Tryvio (aprocitentan) / Idorsia - LARVOL DELTA

Endothelin Receptor Antagonists in Resistant Hypertension and Proteinuric Kidney Disease: Receptor Strategy and Volume Management. (PubMed, J Clin Hypertens (Greenwich)) - "Aprocitentan is the first and only ERA approved for hypertension; in PRECISION, the approved 12.5-mg once-daily dose reduced placebo-corrected 24-h ambulatory systolic blood pressure by 4.2 mm Hg, with reductions of 4.2 to 5.9 mm Hg across the studied doses. In IgA nephropathy (IgAN), sparsentan reduces proteinuria and slows estimated glomerular filtration rate (eGFR) decline. Atrasentan has an established antiproteinuric effect and a favorable eGFR slope, although the prespecified week-136 eGFR contrast in the final ALIGN analysis did not reach statistical significance. Zibotentan plus dapagliflozin remains investigational. Across these settings, successful ERA use depends on careful patient selection, indication-specific interpretation of the evidence, optimized diuretic and cardiorenal therapy, and early surveillance for edema, anemia, liver-test abnormalities, and pregnancy risk, with treatment interruption or discontinuation when clinically significant..."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Glomerulonephritis • Hematological Disorders • Hypertension • IgA Nephropathy • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases

Emerging Pharmacological Therapies for Hypertension. (PubMed, Curr Hypertens Rev) - "This review provides a general overview of the physiological effects and pharmacokinetic properties that affect the absorption, distribution, metabolism, and elimination of recently developed antihypertensive drugs, such as fimasartan, azilsartan, zilebesiran, aprocitentan, and esaxerenone. Mechanistic differences among these agents are also highlighted; for instance, fimasartan and azilsartan inhibit the angiotensin II receptor, whereas other medications alter mineralocorticoid activity or endothelial pathways. The review further discusses the clinical implications of these mechanisms in hypertension management and supports informed therapeutic decisionmaking by providing a detailed understanding of the pharmacological and mechanistic profiles of these emerging antihypertensive therapies."

Journal • Cardiovascular • Hypertension

Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system. (PubMed, Can J Physiol Pharmacol) - "Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ETA and ETB receptors in 1990, enabling rapid development of the first endothelin receptor antagonists (bosentan, ambrisentan, and macitentan) for pulmonary arterial hypertension, a condition marked by elevated ET-1. Nearly a decade later, a new therapeutic wave began with the ETB agonist sovateltide (2021) for cerebral ischemic stroke, demonstrating the benefits of ETB activation...Clazosentan (ETA) for cerebral vasospasm and aprocitentan (ETA/ETB) for resistant hypertension extended endothelin-targeted therapy into more common diseases. In kidney disease, sparsentan (AT1/ETA) and atrasentan (ETA) have both been approved for IgA nephropathy, with atrasentan succeeding after earlier failed trials...This review outlines approaches for identifying legacy endothelin compounds suitable for new indications, using zibotentan, now combined with dapagliflozin to reduce fluid retention as an example. Kidney..."

Journal • Review • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Ischemic stroke • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • EDN1

Effect of Fourth-Line Antihypertensive Therapy on Clinic Systolic Blood Pressure in Resistant Hypertension: A Systematic Review and Meta-Analysis. (PubMed, Blood Press) - "Pairwise comparisons against placebo showed that aldosterone targeted therapies produced the largest reductions in SBP, with lorundrostat (MD -11.70 mmHg [95% CI -16.07, -7.33]) and baxdrostat 2 mg (MD -10.10 [-12.63, -7.58]) showing comparable effects, while baxdrostat 1 mg (MD -8.56 [-11.08 to -6.04]) demonstrated reductions similar in magnitude to spironolactone (MD -7.95 [-10.10, -5.80]). β-blockers, including bisoprolol (MD = -6.71 mm Hg), also demonstrated modest SBP reductions, while aprocitentan 12.5 mg reduced SBP by -3.80 mmHg [-6.65, -0.95]...Significant increases in any adverse events were observed with aprocitentan 25 mg (RR 1.89 [1.39, 2.57]) and doxazosin (RR 1.55 [1.09, 2.20])...Due to transitivity violations across trials, indirect comparative rankings remain invalid. Future trials are required to establish efficacy and assess outcomes."

