American Journal of Cardiovascular Drugs最新文献

{"title":"Association Between Colchicine Use and Clinical Outcomes Post Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.","authors":"Vikash Jaiswal, Muhammad Hanif, Hafsa Arshad Azam Raja, Sulochana Khadka, Novonil Deb, Yusra Mashkoor, Aymen Ahmed, Kripa Rajak, Arvind Kumar Jaiswal, Mohit Gupta, Sameer Hirji, Gregg C Fonarow, Arman Qamar","doi":"10.1007/s40256-026-00831-7","DOIUrl":"https://doi.org/10.1007/s40256-026-00831-7","url":null,"abstract":"<p><strong>Background: </strong>Colchicine has been shown to mitigate inflammation and reduce adverse cardiovascular events. However, evidence from clinical trials has been mixed regarding its efficacy in cardiovascular prevention among patients undergoing cardiac surgery.</p><p><strong>Objective: </strong>We aimed to evaluate the association between colchicine use and cardiovascular outcomes in patients undergoing cardiac surgery.</p><p><strong>Methods: </strong>We conducted a systematic literature search on various electronic databases for relevant studies from their inception until July 15, 2025. Randomized controlled trials (RCTs) with two arms-one with colchicine as an intervention and the other with placebo-in patients undergoing cardiac surgery were included. Risk ratios (RRs) and weighted mean differences (WMDs), along with 95% confidence intervals (CIs), were pooled using a random-effects model. A p value of < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>Nine RCTs with 2005 patients (990 in the colchicine group and 1015 in the placebo group) were included. The mean age was 62.8 years. Pooled analysis demonstrated that compared with placebo, colchicine was significantly associated with a reduction in the risk of postoperative atrial fibrillation (POAF) (RR 0.70 [95% CI 0.59-0.83], p < 0.001). However, between the groups, there was no statistically significant difference in the risk of all-cause mortality (ACM) (RR 0.81 [95% CI 0.39-1.69], p = 0.57, I² = 0%), stroke (RR 1.86 [95% CI 0.48-7.12], p = 0.37), and permanent pacemaker implantation (PPM) (RR 1.36 [95% CI 0.08-22.44], p = 0.83). Length of hospital stay, which was exploratory, was significantly shorter in the colchicine group (WMD - 1.16 [95% CI - 1.89 to - 0.44], p < 0.01) compared to placebo.</p><p><strong>Conclusion: </strong>This meta-analysis demonstrates that colchicine appears to reduce the risk of POAF. However, it does not significantly affect the risks in terms of PPM, ACM, or stroke.</p><p><strong>Registration: </strong>PROSPERO identifier no. CRD420251117966.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149369786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Intravenous Nicotinamide Adenine Dinucleotide on Left Ventricular Function After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: A Randomized Controlled Trial.","authors":"Xiaofan Yu, Jiaoyu Cao, Qizhi Xu, Ben Hu, Yue Hu, Dongbiao Yu, Jiawei Wu, Likun Ma","doi":"10.1007/s40256-026-00826-4","DOIUrl":"https://doi.org/10.1007/s40256-026-00826-4","url":null,"abstract":"<p><strong>Background: </strong>Despite timely reperfusion and guideline-directed therapies, the recovery of left ventricular function after ST-segment elevation myocardial infarction (STEMI) remains suboptimal. Adjunctive metabolic therapy may enhance post-infarction cardiac repair. Nicotinamide adenine dinucleotide (NAD⁺), a key regulator of cellular bioenergetics and redox homeostasis, has cardioprotective effects in experimental ischemia-reperfusion injury. However, its clinical impact in patients undergoing primary percutaneous coronary intervention (PCI) remains unclear.</p><p><strong>Methods: </strong>In this prospective, randomized, placebo-controlled trial, 120 patients with STEMI undergoing primary PCI were assigned to receive intravenous NAD⁺ (10 mg/day) or placebo for 7 days, in addition to standard medical therapy. The primary endpoint was the left ventricular ejection fraction (LVEF) at 30 days. The secondary endpoints included N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at 7 and 30 days, echocardiographic parameters at 30 days, and major adverse cardiac and cerebrovascular events (MACCE) at 6 months.