Drugs最新文献

{"title":"Incretin-Based Anti-obesity Medications in Polycystic Ovary Syndrome: The Evidence Map.","authors":"Mojca Jensterle, Andrej Janez","doi":"10.1007/s40265-026-02325-x","DOIUrl":"https://doi.org/10.1007/s40265-026-02325-x","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common, heterogeneous condition that is tightly linked to obesity, visceral adiposity and insulin resistance. Lifestyle intervention and off-label use of metformin provide only modest and unsustained weight loss, insufficient to reverse obesity-driven pathophysiology in most women with PCOS and obesity. Incretin-based anti-obesity medications, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (dual GIP/GLP-1RAs), offer a biologically plausible way to target adipose dysfunction, hyperinsulinemia and chronic inflammation that drive PCOS in a large subset of patients. In this narrative, product-segmented review, we map the evidence for liraglutide, semaglutide and tirzepatide in PCOS across mechanistic, clinical, and safety domains, and highlight key evidence gaps that limit current practice. Liraglutide has the densest PCOS-specific evidence, demonstrating reproducible weight loss across small and heterogeneous cohorts, reductions in visceral adiposity and hepatic fat, improved glycemia and inflammatory markers, and early signals for androgen and fertility benefits in selected phenotypes. Semaglutide data remain sparse but conceptually rich, demonstrating weight-loss efficacy and mechanistic insights, alongside preliminary signals of increased likelihood of natural conception. Tirzepatide currently has no PCOS-specific evidence and cannot be recommended beyond extrapolation from obesity and diabetes trials. Across all agents, reproductive outcomes, periconceptional and pregnancy safety, adolescent use, long-term cardiovascular-kidney-metabolic trajectories, obstructive sleep apnea, musculoskeletal health and phenotype-stratified response remain major evidence gaps. We propose a multidimensional, metabolic high-risk PCOS phenotype as the most rational current target for incretin therapy, while emphasizing that well-designed, PCOS-specific trials are essential before these drugs can be viewed as PCOS-modifying therapies rather than powerful, but still adjunctive, weight-loss agents.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large Vessel Vasculitis: Recent Advances in Pathophysiology and Targeted Therapies.","authors":"Myriam Reisch, Jens Thiel, Philipp Bosch","doi":"10.1007/s40265-026-02323-z","DOIUrl":"https://doi.org/10.1007/s40265-026-02323-z","url":null,"abstract":"<p><p>Large vessel vasculitides (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK), share common features such as inflammation of large sized arteries but differ in several key aspects, including age of onset and pathogenic mechanism. This narrative review gives an update of recent insights into pathogenesis of GCA and TAK, and discusses emerging targeted therapies based on these insights. It highlights omics-based signatures, ULK3 and SLAMF7 in GCA, EGR1 in TAK, alongside genetic and somatic risk factors such as clonal haematopoiesis (DNMT3A/TET2) linked to relapse and ischaemic vision loss in GCA, and the IL6R-p.Asp358Ala variant as a predictor of reduced interleukin (IL)-6 receptor blockade response. Common mechanisms include CD4⁺ T-cell, monocyte/macrophage, and B-cell infiltration with activation of IL-6, JAK/STAT/interferon, and IL-17 pathways. Giant cell arteritis is characterised by GM-CSF-driven macrophages and disrupted programmed cell death (PD)-1/PD-L1 checkpoint regulation, while TAK shows dominance of CD8⁺ T cells and tumour necrosis factor (TNF)-α signalling. Interleukin-6 receptor inhibitors (e.g., tocilizumab) show robust efficacy in GCA but with notable non-responders; the JAK inhibitor upadacitinib demonstrated efficacy in a Phase III study, whereas IL-17 blockade (secukinumab) yielded inconsistent results. In TAK, TNF inhibitors and tocilizumab are comparably effective; early data suggest Janus kinases (JAK) inhibitors promote remission, imaging improvement, and glucocorticoid sparing. Mavrilimumab (GM-CSF receptor blockade) is promising in GCA. Recent studies have increasingly focused on short-term glucocorticoid therapy in combination with biologic agents. Advances in biomarker research, including investigation of the IL-6 receptor and IL-17A gene polymorphisms, may enable more targeted therapeutic strategies.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etripamil: First Approval.","authors":"Michael B Brown","doi":"10.1007/s40265-026-02321-1","DOIUrl":"https://doi.org/10.1007/s40265-026-02321-1","url":null,"abstract":"<p><p>Etripamil (CARDAMYST^TM) is an intranasal L-type calcium channel blocker (CCB) developed by Milestone Pharmaceuticals for the treatment of symptomatic paroxysmal supraventricular tachycardia (PSVT) and is under investigation for atrial fibrillation with rapid ventricular rate (AF-RVR). It received its first approval on the 12 December 2025 in the USA for the conversion of acute symptomatic PSVT episodes to sinus rhythm in adults. Additional global regulatory filings of etripamil for PSVT in adults, a phase II trial of etripamil in pediatrics, and a phase III trial for AF-RVR are in progress. This article summarizes the milestones in the development of etripamil leading to this first approval for PSVT.