American Journal of Cardiovascular Drugs最新文献

{"title":"Lipoprotein(a): Cardiovascular Risk and Emerging Targeted Therapies.","authors":"José Pablo Miramontes González","doi":"10.1007/s40256-026-00825-5","DOIUrl":"https://doi.org/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}

{"title":"Evaluating the Impact of Stair Climbing on Cardiovascular Risk Reduction: A Systematic Review and Meta-analysis.","authors":"Sophie Paddock, Rathna Veerni, U Bhalraam, James Meng, Emily Dawson-Plincke, Vasiliki Tsampasian, Vassilios Vassiliou","doi":"10.1007/s40256-026-00811-x","DOIUrl":"10.1007/s40256-026-00811-x","url":null,"abstract":"<p><strong>Background/objectives: </strong>Physical inactivity causes a significant burden from cardiovascular disease worldwide. As sedentary behaviours become increasingly prevalent, there is a growing imperative to explore practical strategies to mitigate cardiovascular risk. This systematic review and meta-analysis aimed to evaluate the association between physical activity in the form of stair climbing and cardiovascular risk.</p><p><strong>Methods: </strong>A systematic search of the PubMed and Embase databases was conducted from inception until 8 April 2025. Randomised controlled trials or observational studies including stair climbing as a variable were included. The outcomes of interest were cardiovascular mortality and incidence of cardiovascular disease including myocardial infarction, ischaemic stroke and heart failure. Statistical analyses were conducted using the Review Manager (RevMan) software.</p><p><strong>Results: </strong>The database search yielded 1873 studies, out of which, nine studies with 480,479 patients were included in the analysis. The pooled analysis of five studies and 455,619 patients revealed that stair climbing was associated with a significant reduction in cardiovascular mortality (relative risk [RR] 0.61, 95% confidence interval [CI] 0.48-0.79, p = 0.0002). Further analysis of these studies revealed that stair climbing was also associated with a significant reduction in all-cause mortality (RR 0.76, 95% CI 0.62-0.94, p = 0.01). Morbidity was also associated with stair climbing.</p><p><strong>Conclusions: </strong>Physical activity in the form of stair climbing is associated with a reduced risk of cardiovascular and all-cause mortality. These findings highlight the importance of promoting everyday activities, even within the workplace and home, to foster healthier lifestyles and mitigate the risks associated with cardiovascular diseases.</p><p><strong>Registration: </strong>PROSPERO identifier no. CRD42023490479.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720585","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":"Antihypertensive Efficacy and Safety of Angiotensin Receptor Blockers (ARBs) with and without Inverse Agonism: A Systematic Review and Network Meta-analysis.","authors":"Jing Liu, Jialu Geng, Jiakun Liu, Lei Hu, Huimin Du, Ivan Tjong A Hung, Jia Fang","doi":"10.1007/s40256-026-00813-9","DOIUrl":"https://doi.org/10.1007/s40256-026-00813-9","url":null,"abstract":"<p><strong>Introduction: </strong>While not all angiotensin receptor blockers (ARBs) exhibit inverse agonistic activity, certain ARBs with this property may offer greater potential for blood pressure (BP) reduction compared with ARBs without inverse agonism. This study aimed to evaluate the antihypertensive efficacy and safety of ARBs with or without inverse agonism.</p><p><strong>Methods: </strong>A systematic literature review and network meta-analysis identified randomized clinical trials (RCTs) of first-line monotherapy for mild-to-moderate hypertension: azilsartan medoxomil (AZL-M), candesartan, olmesartan, losartan, valsartan, telmisartan, irbesartan, allisartan isoproxil, sacubitril/valsartan, sacubitril/allisartan, or placebo. Treatments were grouped as ARBs with or without inverse agonism, angiotensin receptor neprilysin inhibitors (ARNIs), and placebo. AZL-M was separately analyzed as part of ARBs with inverse agonism. BP changes and adverse events (AEs) were assessed.