Journal • Retrospective data • Review • Cardiovascular • Hypertension

New Drugs on the Horizon for Hypertension. (PubMed, Adv Kidney Dis Health) - "This includes the nonselective endothelin receptor antagonist aprocitentan, which was Food and Drug Administration approved in 2024 for uncontrolled hypertension. Aldosterone synthase inhibitors including baxdrostat, lorundrostat, and vicadrostat are in phase 1 or 2 trials for hypertension or chronic kidney disease with evidence of significant blood pressure lowering. Finally, the novel small-interfering RNA-based zilebesiran targeting angiotensinogen represents a new class of antihypertensive medications with durable blood pressure-lowering dosing only every 3 or 6 months. Each of these medications has unique properties that can potentially contribute to improvement in blood pressure control for individual patients and at the population level. Development of these novel antihypertensives promises a welcome set of new options for the treatment of hypertension."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Baxdrostat (Baxfendy) - an aldosterone synthase inhibitor for hypertension. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Hypertension

A Study Evaluating Aprocitentan Tablets(SYH9108) for the Treatment of Resistant Hypertension (clinicaltrials.gov) - P3 | N=382 | Not yet recruiting | Sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

New P3 trial • Cardiovascular • Hypertension

Aprocitentan: An oral, once-daily antihypertensive therapy for resistant hypertension in adult patients. (PubMed, Heart Int) - P3 | "Pharmacokinetic studies support once-daily oral administration with low potential for drug-drug interactions. This article will discuss the significant potential benefits in the evolving landscape of hypertension management, how aprocitentan is a promising fourth-line agent for rHTN and recommendations for its use in the 2025 American Heart Association/American College of Cardiology (AHA/ACC) High Blood Pressure Guideline."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Hypertension • Inflammation • Nephrology • Renal Disease • EDN1

Aprocitentan: A New Option for Resistant Hypertension and Its Place in Patient Care. (PubMed, South Med J) - "The PRECISION clinical trial resulted in a mean change in office systolic blood pressure at 4 weeks of -15.3 mm Hg for aprocitentan 12.5 mg, -15.2 mm Hg for aprocitentan 25 mg, and -11.5 mm Hg for placebo, for a difference versus placebo of -3.8 mm Hg (97.5% confidence interval -6.8 to -0.8, P=0.0042) and -3.7 (1.3) mm Hg (97.5% confidence interval -6.7 to -0.8, P=0.0046), respectively. Aprocitentan has shown benifit in further reduction of blood pressure for individuals who have failed standard triple therapy, such as a combination of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, nondihydropyridine calcium channel blocker, and thiazide or thiazide."

Journal • Review • Cardiovascular • Hypertension

Aprocitentan in resistant hypertension with chronic kidney disease: balancing albuminuria reduction against early volume risk. (PubMed, J Hum Hypertens) - "We also discuss the physiological rationale for combining endothelin blockade with SGLT2 inhibitors as a potential strategy to improve the balance between efficacy and tolerability. Overall, aprocitentan should be interpreted within a clinical benefit-risk framework in which resistant hypertension is the primary therapeutic target, while albuminuria reduction and early volume surveillance define its potential role in CKD."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

