American Journal of Cardiovascular Drugs最新文献

{"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}

{"title":"Empagliflozin in STEMI Patients: A Randomized Controlled Trial on Left Ventricular Recovery and Cardiovascular Outcomes","authors":"Fatemeh Baharvand,&nbsp;Roxana Mehran,&nbsp;Francesca Maria Di Muro,&nbsp;Alieh Mohammadi,&nbsp;Mohammadreza Aghajankhah,&nbsp;Shiva Parvaneh,&nbsp;Niloufar Akbari Parsa,&nbsp;Soheil Hassanipour,&nbsp;Ehsan Aboutaleb,&nbsp;Yaser Jenab,&nbsp;Somayeh Bashiri Aliabadi","doi":"10.1007/s40256-026-00814-8","DOIUrl":"10.1007/s40256-026-00814-8","url":null,"abstract":"<div><h3>Background</h3><p>Sodium–glucose cotransporter 2 (SGLT2) inhibitors provide cardiovascular benefits in diabetes, but their role in the acute post-myocardial infarction (MI) setting is uncertain. This study evaluated the association of empagliflozin with left ventricular ejection fraction (LVEF) recovery and major adverse cardiac events (MACE) in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI).</p><h3>Methods</h3><p>In a single-center, double-blind, randomized, placebo-controlled trial, patients with STEMI were randomized to empagliflozin 10 mg or placebo daily for 40 days. The primary endpoint was change in left ventricular ejection fraction (LVEF) from baseline to day 40, with sample size calculated <i>a priori</i> based on data from the EMMY trial (minimum 27 per group; 53 per group enrolled). Major adverse cardiac events (MACE)—defined as cardiovascular death, myocardial infarction, or stroke—were assessed as a secondary exploratory endpoint.</p><h3>Results</h3><p>A total of 117 patients were randomized (59 empagliflozin, 58 placebo), of whom 106 completed follow-up and were analyzed (53 per group). Empagliflozin was associated with significantly greater LVEF recovery at day 40 (mean increase: 7.35% ± 6.11% versus 2.96% ± 5.49%; mean difference 4.39%, 95% CI 2.09–6.70%; <i>P</i> = 0.000272), which remained significant after adjustment for baseline LVEF, age, sex, and diabetes status (adjusted difference: 3.44%, 95% CI 1.22–5.66%; <i>P</i> = 0.003; Cohen’s <i>d</i> = 0.756). The benefit was numerically greater in younger and nondiabetic patients, though no subgroup interaction reached significance after multiplicity correction. MACE did not differ significantly between groups (3.8 versus 7.5%; <i>P</i> = 0.68), with no recurrent MI or stroke in either group. Adverse events were rare and comparable, with no diabetic ketoacidosis, amputation, or acute kidney injury observed.</p><h3>Conclusions</h3><p>In this preliminary single-center trial, empagliflozin was associated with significantly greater LVEF recovery in patients with STEMI after PCI, with effects robust to covariate adjustment, and without increasing adverse events. Although MACE was not significantly reduced—as expected given the study was not powered for hard clinical events—the LVEF improvement represents a promising early prognostic signal. These findings are applicable to lower-risk patients with STEMI with successful reperfusion and may not generalize to higher-risk patients with failed PCI or hemodynamic compromise. Larger, adequately powered, long-term multicenter trials are needed to confirm clinical benefits.</p><h3>Trial Registration</h3><p>Registered at the Iranian Registry of Clinical Trials identifier no. IRCT20220809055645N7.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"26 5","pages":"631 - 644"},"PeriodicalIF":3.