</p><p><strong>Results: </strong>Of 2659 RCTs screened, 23 studies were analyzed. ARBs with inverse agonism demonstrated superior systolic BP and diastolic BP reductions compared with ARBs without inverse agonism, ARNIs, and placebo. When analyzed separately, AZL-M significantly outperformed ARBs without inverse agonism in systolic BP and diastolic BP reduction and was superior to other ARBs with inverse agonism in systolic BP reduction. Surface under the cumulative ranking curves (SUCRA) indicated AZL-M had the highest probability of being the best treatment for systolic BP (98%) and diastolic BP (95%) reduction.</p><p><strong>Conclusions: </strong>This study supports that ARBs with inverse agonism, especially AZL-M, have a better BP-lowering efficacy compared with ARBs without inverse agonism and ARNIs, while maintaining favorable safety profiles. Future research is encouraged to explore the effects on long-term outcomes, combination therapies, and safety in diverse populations.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697006","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":"Adherence and Healthcare Costs Associated with Single-vs Free-Pill Combination of Perindopril-Based Antihypertensive Medications: An 11-Year Follow-Up, Real-World Evidence.","authors":"Gianluigi Savarese, Ana-Maria Vintila, Luca Degli Esposti, Melania Dovizio, Julien Magne, Marta Nugnes, Chiara Veronesi, Jacek Wolf, Stefano Masi","doi":"10.1007/s40256-026-00818-4","DOIUrl":"https://doi.org/10.1007/s40256-026-00818-4","url":null,"abstract":"<p><strong>Background: </strong>Short-term studies have demonstrated that single-pill combinations (SPCs) improve adherence, reduce hypertension-related complications, and lower costs; however, long-term benefits remain unclear. This study compared adherence, healthcare resource utilization (HCRU), and costs over 11 years in patients treated with SPCs versus free-pill combinations (FPCs) of antihypertensive drugs in routine Italian practice.</p><p><strong>Methods: </strong>We analyzed a large administrative dataset (2010-2022) covering approximately 7 million Italian citizens. Adults initiating perindopril (PER)-based SPC or FPC with amlodipine and/or indapamide were included. PER-based therapies were selected because their SPCs were among the first marketed in Italy, allowing for extended follow-up. Adherence was measured by proportion of days covered (PDC), with high adherence defined as PDC ≥ 80%.</p><p><strong>Results: </strong>Among 24,476 patients (mean age: 64.6 years; 59.7% male), 92.6% received SPCs, and 6.0% FPCs. High adherence was observed in 75.5% of SPC users compared with 32.0% of FPC users. SPC users had fewer all-cause hospitalizations and outpatient visits (both p < 0.001). Average annual healthcare costs were €242.96 lower for SPC users (95% CI €55.03-€430.89; p < 0.05), with significant reductions in costs related to all-cause and cardiovascular-related hospital admissions (p < 0.001).</p><p><strong>Conclusions: </strong>In this long-term, real-world study, SPC use was associated with better adherence, reduced HCRU, and lower healthcare costs compared with FPC regimens. These economic benefits were evident within 1 year and may yield substantial long-term savings for national health systems, given the high prevalence and chronic nature of hypertension.</p>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683148","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":"Comparative Effectiveness of Sacubitril/Valsartan Versus Sodium-Glucose Cotransporter 2 Inhibitors among Patients with Heart Failure with Reduced Ejection Fraction with or without Diabetes: A Cohort Study","authors":"Munaza Riaz,&nbsp;Steven M. Smith,&nbsp;David E. Winchester,&nbsp;Eric A. Dietrich,&nbsp;Haesuk Park","doi":"10.1007/s40256-026-00819-3","DOIUrl":"10.1007/s40256-026-00819-3","url":null,"abstract":"<div><h3>Background</h3><p>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and sacubitril/valsartan (SAC/VAL), an angiotensin receptor-neprilysin inhibitor, are both US Food and Drug Administration-approved and guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF). While each has demonstrated significant reductions in cardiovascular morbidity and mortality, direct comparative evidence remains limited, particularly in relation to patients’ diabetes status.