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Immune-Based Approaches for the Cure of HIV Infection.","authors":"Julia A Wagner, Demi A Sandel, Amelia N Deitchman, Rachel L Rutishauser, Steven G Deeks, Michael J Peluso","doi":"10.1007/s40265-026-02311-3","DOIUrl":"10.1007/s40265-026-02311-3","url":null,"abstract":"<p><p>Despite significant advances in antiretroviral therapy, the need for a cure for HIV persists because of factors such as long-term antiretroviral therapy-related comorbidities, disease stigma, and inequities in access to care. Most cure efforts focus on inducing durable HIV remission (antiretroviral therapy-free viral control) either by augmenting immune function or reducing the HIV reservoir. In this review, we highlight immune-based cure interventions currently under investigation with a particular focus on those that have demonstrated the ability to induce durable HIV remission after analytic treatment interruption, here termed \"post-intervention control\". While current cure interventions are generally complex, expensive, and not easily scalable, they provide critical \"proof of principle\" that a cure for HIV is possible. Continuing to make studies of HIV cure a funding priority is important, we believe, as continued optimization of cure interventions should eventually lead to a cure that is simple, safe, effective, affordable, and scalable. In addition, we highlight critical features in clinical trial design and pharmacokinetics/pharmacodynamics that should be considered prior to clinical trial implementation.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Anti-nerve Growth Factor Monoclonal Antibodies in Managing Chronic Musculoskeletal Pain: A Systematic Review with Network Meta-analysis.","authors":"Ahmed Abouelella, Qasi Najah, Richard O Day, Lars Arendt-Nielsen, Maria A Lopez-Olivo, Matthew K Bagg, K T Matthew Seah, Mohammad Alhasan, Ahmed Hamoudah, Ola Abuzied, Mansoor Al-Tamimi, Ayman Ibrahim, Eman Basheer, Reham Mahgoub, Muhammed Elhadi","doi":"10.1007/s40265-026-02304-2","DOIUrl":"10.1007/s40265-026-02304-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) have emerged as a promising new class of analgesics, offering potential benefits in managing particular painful musculoskeletal (MSK) conditions. However, their long-term safety remains uncertain, leading to regulatory non-approval of these agents. This study aims to evaluate the efficacy and safety of individual anti-NGF mAbs compared to other analgesics when treating chronic MSK pain.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Our literature search included PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov through April 25th, 2025. Articles eligible for inclusion were randomized controlled trials (RCTs) comparing one of the human anti-NGF mAbs to other interventions in adults with chronic MSK pain. Primary outcomes evaluated were changes from baseline in pain, physical function, and patient global assessment (PGA) scores, as well as risks of adjudicated arthropathies (AAs) and abnormal peripheral sensation (APS). We used the Cochrane Risk of Bias 2 (RoB-2) tool to assess risk of bias. Pairwise and network meta-analyses were performed using random-effects models. Treatments were ranked using the cumulative ranking curve (SUCRA), and a multi-criteria decision analysis with Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) was applied to integrate all efficacy and safety outcomes. Statistical analyses were conducted in R (v4.3.1) using the meta, netmeta, gemtc, and Multi-Criteria Decision Aiding (MCDA) packages.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 29 studies, involving 27,747 patients with osteoarthritis or chronic low back pain, were included in this analysis. Compared to placebo, fasinumab showed the highest improvements in pain (standardized mean difference [SMD] - 0.40, 95% CI [- 0.52, - 0.29], p &lt; 0.001) and physical function (SMD - 0.42, 95% CI [- 0.53, - 0.31], p &lt; 0.001), followed by tanezumab (pain: SMD - 0.36, 95% CI [- 0.44, - 0.28], p &lt; 0.001; function: SMD - 0.39, 95% CI [- 0.47, - 0.31], p &lt; 0.001). For safety, both fasinumab and tanezumab demonstrated a significant risk for AAs (risk ratio [RR] 4.7, 95% CI [3.61, 6.13], p &lt; 0.001; and RR 3.84, 95% CI [2.07, 7.14], p &lt; 0.001, respectively) and APS (RR 1.99, 95% CI [1.49, 2.65], p &lt; 0.001; and RR 2.46, 95% CI [1.93, 3.14], p &lt; 0.001, respectively) relative to placebo. While fulranumab was less effective (pain: SMD - 0.25, 95% CI [- 0.42, - 0.07], p &lt; 0.01; function: SMD - 0.25, 95% CI [- 0.43, - 0.07], p &lt; 0.01), it showed better overall safety against placebo relative to both agents, demonstrating a significant risk only for APS events (RR 1.78, 95% CI [1.09, 2.92], p &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Anti-NGF mAbs, particularly fasinumab and tanezumab, are associated with the greatest levels of pain relief and functional improvement over placebo within this analysis. However, these benefits are counterbalanced by significant risks of","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"719-736"},"PeriodicalIF":14.