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468354","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":"Food Effects on the Pharmacokinetics of Single Dose and Steady-State Ralinepag, a Novel Oral Prostacyclin Agonist, in Healthy Volunteers","authors":"Daniel Lachant,&nbsp;Cristian E. Botta,&nbsp;George Giannakoulas,&nbsp;Natalie Patzlaff,&nbsp;Scott Seaman,&nbsp;Meredith Broderick,&nbsp;Maria Guido,&nbsp;Søren Mellemkjær,&nbsp;Zeenat Safdar","doi":"10.1007/s40256-026-00807-7","DOIUrl":"10.1007/s40256-026-00807-7","url":null,"abstract":"<div><h3>Background</h3><p>Pulmonary arterial hypertension (PAH) is a rare, progressive disorder characterized by pathological pulmonary vascular remodeling leading to right heart failure. Ralinepag extended-release (XR), is a once-daily oral prostacyclin (IP) receptor to treat PAH. This study evaluated the safety, tolerability, and pharmacokinetics (PK) of multiple ascending doses of ralinepag XR tablets in fed and fasted healthy adult volunteers.</p><h3>Study Design and Methods</h3><p>A single-center, open-label, nonrandomized, multiple-dose titration study of two cohorts (fed (<i>n</i> = 13) or fasted (<i>n</i> = 15)) with once-daily dosing of ralinepag XR for 5 days, with up to four sequential dose escalations. Dosing began at 60 µg and escalated every 5 days as tolerated (120, 180, 240, and 300 µg). Doses were administered after a 10-h overnight fast or a moderate-fat breakfast. PK parameters assessed were maximum observed concentration (<i>C</i>_max), area under the concentration–time curve from time 0 to 24 h postdose (AUC_(0–24)), and time of maximum observed concentration (<i>T</i>_max) on day 1 (single 60 μg dose); and C_max, AUC_(0–24), and T_max at steady state.</p><h3>Results</h3><p>Ralinepag XR exhibited minimal differences in PK parameters between fed and fasted states in the first 24 h. Multiple-dose administration showed a dose-dependent increase in exposure and a median 4–10 h <i>T</i>_max at steady state, independent of fed status. Ralinepag accumulation was approximately 2.1-fold after 5 days of dosing at 60 μg in both fed and fasted states, consistent with a mean half-life of 20–36 h. There were no serious adverse events attributable to ralinepag. The most commonly reported adverse events were headache, jaw pain, and nausea with no differences between groups.</p><h3>Conclusions</h3><p>Food status did not significantly affect the PK or safety of ralinepag XR.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"26 5","pages":"621 - 630"},"PeriodicalIF":3.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40256-026-00807-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Artificial Intelligence to Identify Patterns and Predictors of Adverse Drug Reactions in Cardiovascular Patients: A Comprehensive Narrative Review","authors":"Erfan Shahabinejad,&nbsp;Fatemeh Soflaei-Shahrbabak,&nbsp;Marzieh Gholami Shoa,&nbsp;Aida Azhdarimoghaddam,&nbsp;Mehrdad Mozafar,&nbsp;Pouya Yektaee-Rad,&nbsp;Samar Monajemi,&nbsp;Shayan Ghanouni,&nbsp;Shuhao Qiu,&nbsp;Mani Khorsand Askari","doi":"10.1007/s40256-026-00810-y","DOIUrl":"10.1007/s40256-026-00810-y","url":null,"abstract":"<div><p>Artificial intelligence (AI) has emerged as a transformative tool for improving the detection, prediction, and prevention of adverse drug reactions (ADRs) in cardiovascular (CV) medicine, a domain characterized by high drug utilization, complex multimorbidity, and substantial polypharmacy. Traditional pharmacovigilance (PV) systems, particularly spontaneous reporting, remain limited by underreporting, variable data quality, and delayed signal recognition, underscoring the need for computationally enhanced approaches. This narrative review synthesizes current evidence on AI applications across the cardiovascular PV continuum, including safety signal detection, patient-level risk prediction, and text-based surveillance. Machine learning (ML) models, applied to structured datasets such as the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), VigiBase, and electronic health records (EHRs), and curated drug–target databases have shown improved discriminatory performance compared with conventional approaches in identifying bleeding risk under direct oral anticoagulants, predicting acute kidney injury in patients with heart failure, and estimating susceptibility to drug-induced QT prolongation, primarily in internal validation settings. Natural