</p><h3>Objective</h3><p>To compare the effectiveness of SAC/VAL versus SGLT2i in preventing HF-related and all-cause hospitalizations among patients with HFrEF, with or without diabetes, using real-world data from the MarketScan^® Research databases.</p><h3>Methods</h3><p>This new-user, active-comparator cohort study using MarketScan^® Commercial and Medicare databases (2019–2023) identified patients with HFrEF by using International Classification of Diseases codes. Patients who initiated SAC/VAL or SGLT2i treatment were included, with the index date defined as the first prescription fill. Continuous health plan enrollment ≥ 6 months prior to HFrEF diagnosis through the index date was required. To balance baseline characteristics between groups, we applied stabilized inverse probability of treatment weighting (IPTW). Cox proportional hazards models compared risks of HF-related and all-cause hospitalizations in cohort analyses defined by diabetes status, diagnosis, and antidiabetic medications.</p><h3>Results</h3><p>After IPTW, the study included 7406 patients initiating SAC/VAL and 5101 patients initiating SGLT2i. Among patients with diabetes, there were no significant differences in the risks of HF-related hospitalization (adjusted hazard ratio [aHR] 1.13, 95% confidence interval [CI] 0.98–1.30) or all-cause hospitalization (aHR 0.99, 95% CI 0.90–1.09) between medication groups. In contrast, among patients without diabetes, initiation of SAC/VAL was associated with significantly lower risks of HF-related hospitalization (aHR 0.65, 95% CI 0.56–0.76) and all-cause hospitalization (aHR 0.69, 95% CI 0.62–0.77).</p><h3>Conclusions</h3><p>In a real-world cohort of patients with HFrEF and without diabetes, but not those with diabetes, SAC/VAL initiation was associated with reduced risks of HF-related and all-cause hospitalizations compared with SGLT2i initiation. These findings provide supportive evidence that may inform clinicians when selecting therapy for patients with HFrEF.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"26 5","pages":"657 - 666"},"PeriodicalIF":3.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590297","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":"When Methods Matter: An Umbrella Review of Lorundrostat and the Impact of Analytical Decisions on Reported Blood Pressure and Safety Outcomes","authors":"Zeyad Elariny,&nbsp;Omar Salem,&nbsp;Mohamad Ashraf Salaheldin,&nbsp;Adham Ahmed,&nbsp;Farida Rabie,&nbsp;Maryam Mohamed Sayed,&nbsp;Mohamed Harish,&nbsp;Mohamed Ali,&nbsp;Selim Ahmed Eliwa,&nbsp;Mohammad Elshorbagy,&nbsp;Sara ElHarouni,&nbsp;Ahmed Abdelmeguid,&nbsp;Retaj Ahmed,&nbsp;Omnia Azmy Nabeh","doi":"10.1007/s40256-026-00817-5","DOIUrl":"10.1007/s40256-026-00817-5","url":null,"abstract":"<div><h3>Background</h3><p>Lorundrostat has emerged as a promising therapy for uncontrolled and/or resistant hypertension, with multiple systematic reviews and meta-analyses (SRMAs) evaluating its blood pressure effects and hyperkalemia risk. Despite drawing from identical trials, reported effect sizes varied markedly, warranting an umbrella review.</p><h3>Methods</h3><p>Conducted per the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420261358169), this umbrella review included SRMAs of lorundrostat in adults with uncontrolled hypertension. Pooled estimates for systolic blood pressure (SBP), diastolic blood pressure (DBP), and hyperkalemia risk were extracted and compared. Methodological quality was assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), and primary study overlap was quantified via corrected covered area (CCA).