</p><p><strong>Results: </strong>At 30 days, the NAD⁺ group demonstrated a modest but significant improvement in LVEF compared with the placebo group (56.32 ± 8.04% vs. 53.37 ± 8.12%, p = 0.048). NT-proBNP levels were lower in the NAD⁺ group at follow-up. However, findings for LV remodeling parameters were mixed, and no significant between-group difference was observed in 6-month MACCE rates.</p><p><strong>Conclusions: </strong>Short-term intravenous NAD⁺ therapy following primary PCI improved left ventricular systolic function and reduced NT-proBNP levels in patients with STEMI. These findings suggest that restoring NAD⁺ availability may facilitate post-ischemic cardiac recovery, potentially through mechanisms related to mitochondrial energy metabolism and NAD⁺-dependent stress-response signaling. Larger trials are required to confirm its long-term clinical benefits and elucidate the underlying biological pathways.</p><p><strong>Registration: </strong>Chinese Clinical Trial Registry identifier number ChiCTR2200059333.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149294091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Conventional Antihypertensives: RNA Interference, Endothelin Antagonism, and Aldosterone-Synthase Inhibition in the Current Therapeutic Landscape.","authors":"Giovanni Vincenzo Gaudio, Giuseppe Derosa, Giuseppe De Angelis, John Tremamondo, Alessandro Lupi","doi":"10.1007/s40256-026-00830-8","DOIUrl":"https://doi.org/10.1007/s40256-026-00830-8","url":null,"abstract":"<p><p>Hypertension is the leading modifiable cardiovascular risk factor, yet long-term adherence to antihypertensive therapy remains suboptimal. RNA-based approaches targeting hepatic angiotensinogen (AGT) have emerged as an attractive strategy for upstream renin-angiotensin-aldosterone system suppression and warrant a timely, focused review of the field. PubMed/MEDLINE, ClinicalTrials.gov and the most relevant scientific and academic databases were searched up to February 2026 to draft a narrative review of peer-reviewed clinical trials, pivotal translational studies, contemporary hypertension guidelines, and official regulatory documents relevant to innovative antihypertensive treatments, such as antisense AGT suppression (zilebesiran), endothelin antagonism (aprocitentan), and aldosterone-synthase inhibition (baxdrostat). Zilebesiran demonstrated durable blood-pressure lowering in monotherapy (KARDIA-1: placebo-adjusted ambulatory systolic blood pressure (BP) - 16.7 mmHg at month 3) and as add-on therapy (KARDIA-2: greatest effect with indapamide background). KARDIA-3 extended evaluation to a higher-risk, heavily medicated population, in which the primary endpoint was not met. The ongoing ZENITH outcomes trial will determine whether AGT silencing reduces hard cardiovascular end-points. Aprocitentan reduced office and ambulatory systolic BP in resistant hypertension (PRECISION trial) and has received regulatory approval in the USA, EU, and UK, with specific monitoring requirements for fluid retention and hematological effects. Baxdrostat demonstrated selective aldosterone-synthase inhibition with meaningful BP reductions across two phase II trials. RNA interference targeting AGT represents one of the most advanced disease-modifying platforms in hypertension, alongside the already-approved endothelin antagonism and the emerging aldosterone synthase inhibition strategy. The available evidence supports cautious optimism and continued translational investment, but not premature adoption into routine practice.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Trends and Predictors of P2Y12 Inhibitor Selection and Switching Following Percutaneous Coronary Intervention in Acute Coronary Syndrome Patients.","authors":"Young Eun Shin, Arun Kumar, Anne Metzger, Patricia Wigle, Jeff Jianfei Guo, Ana L Hincapie","doi":"10.1007/s40256-026-00827-3","DOIUrl":"https://doi.org/10.1007/s40256-026-00827-3","url":null,"abstract":"<p><strong>Introduction: </strong>Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is standard care after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). While ticagrelor provides potent ischemic protection, bleeding risk, tolerability, and treatment access may influence real-world P2Y12 inhibitor selection and ticagrelor-to-clopidogrel switching. Contemporary data describing P2Y12 inhibitor selection and recorded switching patterns across ACS subtypes remain limited.