Supramolecular host-guest interactions of TRYVIO and VAFSEO with a benzotriazole nanocapsule: A density functional theory study. (PubMed, J Mol Graph Model) - "The higher value of dipole moments of the complexes indicated their high polarity and improved solubility in the polar solvents. Overall, the findings establish the benzotriazole supramolecular nanocapsule as an effective therapeutic carrier of CKD therapeutics."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Overpowered by uncontrolled hypertension: can we win this war? (PubMed, J Hypertens) - "Precise root cause analysis of suboptimal blood pressure control remains critically important for development of most optimal management strategies. We suggest the following evidence-supported steps can be immediately undertaken to improve uncontrolled hypertension treatment outcomes: reduction of the Medicare Quality Payment Program set blood pressure target to widely accepted goal of less than 130/80 mmHg, with the intent of providing additional cardiovascular benefits for senior US citizens; improving hypertension awareness and utilization of ambulatory blood pressure monitoring tools, as well as more frequent screening of uncontrolled patients for treatment noncompliance and/or therapeutic inertia; use of newer pharmaceutical agents in treatment of refractory hypertension, such as recently approved-agent aprocitentan; polypill treatment strategy encouragement, intending to improve poor medication compliance in the areas with challenging socioeconomic conditions; and..."

Journal • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Coronary Artery Disease • Hypertension • Nephrology • Renal Disease

Resistant Hypertension: Pathophysiology, Diagnostic Approaches, and Emerging Therapeutic Strategies. (PubMed, Curr Hypertens Rev) - "Resistant hypertension represents a multifactorial condition requiring a multidimensional diagnostic and therapeutic approach. Integrating lifestyle changes, optimized pharmacotherapy, and emerging options, including aldosterone synthase inhibition, dual endothelin receptor antagonism, small-interfering RNA strategies, and refined device-based approaches, offers incremental BP reductions in carefully selected patients. The synthesis emphasizes a pragmatic, stepwise strategy that couples adherence and secondary cause assessment with evidence-based pharmacologic intensification (notably mineralocorticoid receptor antagonists) and selective device therapy. This integrated approach may be critical for achieving durable BP control and reducing cardiovascular risk in patients with resistant hypertension."

Journal • Cardiovascular • Chronic Kidney Disease • Endocrine Disorders • Hypertension • Nephrology • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Disorder

ARE EDEMA EVENTS IN PRECISION ASSOCIATED WITH AN INCREASED RISK OF HOSPITALIZATION FOR HEART FAILURE? (ACC 2026) - "As a result, some had to switch from loop diuretics or ≥1 diuretic to hydrochlorothiazide (HCTZ; 25 mg/d). HFH in pts receiving aprocitentan was rare and mainly occurred in pts with pre-existing HF and other comorbidities. The protocol-mandated switch to HCTZ from other diuretics most probably contributed to HFH. The incidence of edema events was similar in both HF and non-HF groups, but HFH was higher in the HF cohort, suggesting HFH was not primarily driven by edema observed in PRECISION."

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Obesity • Renal Disease

Macitentan vs Standard of Care in Pediatric Pulmonary Arterial Hypertension (TOMORROW): A Randomized Clinical Trial. (PubMed, J Pediatr) - "TOMORROW was a novel study assessing PK and the long-term efficacy and safety of macitentan vs SoC in pediatric PAH. The results confirm the adequacy of the macitentan dosing in this population and provided signals of potential benefit of macitentan over SoC for children with PAH."

Clinical • Journal • Cardiovascular • Hypertension • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Placental transfer of the novel endothelin-1 receptor antagonist aprocitentan. (PubMed, Pregnancy Hypertens) - "Aprocitentan transfers across the human placental barrier, although its fetal levels following maternal application of 150 ng/mL were insufficient to block endothelin-1. Drug studies in isolated cotyledons should consider the intervillous space when calculating recovery."

Journal • Cardiovascular • Gynecology • Hypertension • EDN1

Endothelin as a Treatment Target in Cardiovascular Diseases: A Recent Step Forward. (PubMed, Rev Cardiovasc Med) - "Recently, aprocitentan, an endothelin-1 inhibitor, was approved to treat arterial hypertension. Meanwhile, endothelin has become a therapeutic target in CVDs, with inhibitors previously registered and used to treat pulmonary hypertension. Thus, this review aims to comprehensively discuss the role of endothelin-1 as a therapeutic target in CVDs and related disorders."

