Tryvio (aprocitentan) / Idorsia - LARVOL DELTA

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

Aprocitentan in Resistant Hypertension: Mechanistic Insights, Clinical Evidence, and Future Directions. (PubMed, Zhongguo Ying Yong Sheng Li Xue Za Zhi) - "Aprocitentan could potentially prove useful in the future for vascular disease, heart failure, and diabetic nephropathy. Clarifying its potential role in the future to treat hypertension and cardiorenal disease will only be discernible through longer-term trials on cardiovascular endpoints and cost-effectiveness."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetic Nephropathy • Gastrointestinal Disorder • Heart Failure • Hypertension • Hypotension • Metabolic Disorders • Nephrology • Renal Disease

Is Aprocitentan's Effect on Albuminuria Merely Due to Lowered BP? Subgroup Analysis of the PRECISION Trial (KIDNEY WEEK 2025) - P3 | "The low correlation between change in SiSBP and change in UACR suggests that APRO’s effect on UACR is at least partly independent of its effect on blood pressure. Table: Placebo-corrected changes in SiSBP and UACR (baseline to Week 4) with aprocitentan 12.5 mg and 25 mg in subgroups with renal impairment"

Cardiovascular • Chronic Kidney Disease • Hypertension • Renal Disease

Which Veterans Cannot Resist Aprocitentan? (KIDNEY WEEK 2025) - "Aprocitentan is currently non-formulary at the VA, but these data suggest a significant proportion of veterans with hypertension would be candidates to have it prescribed. Eligibility criteria for Aprocitentan"

Acute Coronary Syndrome • Atrial Fibrillation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Diabetic Nephropathy • Heart Failure • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Effects of aprocitentan on prognostically relevant ambulatory blood pressure-derived variables in resistant hypertension. (PubMed, J Hypertens) - "In addition to a significant and sustained day and night-time ambulatory BP reduction, aprocitentan was associated with a higher proportion of patients experiencing dipping pattern normalization and more pronounced BP load reduction, indicating prognostic relevance. Increased arterial stiffness or salt sensitivity did not alter the BP response to aprocitentan, suggesting additional clinical benefit."

Journal • Cardiovascular • Hypertension

Clinical Evaluation of QTc Interval Prolongation With the Dual Endothelin Receptor Antagonist Aprocitentan. (PubMed, J Cardiovasc Pharmacol Ther) - "The predicted upper bound of the 2-sided 90% ΔΔQTcF confidence interval exceeded the 10 ms threshold of regulatory concern at 16.10 µg/mL, which was close to the geometric mean maximum concentration (ie, 16.77 µg/mL) obtained with a 100 mg supratherapeutic dose.ConclusionsAt the highest therapeutic dose of 25 mg, there was no clinically significant prolongation of QTc. The risk of QT prolongation with therapeutic doses of aprocitentan is considered low."

Clinical • Journal • Cardiovascular • Hypertension • Hypotension

In brief: Embryotoxicity REMS removal for endothelin receptor antagonists. (PubMed, Med Lett Drugs Ther) - No abstract available

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

Unveiling the Carbonic Anhydrase Inhibitory Profile of Aprocitentan: Kinetic and Structural Characterization. (PubMed, ACS Med Chem Lett) - "These findings highlight a previously unrecognized dual mechanism of action for aprocitentan involving not only endothelin receptor antagonism but also CA inhibition. The combined effect may enhance its antihypertensive efficacy and suggests new avenues for therapeutic exploration in resistant hypertension."

Journal • Cardiovascular • Hypertension

Aprocitentan: a new horizon in the treatment of hypertension. (PubMed, Expert Opin Pharmacother) - "However, a lack of long-term data necessitates future investigation regarding safety. Aprocitentan may represent a novel therapeutic alternative to treat patients with RH and CKD."

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

Structure-Property Relationships Reported for the New Drugs Approved in 2024. (PubMed, Mini Rev Med Chem) - "The analysis focused on aprocitentan, flurpiridaz F-18, inavolisib, vorasidenib, ensitrelvir, golidocitinib, and zorifertinib, highlighting the key structural modifications that enhanced their drug-like properties. When developing central nervous system-penetrant drugs such as zorifertinib, careful control of rotatable bonds, hydrogen bond donors, and molecular lipophilicity was critical for optimizing blood-brain barrier penetration while remaining suitable for oral administration. These findings on structureproperty relationships offer valuable guidance for future drug development, particularly in addressing challenges related to solubility, bioavailability, and tissue-specific drug distribution."

Journal

Aprocitentan: The First Endothelin Receptor Antagonist for Resistant Hypertension. (PubMed, Am J Ther) - "Aprocitentan is a novel endothelin receptor antagonist approved for the treatment of resistant hypertension. It is a welcome development in the arsenal to fight against resistant hypertension for those with difficulty to manage with conventionally available antihypertensive medications."

Clinical • Journal • Cardiovascular • Hypertension • UGT1A1

Endothelin antagonists for hypertension: has their time finally arrived? (PubMed, Clin Sci (Lond)) - "Following a successful trial in resistant hypertension, a novel antihypertensive agent has been approved in Europe and in the U.S.A.: the dual ETAR/ETBR antagonist aprocitentan, which was recently approved for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs. Thus, the time has finally arrived for ET antagonists in hypertension."

Journal • Review • Cardiovascular • Hypertension • Hypotension

Endothelin Receptor Antagonists for the Treatment of Hypertension: Recent Data from Clinical Trials and Implementation Approach. (PubMed, Curr Cardiol Rep) - "Aprocitentan was well tolerated and the risk of fluid retention can be mitigated by close clinical monitoring and titration of diuretic therapy. Aprocitentan presents a novel treatment option for resistant hypertension, with particular efficacy noted in patient cohorts who have historically been challenging to achieve blood pressure targets in."

Journal • Review • Cardiovascular • Diabetes • Hypertension • Metabolic Disorders • Renal Disease

Drug Interactions of Imperatorin and Curcumin on Macitentan in vitro and in vivo. (PubMed, Drug Des Devel Ther) - "The metabolite ACT-132577 exhibited substantial increases in t1/2, Tmax, and Cmax. Furthermore, molecular docking revealed that the metabolic inhibition of macitentan by imperatorin and curcumin occurred through binding to the site on CYP3A4. However, further investigation is necessary to ascertain whether this phenomenon will occur in humans."

Journal • Preclinical • CYP3A4