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the TriNetX electronic health record database to identify adults hospitalized with ACS who underwent PCI between 2013 and 2021. Patients initiating ticagrelor or clopidogrel within 14 days post-PCI were included and categorized by initial P2Y12 inhibitor. Temporal trends were assessed annually. Multivariable logistic regression identified predictors of ticagrelor initiation. Among ticagrelor initiators, switching to clopidogrel within 365 days was evaluated, including cumulative switching at prespecified landmark time points.</p><p><strong>Results: </strong>Among 57,619 patients, 38.2% initiated ticagrelor and 61.8% clopidogrel. Ticagrelor initiation increased over time but remained less common overall. Ticagrelor initiation was more likely among younger patients, males, those with ST-elevation myocardial infarction, drug-eluting stent use, lower bleeding risk, and lower comorbidity burden, with substantial geographic variation observed. Among ticagrelor initiators, 31.4% had a recorded switch to clopidogrel within 1 year. Observed cumulative switching was 17.0% at 30 days, 23.0% at 90 days, 26.8% at 180 days, and 31.4% at 365 days. The median time to switch was not estimable because fewer than 50% of patients switched during follow-up.</p><p><strong>Conclusion: </strong>In this real-world cohort of patients with ACS undergoing PCI, initial P2Y12 inhibitor selection varied by demographic, clinical, procedural, and geographic characteristics. Recorded ticagrelor-to-clopidogrel switching was common but should not be interpreted uniformly as intentional clinical de-escalation. These findings highlight the need for future research to clarify reasons for switching and to inform individualized P2Y12 inhibitor treatment strategies in routine practice.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beta-Blockers for the Treatment of Arrhythmias: Which Drug for Which Arrhythmia? A State-of-the-Art Narrative Review.","authors":"Lucian Muresan, Gabriel Cismaru, Stefan Lucian Popa, Radu Rosu, Gabriel Gusetu, Mihai Puiu, Razvan Olimpiu Mada, Crina Muresan, Ronan Le Bouar, Serban Schiau, Charline Daval, Jacques Levy, Raphael Pedro Martins","doi":"10.1007/s40256-026-00828-2","DOIUrl":"https://doi.org/10.1007/s40256-026-00828-2","url":null,"abstract":"<p><p>Beta-blockers are among the most widely prescribed drugs in the management of both supraventricular and ventricular arrhythmias, and they are frequently regarded as a homogeneous pharmacological class. They are not. The agents in current use differ substantially in beta1-receptor selectivity, lipophilicity, half-life, route of administration, intrinsic sympathomimetic activity, and ancillary properties, and arrhythmias themselves differ in mechanism, adrenergic dependence, anatomical origin, and structural substrate. This narrative review examines whether these pharmacological differences translate into clinically meaningful differences in efficacy and utility, asking not only whether a beta-blocker should be used but which one should be used. Evidence was drawn from a targeted search of PubMed, Web of Science, Scopus, Ovid, Embase, and the Cochrane Library, with priority given to randomized controlled trials, meta-analyses, large registries, and contemporary society guidelines, and was synthesized qualitatively by arrhythmia type. A class effect is apparent for many indications, particularly rate control in atrial fibrillation and atrial flutter, where metoprolol, bisoprolol, and carvedilol perform broadly similarly and the choice is driven mainly by comorbidity and tolerability. Drug-specific differences emerge in three settings. In adrenergically mediated inherited syndromes, namely catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, nonselective agents and especially nadolol are clearly superior to beta1-selective