Journal • Review • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • EDN1

A New Drug for Resistant Hypertension: Aprocitentan. (PubMed, Curr Hypertens Rev) - "Its mechanism of action, improved efficacy, and excellent tolerability make aprocitentan a promising therapeutic option for resistant hypertension. It may be particularly effective in the treatment of patients with comorbidities, such as diabetes and CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Diabetes • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • EDN1

Aprocitentan, an endothelin receptor antagonist for resistant hypertension. (PubMed, JAAPA) - "Although this new drug expands available options for RH, it requires careful patient selection and monitoring. Finally, cost and insurance coverage may limit access."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hypertension • Nephrology • Renal Disease

Revolutionizing resistant hypertension: Unlocking the potential of Aprocitentan. (PubMed, J Pak Med Assoc) - No abstract available

Journal • Cardiovascular • Hypertension

Aprocetentin (Tryvio): A breakthrough in treating Resistant Hypertension. (PubMed, J Pak Med Assoc) - No abstract available

Journal • Cardiovascular • Hypertension

Current Knowledge About Aprocitentan in Hypertension. (PubMed, Int J Mol Sci) - "Moreover, ACT was compatible with other antihypertensive agents, demonstrating synergistic or additive effects in some cases. Since HT is frequently associated with comorbidities and ACT targets a different pathway than the existing antihypertensive drugs, ACT may play a pivotal role in the management of resistant hypertension."

Journal • Review • Cardiovascular • Genetic Disorders • Hypertension • Obesity

Aprocitentan in Patients With Chronic Kidney Disease and Resistant Hypertension. (PubMed, Hypertension) - P3 | "Aprocitentan may confer considerable cardiovascular and kidney-protective benefits in these difficult-to-treat patients. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03541174."

Journal • Cardiovascular • Chronic Kidney Disease • Hypertension • Nephrology • Renal Disease

The antihypertensive agent ACT-132577 alleviates cuproptosis and pressure-overload-induced vascular remodelling by modulation of the NEDD4-LCTR1-copper signaling. (PubMed, FEBS J) - "More importantly, knocking down NEDD4L significantly abolished the effects of ACT-132577 on cuproptosis and VSMC phenotypic transition. In conclusion, ACT-132577 plays a crucial role in cuproptosis and aortic remodelling by modulation of the NEDD4L-CTR1-copper signaling, providing a novel perspective on its therapeutic potential in mitigating pressure overload-induced vascular remodelling."

Journal • Cardiovascular • Hypertension • Targeted Protein Degradation • ACTA2 • DLAT • MMP2 • MMP9 • NEDD4 • PDGFB • UBR5

The use of predictive, preventive, and personalized medical approaches to optimize hypertension management. (PubMed, EPMA J) - "The 3PM framework leverages AI-driven integration of multi-omics, retinal imaging like ViT models, and hemodynamic profiling for risk prediction and treatment response forecasting; genetic profiling such as MTHFR, UMOD variants, urinary proteomics (CKD273 classifier), and microbiome-guided nutrition for early intervention; and pharmacogenomics, digital phenotyping like smartphone-guided dosing, and novel therapies such as aprocitentan and finerenone for personalized efficacy. Specific findings include aprocitentan reducing systolic BP by -15.3 mmHg in resistant hypertension, UMOD-guided torasemide use lowering BP by 8.5 mmHg in carriers, and microbiome-based nutrition reducing systolic BP by 14% in hyperglycemic patients...3PM transforms hypertension management by enabling proactive, individualized care. However, rigorous validation, affordable diagnostics, pragmatic trials, and equitable access are essential to bridge translational gaps and..."

Journal • Review • Cardiovascular • Diabetes • Hypertension • MTHFR