</p><h3>Results</h3><p>Ten SRMAs were included; seven focused exclusively on lorundrostat, all showing complete overlap (CCA = 100%). Despite this, substantial variability in pooled estimates was observed. Office SBP reductions ranged from − 7.35 to − 13.55 mmHg (the 95% confidence interval [CI] ranged between − 28.57 and 1.47), 24-h ambulatory SBP ranged from − 5.65 to − 7.45 mmHg (the 95% CI ranged between − 13.60 and 2.31), and DBP reductions were relatively consistent at approximately − 3 to − 4 mmHg, but with the 95% CI ranging between − 7.93 and 0.61. Variability stemmed primarily from differences in dose handling, outcome definitions, and analytical approaches. Lorundrostat was consistently associated with elevated hyperkalemia risk (RR 3.19–11.63), though severity was rarely stratified. Methodological quality was predominantly low to critically low.</p><h3>Conclusion</h3><p>Lorundrostat produces a modest blood pressure reduction in uncontrolled hypertension. Current evidence is constrained by methodological heterogeneity, limited long-term data, and inadequate safety reporting. Standardized analytical approaches and greater transparency are essential. The proposed effect size concordance index (ECI) may complement overlap metrics by capturing agreement in effect magnitude and precision; however, further validation is required.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"26 5","pages":"603 - 619"},"PeriodicalIF":3.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560644","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":"Aspirin Versus Clopidogrel as Single Antiplatelet Therapy After TAVI: A Propensity Score-Matched, Retrospective Analysis","authors":"Anastasios Apostolos,&nbsp;Konstantinos Konstantinou,&nbsp;Mohammed Allaf,&nbsp;Athanasios Sakalidis,&nbsp;Konstantinos Kalogeras,&nbsp;Ee Ling Heng,&nbsp;Simon Davies,&nbsp;Alison Duncan,&nbsp;Miles Dalby,&nbsp;Saeed Mirsadraee,&nbsp;Tarun Mittal,&nbsp;Aigul Baltabaeva,&nbsp;Tito Kabir,&nbsp;Mohammed Majid Akhtar,&nbsp;Robert Smith,&nbsp;Vasileios Panoulas","doi":"10.1007/s40256-026-00815-7","DOIUrl":"10.1007/s40256-026-00815-7","url":null,"abstract":"<div><h3>Background</h3><p>Current guidelines recommend single antiplatelet therapy (SAPT) with aspirin for most patients undergoing transcatheter aortic valve implantation (TAVI). However, the optimal choice of SAPT, namely aspirin or clopidogrel, remains uncertain. Our study aims to compare the impact of aspirin versus clopidogrel monotherapy on all-cause mortality in patients after TAVI.</p><h3>Methods</h3><p>Consecutive patients undergoing TAVI treated with single antiplatelet treatment (aspirin or clopidogrel) at two tertiary hospitals between 2012 and 2024 were studied. The primary endpoint was long-term survival over a median follow-up of 49.2 months. Propensity score matching was performed to adjust for baseline differences.</p><h3>Results</h3><p>Among 982 patients who underwent transcatheter aortic valve implantation and were treated with single antiplatelet therapy, 730 received aspirin, and 252 received clopidogrel. Patients treated with clopidogrel more frequently had a history of ischemic stroke and prior percutaneous coronary intervention and had lower preprocedural peak transvalvular velocity. Overall survival did not differ significantly between patients treated with aspirin and those with clopidogrel (101.0 months [52.7–149.3] versus 88.3 [49.3–127.3], <i>P</i> = 0.390). After propensity score matching, 141 pairs were identified, and long-term survival remained similar between the two groups (108.7 months [54.6–156.8] versus 88.3 [48.5–117.6], <i>P</i> = 0.204).</p><h3>Conclusions</h3><p>To the best of our knowledge, this is the largest study comparing aspirin versus clopidogrel following TAVI. Our analysis showed comparable long-term survival in patients treated with either aspirin or clopidogrel. Further randomized trials are required for the validation of our results.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"26 5","pages":"645 - 655"},"PeriodicalIF":3.2,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534863","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}