agents, and the same principle appears to extend to ventricular electrical storm, in which propranolol has outperformed metoprolol in a randomized comparison. In acute care, pharmacokinetics dominate, and the ultra-short-acting agents esmolol and landiolol permit a degree of titration that longer-acting drugs cannot match. In patients with heart failure and reduced ejection fraction, carvedilol, metoprolol succinate, and bisoprolol should be preferred irrespective of arrhythmia subtype because of their established mortality benefit. Conversely, beta1-selective agents, including the highly selective agent nebivolol, improve tolerability in bronchospastic disease, although this reflects respiratory tolerability rather than any demonstrated antiarrhythmic advantage, and beta-blockers have little role in Brugada syndrome or in bradycardia-dependent acquired torsades de pointes. Beta-blockers should therefore not be treated as interchangeable. Selection should integrate arrhythmic mechanism, structural substrate, and patient characteristics, and head-to-head trials remain conspicuously scarce.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 Inhibitors in Cardiovascular-Kidney-Metabolic Syndrome: Drugs Unifying Heart, Kidney, and Metabolism Pharmacotherapy.","authors":"Valentina Okhovat, Kamela Lybeshari, Luigi X Cubeddu, Genevieve Hale","doi":"10.1007/s40256-026-00829-1","DOIUrl":"https://doi.org/10.1007/s40256-026-00829-1","url":null,"abstract":"<p><p>Cardiovascular-kidney-metabolic syndrome describes a complex interplay between cardiovascular disease, chronic kidney disease, and metabolic disorders. Recent randomized controlled trials have demonstrated beneficial effects of SGLT2 inhibitors in patients with this multifaceted condition. This review aims to critically evaluate the available evidence supporting the role of SGLT2 inhibitors in patients with cardiovascular-kidney-metabolic syndrome and familiarize healthcare providers with the evidence surrounding significant renal and cardiac benefits of SGLT2 inhibitors. A comprehensive narrative literature review was conducted using PubMed. Eligible studies included randomized controlled trials, systematic reviews, and meta-analyses published in English between 2018 and 2025, focusing on SGLT2 inhibitors in the context of cardio-renal syndrome and cardio-kidney-metabolic syndrome. Multiple landmark trials have shown that SGLT2 inhibitors significantly reduce the risk of chronic kidney disease progression, MACE, and hospitalization for HF. These benefits were seen in patients both with and without type 2 diabetes. Importantly, SGLT2 inhibitors such as canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin were well tolerated, though caution is advised in volume-depleted patients or those at risk for genitourinary infections. Positive effects, ranging from glycemic control to renoprotective and cardioprotective properties, support SGLT2 inhibitors as first-line therapy in improving clinical outcomes and quality of life in patients affected by this interconnected disease spectrum.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein(a): Cardiovascular Risk and Emerging Targeted Therapies.","authors":"José Pablo Miramontes González","doi":"10.1007/s40256-026-00825-5","DOIUrl":"10.1007/s40256-026-00825-5","url":null,"abstract":"<p><p>Lipoprotein(a) [Lp(a)] is a genetically determined, low-density lipoprotein-like particle that has emerged as an important and independent contributor to atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Elevated Lp(a) concentrations, defined as approximately 125 nmol/L (≥ 50 mg/dL) by most consensus thresholds, affect an estimated 20% of the general population and confer lifelong inherited cardiovascular risk that is not adequately captured by standard lipid panels. Epidemiological, observational and genetic studies consistently show that elevated Lp(a) concentrations are associated with increased risk of coronary heart disease, myocardial infarction, ischemic stroke, peripheral artery disease and calcific aortic valve stenosis. Unlike low-density lipoprotein (LDL) cholesterol, Lp(a) levels remain relatively stable throughout