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F. Angeli, G. Reboldi, P. Verdecchia (2015)
Interpretation of ambulatory blood pressure profile: a prognostic approach for clinical practice.Journal of hypertension, 33 3
M. Weber, H. Black, G. Bakris, H. Krum, S. Linas, Robert Weiss, J. Linseman, B. Wiens, M. Warren, L. Lindholm (2009)
A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trialThe Lancet, 374
Rebecca Moore, S. Linas (2010)
Endothelin antagonists and resistant hypertension in chronic kidney diseaseCurrent Opinion in Nephrology and Hypertension, 19
P. Sidharta, J. Dingemanse (2019)
Effect of Multiple-Dose Aprocitentan Administration on the Pharmacokinetics of Midazolam in Healthy Male SubjectsEuropean Journal of Drug Metabolism and Pharmacokinetics, 45
E. Schiffrin (1998)
Endothelin and endothelin antagonists in hypertensionJournal of Hypertension, 16
EL Schiffrin (1995)
S5J Cardiovasc Pharmacol, 26
P. Sidharta, I. Ulč, J. Dingemanse (2019)
Single-Dose Pharmacokinetics and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Subjects with Severe Renal Function ImpairmentClinical Drug Investigation, 39
T. Attinà, R. Camidge, D. Newby, D. Webb (2005)
Endothelin antagonism in pulmonary hypertension, heart failure, and beyondHeart, 91
E. Schiffrin (1998)
Endothelin: role in hypertension.Biological research, 31 3
R. Haynes, M. Kastner, N. Wilczynski, et al. (2005)
Developing optimal search strategies for detecting clinically sound and relevant causation studies in EMBASEBMC Medical Informatics and Decision Making, 5
E. Schiffrin, R. Lariviere, Jin-S. Li, P. Sventek, R. Touyz (1995)
Enhanced Expression of Endothelin‐1 Gene May Cause Blood Pressure‐Independent Vascular HypertrophyJournal of Cardiovascular Pharmacology, 26
F. Ruschitzka, T. Quaschning, G. Noll, A. deGottardi, M. Rossier, F. Enseleit, D. Hürlimann, T. Lüscher, S. Shaw (2001)
Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11&bgr;-Hydroxysteroid Dehydrogenase Inhibition: Role of Nitric OxideCirculation: Journal of the American Heart Association, 103
G. Reboldi, F. Angeli, C. Cavallini, G. Gentile, G. Mancia, P. Verdecchia (2008)
Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of myocardial infarction, stroke and death: a meta-analysisJournal of Hypertension, 26
M. Iglarz, M. Clozel (2010)
At the heart of tissue: endothelin system and end-organ damage.Clinical science, 119 11
G. Bakris, L. Lindholm, H. Black, H. Krum, S. Linas, J. Linseman, S. Arterburn, P. Sager, M. Weber (2010)
Divergent Results Using Clinic and Ambulatory Blood Pressures: Report of a Darusentan-Resistant Hypertension TrialHypertension, 56
W. Elliott (2010)
A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled trialYearbook of Cardiology, 2010
E. Belaidi, M. Joyeux-faure, C. Ribuot, S. Launois, P. Lévy, D. Godin-Ribuot (2009)
Major role for hypoxia inducible factor-1 and the endothelin system in promoting myocardial infarction and hypertension in an animal model of obstructive sleep apnea.Journal of the American College of Cardiology, 53 15
H. Black, G. Bakris, M. Weber, Robert Weiss, M. Shahawy, R. Marple, G. Tannoury, S. Linas, B. Wiens, J. Linseman, R. Roden, M. Gerber (2007)
Efficacy and Safety of Darusentan in Patients With Resistant Hypertension: Results From a Randomized, Double‐Blind, Placebo‐Controlled Dose‐Ranging StudyThe Journal of Clinical Hypertension, 9
P. Verweij, P. Danaietash, B. Flamion, J. Ménard, M. Bellet (2020)
Randomized Dose-Response Study of the New Dual Endothelin Receptor Antagonist Aprocitentan in HypertensionHypertension (Dallas, Tex. : 1979), 75
J. Plojhar (1965)
[20 YEARS].Casopis lekaru ceskych, 104
Y. Rautureau, E. Schiffrin (2012)
Endothelin in hypertension: an updateCurrent Opinion in Nephrology and Hypertension, 21
P. Best, Charles McKenna, David Hasdai, David Holmes, A. Lerman (1999)
Chronic endothelin receptor antagonism preserves coronary endothelial function in experimental hypercholesterolemia.Circulation, 99 13
M. Barton, C. Haudenschild, L. d’Uscio, S. Shaw, K. Münter, T. Lüscher (1998)
Endothelin ETA receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice.Proceedings of the National Academy of Sciences of the United States of America, 95 24
F. Angeli, P. Verdecchia, C. Poltronieri, C. Bartolini, V. Filippo, C. D'Ambrosio, G. Reboldi (2014)
Ambulatory blood pressure monitoring in the elderly: features and perspectives.Nutrition, metabolism, and cardiovascular diseases : NMCD, 24 10
F. Angeli, P. Verdecchia, G. Reboldi, R. Gattobigio, M. Bentivoglio, J. Staessen, C. Porcellati (2004)
Calcium channel blockade to prevent stroke in hypertension: a meta-analysis of 13 studies with 103,793 subjects.American journal of hypertension, 17 9
P. Sidharta, J. Dingemanse (2020)