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sevabertinib: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40265-026-02299-w","DOIUrl":"10.1007/s40265-026-02299-w","url":null,"abstract":"<p><p>Sevabertinib (HYRNUO^®), an oral, reversible, small molecule tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptor 2 (HER2) that also shows activity against epidermal growth factor receptor (EGFR), is being developed by Bayer for the treatment of solid tumours with mutations in HER2 or EGFR genes. Sevabertinib is derived from Bayer's strategic research alliance with the Broad Institute of MIT and Harvard. In November 2025, sevabertinib was approved under accelerated approval in the USA for use in adults with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose tumours have HER2 (ERBB2) TK domain (TKD) activating mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This article summarizes the milestones in the development of sevabertinib leading to this first approval for the treatment of locally advanced or metastatic NSCLC with HER2 (ERBB2) activating mutations.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"759-764"},"PeriodicalIF":14.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sibeprenlimab: First Approval.","authors":"Arnold Lee","doi":"10.1007/s40265-026-02298-x","DOIUrl":"10.1007/s40265-026-02298-x","url":null,"abstract":"<p><p>Sibeprenlimab (VOYXACT^®; sibeprenlimab-szsi) is a fully humanized monoclonal antibody that binds to A PRoliferation Inducing Ligand (APRIL) being developed by Otsuka Pharmaceutical for the treatment of immunoglobulin A (IgA) nephropathy and Sjögren's disease. Signalling via APRIL is implicated in the inflammatory processes that ultimately result in damage to the glomeruli in patients with IgA nephropathy. Treatment with sibeprenlimab suppressed APRIL levels and reduced proteinuria in patients with IgA nephropathy, according to interim analyses from the ongoing VISIONARY phase III clinical trial. This article summarizes the milestones in the development of sibeprenlimab leading to this first approval to reduce proteinuria in adults with primary IgA nephropathy at risk for disease progression.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"765-768"},"PeriodicalIF":14.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plozasiran: First Approval.","authors":"Yahiya Y Syed","doi":"10.1007/s40265-026-02293-2","DOIUrl":"10.1007/s40265-026-02293-2","url":null,"abstract":"<p><p>Plozasiran (Redemplo^®) is a first-in-class GalNAc-conjugated small interfering RNA (siRNA) designed to reduce hepatic apolipoprotein C-III (ApoC3) production. It is being developed by Arrowhead Pharmaceuticals for the treatment of familial chylomicronemia syndrome (FCS), severe hypertriglyceridaemia and mixed hyperlipidaemia. Plozasiran degrades ApoC3 mRNA via RNA interference, reducing hepatic and serum ApoC3 levels and thereby enhancing catabolism and clearance of serum triglycerides. It received its first approval in the USA on 18 November 2025 as an adjunct to diet to reduce triglycerides in adults with FCS. This article summarizes the key milestones in the clinical development of plozasiran leading to its first approval for FCS.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"753-758"},"PeriodicalIF":14.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GOLD 2026: Transforming COPD Management with Early Intervention, Multi-dimensional Assessment, and Personalized Care.","authors":"Mario Cazzola, Jyoti Bajpai, Luigino Calzetta, Maria Gabriella Matera, Paola Rogliani","doi":"10.1007/s40265-026-02303-3","DOIUrl":"10.1007/s40265-026-02303-3","url":null,"abstract":"<p><p>The 2026 report from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) introduces substantial conceptual and practical updates to the management of chronic obstructive pulmonary disease. While maintaining the established spirometric definition, the report emphasizes early diagnosis, multi-dimensional assessment, and personalized treatment strategies that move beyond a spirometry-centric approach. Key innovations include formally recognizing disease activity as a therapeutic target, refining the ABE classification with a lower threshold for patients prone to exacerbations (Group E), and