life and are only minimally influenced by lifestyle interventions or most conventional lipid-lowering therapies. This creates a clinically relevant therapeutic gap, particularly in patients with premature cardiovascular disease, recurrent events despite optimal LDL cholesterol control, or otherwise unexplained residual risk. Traditional lipid-lowering strategies remain essential to reduce global cardiovascular risk, but they have limited ability to directly modify Lp(a)-mediated risk. PCSK9 inhibitors and inclisiran produce modest (approximately 20-30%) Lp(a) reductions, and lipoprotein apheresis may be useful in highly selected patients, but none represents a broadly applicable Lp(a)-specific therapy. Recent advances have changed this landscape. Antisense oligonucleotides, small interfering RNA therapies and oral small-molecule inhibitors have demonstrated profound and durable Lp(a) reductions, frequently exceeding 80-100% with small interfering RNA (siRNA)-based agents (olpasiran, zerlasiran, lepodisiran), up to 80% with the antisense oligonucleotide pelacarsen, and up to 85% with the oral small-molecule muvalaplin, in phase 1 and phase 2 clinical trials. However, the central question remains whether pharmacological Lp(a) lowering translates into fewer cardiovascular events. Current evidence supports strong biological efficacy, but definitive proof of clinical benefit awaits ongoing randomized cardiovascular outcomes trials, including Lp(a)HORIZON (pelacarsen), OCEAN(a)-Outcomes (olpasiran) and ACCLAIM-Lp(a) (lepodisiran). This narrative review summarizes the biology and epidemiological relevance of Lp(a), quantifies its association with cardiovascular events, reviews the effect of traditional lipid-lowering therapies on Lp(a) and critically discusses emerging Lp(a)-targeted treatments and future directions.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vutrisiran in Transthyretin Amyloidosis: A Narrative Review.","authors":"Kamela Lybeshari, Huy Pham, Genevieve Hale","doi":"10.1007/s40256-026-00824-6","DOIUrl":"https://doi.org/10.1007/s40256-026-00824-6","url":null,"abstract":"<p><p>This report describes vutrisiran (Amvuttra^®), a novel double-stranded small interfering ribonucleic acid (siRNA)-N-acetylgalactosamine (GalNAc) conjugate. A narrative literature review was conducted using a secondary database, PubMed, from 2018 to 2025. Articles were limited to those written in English. Inclusion criteria consisted of randomized controlled trials and systematic reviews that analyzed the use of vutrisiran to treat amyloidosis. Other drug information resources, including the package inserts and UpToDate, were also utilized for general information. Two phase 3 publications were included in this report. Vutrisiran significantly improved neuropathy, quality of life, and functional measures in patients with hereditary transthyretin amyloidosis with polyneuropathy. Additionally, vutrisiran reduced the risk of death and recurrent cardiovascular events, preserved functional capacity and quality of life, and slowed New York Heart Association (NYHA) class progression compared with placebo. A favorable safety profile was also found in landmark trials. Vutrisiran is a therapeutic option for amyloidosis, directly targeting the underlying pathogenic mechanism through RNA interference. Clinical trials have demonstrated a reduction in transthyretin protein levels, slowing neuropathic and cardiac disease progression, and improving functional and quality-of-life outcomes. Ongoing research on long-term outcomes is still to be elucidated.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of β-Blocker Therapy on Peak VO₂ in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis.","authors":"Juliana Giorgi, Pedro Gomes Batista, Milena Dall Witt de Souza, Giulia Gaelzer, Larissa Lucena, Juan Peres de Oliveira, Ramon Huntermann, Maria Eduarda Molinari, Caroline O Fischer-Bacca","doi":"10.1007/s40256-026-00822-8","DOIUrl":"https://doi.org/10.1007/s40256-026-00822-8","url":null,"abstract":"<p><strong>Background: </strong>Heart failure with preserved ejection fraction (HFpEF) accounts for over half of all heart failure cases and remains without definitive therapy. β-blockers (BB) are frequently prescribed, often extrapolated from HFrEF management, but their benefit in HFpEF is uncertain. By reducing heart rate and contractility, BB may further limit exercise capacity in patients whose cardiac output is rate-dependent.