language processing (NLP) advances, particularly transformer-based models, further facilitate extraction of drug–event relationships from clinical notes and patient-generated content. Despite these advances, major challenges persist, including data heterogeneity, selective reporting biases, mechanistic ambiguity in CV ADRs, and limited external validation. Ethical considerations, including privacy preservation, algorithmic transparency, bias mitigation, and human oversight, remain critical for responsible implementation. Looking forward, the integration of real-time biosignal streams from wearable devices, multimodal multiomics data, and explainable AI frameworks may further refine individualized risk assessment and facilitate earlier detection of cardiotoxic events in appropriately validated settings. Collectively, AI holds substantial promise for enhancing cardiovascular drug safety, provided its deployment is accompanied by rigorous validation, robust governance, and alignment with clinical workflows.</p></div>","PeriodicalId":7652,"journal":{"name":"American Journal of Cardiovascular Drugs","volume":"26 5","pages":"537 - 557"},"PeriodicalIF":3.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468395","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":"Combination Therapy of GLP-1 RA and SGLT2i in Patients with Established Heart Failure: A Systematic Review and Meta-Analysis of Observational Studies","authors":"Christopher Daniel Tristan,&nbsp;Irnizarifka Irnizarifka,&nbsp;Erlangga Masykur Kynaya,&nbsp;Mellisa Gani,&nbsp;Matthew Aldo Wijayanto,&nbsp;An Aldia Asrial,&nbsp;Raymond Pranata","doi":"10.1007/s40256-026-00812-w","DOIUrl":"10.1007/s40256-026-00812-w","url":null,"abstract":"<div><h3>Background</h3><p>A combination of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) and a Sodium-Glucose co-transporter-2 Inhibitor (SGLT2i) has demonstrated complementary benefits. This analysis aimed to compare combination therapy (GLP-1 RA and SGLT2i) with SGLT2i alone, both on top of standard HF care, in patients with baseline HF.</p><h3>Methods</h3><p>Systematic searches (PubMed, ScienceDirect, Scopus) and citation searching were performed on February 17, 2026. Original studies directly compared combination therapy and SGLT2i alone in patients with pre-existing HF diagnosis were included. Primary endpoints were all-cause mortality, all-cause hospitalization, and worsening heart failure (WHF). NOS was used for quality assessment. R (v.4.4.1) was used for random-effect meta-analysis. Certainty of evidence was evaluated using the GRADE framework.</p><h3>Results</h3><p>Eight cohorts (<i>n</i> = 75,833 patients) were included. Combination therapy resulted in a lower risk of all-cause mortality [RR: 0.62; 95% CI: 0.47–0.83; <i>p</i> = 0.0014], all-cause hospitalization [RR: 0.89; 95% CI: 0.84–0.96; <i>p</i> = 0.0012], and WHF [RR: 0.74; 95% CI: 0.64–0.87; <i>p</i> = 0.0001] during 1-year follow-up. Combination therapy was associated with significantly improved LVEF [MD: 3.83%; 95% CI: 0.44–7.22; <i>p</i> = 0.0397] and reduced acute kidney injury risk [HR: 0.70; 95% CI: 0.65–0.74] without any significant increase in adverse events (including hypoglycemia, gastrointestinal side effects, pancreatitis, and urinary tract infections). GRADE assessment yielded moderate evidence for three primary endpoints.</p><h3>Conclusions</h3><p>In patients with established HF, combination of GLP-1 RA and SGLT2i therapy was associated with significant reductions in mortality, hospitalization, and WHF, without significant adverse events. Further randomized trials are urgently warranted to confirm such outcomes.</p><h3>Registration</h3><p>PROSPERO identifier no. CRD420261320840.</p><h3>Graphical abstract</h3>\u0000<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":"589 - 602"},"PeriodicalIF":3.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417991","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}