integrating blood eosinophil counts to guide inhaled corticosteroid therapy. Nonpharmacologic interventions, such as pulmonary rehabilitation, vaccination, smoking cessation, structured self-management, and post-exacerbation care, are elevated to core disease-modifying strategies. Pharmacological escalation is structured around dual bronchodilation as the preferred initial step, with further intensification to biomarker-guided triple therapy, including inhaled corticosteroids or other anti-inflammatory agents, reserved for selected patients who remain symptomatic or experience exacerbations despite optimized dual therapy. GOLD 2026 also introduces biologics, dupilumab and mepolizumab, as an add-on therapy for exacerbation-prone eosinophilic chronic obstructive pulmonary disease. However, it also highlights ongoing limitations in efficacy, cost effectiveness, and generalizability. Artificial intelligence and emerging digital technologies are recognized as promising adjuncts in the management of chronic obstructive pulmonary disease, though their clinical implementation remains preliminary. Overall, GOLD 2026 advances precision medicine in chronic obstructive pulmonary disease by combining structured individualized assessments with early targeted interventions. However, significant uncertainties remain, including biological variability of biomarkers, limited evidence for emerging therapies, and barriers to equitable access to nonpharmacologic and advanced interventions. Careful context-sensitive application and continued validation are essential.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"581-597"},"PeriodicalIF":14.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Renin Angiotensin Aldosterone System Inhibitors on Cardiovascular Outcomes in Hypertensive Population: A Network Meta-analysis of Randomized Controlled Trials.","authors":"Yueming Jiang, Jinbo Hu, Xiaoyan Yi, Qifu Li, Shumin Yang","doi":"10.1007/s40265-026-02302-4","DOIUrl":"10.1007/s40265-026-02302-4","url":null,"abstract":"<p><strong>Background: </strong>Renin-angiotensin-aldosterone system (RAAS) inhibitors are widely used for lowering blood pressure, but the optimal choice of RAAS inhibitors in reducing cardiovascular events remains unclear.</p><p><strong>Objectives: </strong>We aimed to compare the efficacy of RAAS inhibitors on cardiovascular outcomes in hypertensive population.</p><p><strong>Methods: </strong>A systematic literature search was performed in PubMed and the Central Cochrane Library. The primary efficacy outcome was major adverse cardiovascular events (MACE). Individual components of MACE including cardiovascular mortality, myocardial infarction, stroke, and heart failure were also analyzed. Network meta-analyses were conducted via a random-effects model within frequentist framework.</p><p><strong>Results: </strong>We analyzed 43 randomized controlled trials. Mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of MACE compared with placebo [risk ratio (RR) 0.82; 95% confidence interval (CI) 0.75-0.90] and were superior to angiotensin receptor blockers (ARBs; RR 0.87; 95% CI 0.78-0.99) and direct renin inhibitors (DRIs; RR 0.83; 95% CI 0.70-0.99). MRAs showed a nonsignificant trend toward benefit compared with angiotensin-converting enzyme inhibitors (ACEIs; RR 0.91; 95% CI 0.78-1.05). After excluding trials that specifically enrolled patients with heart failure, protective effect of MRAs was not significant, but suggested a trend toward benefit (RR 0.89; 95% CI 0.78-1.01). Subgroup analyses for diabetes and chronic kidney disease consistently showed significant MACE reduction with MRAs, regardless of whether patients had these comorbidities at baseline or not, while other RAAS inhibitors showed inconsistent results in the subgroup analysis. For individual events, MRAs showed higher efficacy in reducing cardiovascular mortality (RR 0.80; 95% CI 0.72-0.88) and heart failure (RR 0.83; 95% CI 0.70-0.98) compared with placebo, while ACEIs were more effective in reducing myocardial infarction (RR 0.65; 95% CI 0.51-0.82) and ARBs showed higher efficacy in reducing stroke (RR 0.88; 95% CI 0.80-0.98) compared with placebo.</p><p><strong>Conclusions: </strong>MRAs outperformed ARBs and DRIs in reducing MACE in patients with hypertension, with a nonsignificant trend toward benefit compared with ACEIs. This benefit was most pronounced in populations with heart failure and MRAs provided consistent cardiovascular protection across subgroups with diabetes or renal comorbidities. Given the current positioning of the guidelines, MRAs may merit earlier consideration in hypertension management, pending confirmatory outcome-driven randomized trials.</p><p><strong>Registration: </strong>PROSPERO identifier number CRD42023473004, registered on 28 October 2023.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"737-752"},"PeriodicalIF":14.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}