</p><p><strong>Purpose: </strong>To systematically evaluate the impact of BB therapy on functional capacity, quality of life, and natriuretic peptide levels in patients with HFpEF.</p><p><strong>Methods: </strong>A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO CRD420251229202). PubMed, Embase, and Cochrane databases were searched through November 2025 for randomized and observational studies assessing BB therapy or withdrawal in HFpEF. The primary end point was peak oxygen consumption (VO₂ peak). Secondary outcomes included Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Mean or standardized mean differences (95% CI) were pooled using a random-effects model.</p><p><strong>Results: </strong>Five studies comprising 803 patients (525 on BB therapy) were included. BB use was associated with a significant reduction in VO₂ peak (MD = -2.02 mL·kg⁻¹·min⁻¹; 95% CI -3.26 to -0.79; p < 0.01). No significant differences were found in MLHFQ scores (SMD = 0.32; 95% CI -0.57 to 1.21; p = 0.48) or NT-proBNP levels (MD = 130.71 pg/mL; 95% CI -143.27 to 404.69; p = 0.35).</p><p><strong>Conclusions: </strong>BB therapy was associated with lower objective peak VO₂ without consistent effects on patient-reported outcomes or natriuretic peptides.</p><p><strong>Trial registry: </strong>Prospero registration: CRD420251229202.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zilebesiran in Hypertension: Reversibility, Acute Illness, and Therapeutic Flexibility.","authors":"Lucas Maciel de Almeida Corrêa, Gabriel Rian Mazur, Clara Belo Gamon Santiago, Alexandre de Assis Barbosa, Ivan Felipe Dutra Júnior, Gabriel Costa de Santana, Luiggi Kevin Virgino Brandão, Yan Roberth Delmiro Silva, Letícia Esteves Dante","doi":"10.1007/s40256-026-00823-7","DOIUrl":"https://doi.org/10.1007/s40256-026-00823-7","url":null,"abstract":"<p><p>Zilebesiran is an investigational RNA interference therapeutic that lowers blood pressure by silencing hepatic angiotensinogen, thereby offering sustained antihypertensive activity with infrequent dosing in selected ambulatory populations. This profile is attractive for long-term blood pressure control, but it also raises an unresolved clinical question: how should acute illness be managed when upstream renin-angiotensin system suppression cannot be rapidly attenuated? In this Current Opinion, we place that question in perspective using available trial data, cardiorenal physiology, and acute-care literature. Early-phase studies established that zilebesiran produces sustained angiotensinogen suppression and blood pressure reduction, while also showing that the antihypertensive response is modulated by dietary sodium intake and background renin-angiotensin-aldosterone system blockade. Phase 2 studies then confirmed antihypertensive efficacy in clinically stable outpatient populations, and KARDIA-3 extended evaluation to patients with uncontrolled hypertension and established or high cardiovascular risk receiving multiple antihypertensive agents; however, the study did not meet its prespecified multiplicity-adjusted threshold for statistical significance at month 3. The concern is not that harm has been demonstrated, but that prolonged angiotensinogen silencing may reduce short-term therapeutic flexibility during sepsis, perioperative stress, acute heart failure, marked volume depletion, or hyperkalemia-settings in which clinicians often rely on temporary adjustment of oral renin-angiotensin-aldosterone system inhibitors. Early reversal strategies are conceptually important, but current approaches appear better suited to planned de-escalation than emergency rescue. Future work should define vulnerable phenotypes, clarify whether acute-care pathways require protocol adaptation, and determine how reversibility can be operationalized as phase 3 development advances.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}