by left ventricular ejection fraction [EF] in the Middle East are unknown. METHODS: We analysed 5005 patients admitted to 47 hospitals in seven Middle Eastern countries [Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain] with AHF from February to November 2012 with AHF who were enrolled in Gulf CARE, a multinational registry of patients with heart failure [HF]. AHF patients were stratified into three groups: HF patients with reduced [EF] [HFrEF] [<40%], HF with mildly reduced EF [HFmrEF] [40-49%], and HF patients with preserved EF [HFpEF] [≥50%]. RESULTS: The mean age of the cohort was 59.3±14.9 years, 62.6% [n=3131.0] of the patients were males. A total of 2555 [51%] AHF patients had used statins prior to hospital admission. The mean EF was 36.9±14%. HFrEF was observed in 2683 patients [53%], whereas 961 patients [19.2%] had HFmrEF, and 932 patients [18.6%] had HFpEF. Multivariate logistic regression analysis revealed that prior statin use was significantly associated with reduced in-hospital mortality risk [OR=1.43, 95% CI: 1.10-1.86, p=0.007] and hospitalization rates for heart failure [OR=0.71, 95% CI: 0.60-0.83, p<0.001]. However, when examining rates of survival, there were no significant disparities between the two groups; at 3 months follow-up: aOR, 1.22; 95% Cl: 0.95-1.57; P=0.111; and 12-months follow-up: aOR, 1.07; 95% Cl: 1.07 0.87-1.31; P=0.553. Regarding rehospitalization rates, no significant difference was observed at a 3- month follow-up: aOR, 1.22; 95% Cl: 1.03-1.42; P=0.015. Interestingly, patients admitted with statin therapy were significantly associated with higher odds of hospitalization during the 12-month follow-up period: aOR, 1.42; 95% Cl: 1.21-1.66; P<0.001. CONCLUSION: Prior statin use was associated with a lower risk of in-hospital mortality and rehospitalization. However, there were no significant differences in all-cause mortality between the two groups at both 3- and 12-month follow-ups. While rehospitalization rates at the 3-month follow-up showed higher odds of rehospitalization at the 12-month follow-up. Prior statin therapy appears to influence both in-hospital mortality and long-term rehospitalization outcomes in a Middle Eastern patient population.
De Luca G, Algowhary M, Uguz B
… +89 more, Oliveira DC, Ganyukov V, Zimbakov Z, Cercek M, Jensen LO, Huan Loh P, Calmac L, Roura I Ferrer G, Quadros A, MIlewski M, Di Uccio FS, Von Birgelen C, Versaci F, Ten Berg J, Casella G, Wong Sung Lung A, Kala P, Díez Gil JL, Carrillo X, Dirksen MT, Manuel Becerra-Munoz V, Kang-Yin Lee M, Arifa Juzar D, de Moura Joaquim R, Paladino R, Milicic D, Davlouros P, Bakraceski N, Zilio F, Donazzan L, Kraaijeveld A, Galasso G, Arpad L, Marinucci L, Guiducci V, Menichelli M, Scoccia A, Hatice Yamac A, Ugur Mert K, Rios XF, Kovarnik T, Kidawa M, Moreu J, Vincent F, Fabris E, Martinez-Luengas IL, Boccalatte M, Bosa Ojeda F, Arellano-Serrano C, Caiazzo G, Cirrincione G, Kao HL, Sanchis Fores J, Vignali L, Pereira H, Manzo-Silbermann S, Ordonez S, Arat Ozkan A, Scheller B, Lehtola H, Teles R, Mantis C, Antti Y, Brum Silveira JA, Zoni R, Bessonov I, Savonitto S, Kochiadakis G, Alexopoulos D, Uribe CE, Kanakakis J, Faurie B, Gabrielli G, Gutierrez Barrios A, Bachini JP, Rocha A, Chor-Cheung Tam F, Rodriguez A, Lukito AA, Saint-Joy V, Pessah G, Cortese G, Parodi G, Burgadha MA, Kedhi E, Lamelas P, Suryapranata H, Nardin M, Verdoia M
BACKGROUND: Several scores have been developed to facilitate risk stratification and early discharge following primary angioplasty, particularly the Zwolle Risk Score (ZRS). However, validation in large-sized studies is...BACKGROUND: Several scores have been developed to facilitate risk stratification and early discharge following primary angioplasty, particularly the Zwolle Risk Score (ZRS). However, validation in large-sized studies is still lacking. Therefore, the aim of the current study was to validate the use of the ZRS in a contemporary global population, including patients who were treated during the SARS-CoV-2 pandemic and enrolled in a large intercontinental observational study. METHODS: The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving primary PCI centers from Europe, Latin America, South-East Asia, and NorthAfrica, including patients treated from March 1st until June 30th, in 2019 and 2020]. ZRS was calculated for each patient. The patients were additionally categorized according to the following values of the ZRS [≤3; 4-6; 7-9; ≥10]. Our study outcomes were in-hospital and 30-day mortality. The discriminatory capacity of the ZRS was assessed by the area under the ROC curve [c statistic] as an index of model performance. RESULTS: Our population is represented by 16084 STEMI patients undergoing mechanical reperfusion enrolled in 109 centers. The score showed a very good performance in the predicting mortality both in-hospital [AUC=0.83 [0.82-0.85], p<0.0001] and at 30- day follow-up [AUC=0.82 [0.81-0.84, p<0.0001]. The results were confirmed when the ZRS was separately applied to patients treated in 2019 and 2020, with good stability across time. ZRS was able to identify a large cohort [n=10672, 66.3%] of low-risk patients [score ≤3] with a very low mortality rate at 2 days [1%] and between 3 and 10 days [0.7%], with a very good negative predictive value for in-hospital [98.3%] and 30-day mortality [97.7%], with similar results in 2019 and 2020. CONCLUSION: This study is the first to demonstrate the good prognostic performance of the ZRS in a large-scale contemporary global multicenter validation set. Similar results were obtained both in the pre-pandemic and the COVID-19 era. ZRS ≤3 identified a very low-risk population that could be discharged early, even during the COVID-19 pandemic, with expected advantages in the availability of hospital beds and nursing staff, costs of medical care, and in-hospital risk of contagion.
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with multiorgan and system involvement, including the Cardiovascular (CV) system. Cardiac involvement in these patients is frequent and most often asympt...Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with multiorgan and system involvement, including the Cardiovascular (CV) system. Cardiac involvement in these patients is frequent and most often asymptomatic, at least in the early stages. It includes accelerated atherosclerosis, premature Coronary Artery Disease (CAD), and a high risk of CV complications. The risk of developing CV Disease (CVD) in SLE is linked not only with classical CV risk factors but also with disease-specific factors, like the degree of activity, autoantibodies, organ damage, and type of therapy. Clinical presentation comprises several clinical manifestations ranging from angina to acute Myocardial Infarction (MI) and Sudden Cardiac Death (SCD). The leading cause of death in SLE patients is from CVD due to accelerated atherosclerosis, which often has a more rapid progression compared with the general population. The CV risk in SLE is greater when antiphospholipid antibodies are present. Regarding diagnosis, apart from relevant blood tests, the simplest and readily available diagnostic test, echocardiography, with its contemporary techniques that include global longitudinal strain, is needed to provide a more thorough cardiac evaluation and allow for early management. These aspects of the disease, together with issues regarding phenotypes, biomarkers, neonatal lupus, heart block, SLE-related CV ailments such as coronary artery disease (CAD), myocarditis, valvular heart disease, and the antiphospholipid syndrome, as well as diagnostic modalities, drug and interventional therapies, and current relevant guidelines are all thoroughly reviewed and discussed in this article.
UNLABELLED: As a conflict has arisen among the authors, the article has been withdrawn at the request of the authors of the journal Current Vascular Pharmacology. The publisher sincerely apologizes to the readers of the...UNLABELLED: As a conflict has arisen among the authors, the article has been withdrawn at the request of the authors of the journal Current Vascular Pharmacology. The publisher sincerely apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.