Effects of Multiple‐Dose Administration of Aprocitentan on the Pharmacokinetics of RosuvastatinClinical Pharmacology in Drug Development, 9
M. Yanagisawa, H. Kurihara, S. Kimura, Y. Tomobe, Mieko Kobayashi, Y. Mitsui, Y. Yazaki, K. Goto, T. Masaki (1988)
A novel potent vasoconstrictor peptide produced by vascular endothelial cellsNature, 332
E. Schiffrin, Richard Larivière, Jin-S. Li, P. Sventek (1996)
Enhanced expression of the endothelin-1 gene in blood vessels of DOCA-salt hypertensive rats: correlation with vascular structure.Journal of vascular research, 33 3
P. Sidharta, M. Melchior, M. Kankam, J. Dingemanse (2019)
Single- and multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual endothelin receptor antagonist aprocitentan in healthy adult and elderly subjectsDrug Design, Development and Therapy, 13
(2012)
retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist
E. Schiffrin, L. Deng, P. Sventek, R. Day (1997)
Enhanced expression of endothelin‐1 gene in resistance arteries in severe human essential hypertensionJournal of Hypertension, 15
Henry Krum, Reuven Viskoper, Yves Lacourcière, Michael Budde, Vincent Charlon (1998)
The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators.The New England journal of medicine, 338 12
(2007)
Efficacy and safety of darusentan in patients with resistant hypertension: results from a randomized, doubleblind, placebo-controlled dose-ranging study
M. Iglarz, C. Binkert, K. Morrison, W. Fischli, J. Gatfield, A. Treiber, T. Weller, M. Bolli, C. Boss, Stephan Buchmann, Bruno Capeleto, P. Hess, C. Qiu, M. Clozel (2008)
Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor AntagonistJournal of Pharmacology and Experimental Therapeutics, 327
F. Angeli, P. Verdecchia, G. Reboldi, R. Gattobigio, M. Bentivoglio, J. Staessen, C. Porcellati (2004)
Meta-Analysis of effectiveness or lack thereof of angiotensin-converting enzyme inhibitors for prevention of heart failure in patients with systemic hypertension.The American journal of cardiology, 93 2
EL Schiffrin (1998)
199Biol Res, 31
P. Verdecchia, F. Angeli, C. Cavallini, R. Gattobigio, G. Gentile, J. Staessen, G. Reboldi (2008)
Blood pressure reduction and renin-angiotensin system inhibition for prevention of congestive heart failure: a meta-analysis.European heart journal, 30 6
F. Amiri, A. Virdis, M. Neves, M. Iglarz, N. Seidah, R. Touyz, T. Reudelhuber, E. Schiffrin (2004)
Endothelium-Restricted Overexpression of Human Endothelin-1 Causes Vascular Remodeling and Endothelial DysfunctionCirculation, 110
G. Reboldi, G. Gentile, F. Angeli, G. Ambrosio, G. Mancia, P. Verdecchia (2011)
Effects of intensive blood pressure reduction on myocardial infarction and stroke in diabetes: a meta-analysis in 73 913 patientsJournal of Hypertension, 29
P. Ferrari (2002)
Endothelin 1 type a receptor antagonism prevents vascular dysfunction and hypertension induced by 11beta-hydroxysteroid dehydrogenase inhibition: role of nitric oxide.Circulation, 105 17
A. Sharifi, E. Schiffrin (1996)
Endothelin receptors mediating vasoconstriction in rat pressurized small arteries.Canadian journal of physiology and pharmacology, 74 8
(2004)
Metaanalysis of effectiveness or lack thereof of angiotensin-converting enzyme inhibitors for prevention of heart failure in patients with systemic hypertension
F. Angeli, G. Reboldi, C. Poltronieri, C. Bartolini, C. D'Ambrosio, V. Filippo, P. Verdecchia (2014)
Clinical utility of ambulatory blood pressure monitoring in the management of hypertensionExpert Review of Cardiovascular Therapy, 12
J. Bauersachs, D. Fraccarollo, P. Galuppo, Julian Widder, Georg Ertl (2000)
Endothelin-receptor blockade improves endothelial vasomotor dysfunction in heart failure.Cardiovascular research, 47 1
D. Kohan, D. Pollock (2012)
Endothelin antagonists for diabetic and non‐diabetic chronic kidney diseaseBritish Journal of Clinical Pharmacology, 76
M. Edwards (2004)
TrialThe Lancet, 364
Carmine Cardillo, C. Kilcoyne, M. Waclawiw, Richard Cannon, J. Panza (1999)
Role of endothelin in the increased vascular tone of patients with essential hypertension.Hypertension, 33 2
S. Sen, Shali Chen, B. Feng, M. Iglarz, S. Chakrabarti (2012)
Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist.Life sciences, 91 13-14
(2004)
Endotheliumrestricted overexpression of human endothelin-1 causes vascular remodeling and endothelial dysfunction
Role of endothelin - 1 in clinical
F. Trensz, Céline Bortolamiol, Markus Kramberg, Daniel Wanner, Hakim Hadana, Markus Rey, D. Strasser, S. Delahaye, P. Hess, E. Vezzali, U. Mentzel, J. Ménard, M. Clozel, M. Iglarz (2019)
Pharmacological Characterization of Aprocitentan, a Dual Endothelin Receptor Antagonist, Alone and in Combination with Blockers of the Renin Angiotensin System, in Two Models of Experimental HypertensionThe Journal of Pharmacology and Experimental Therapeutics, 368
F. Angeli, G. Gentile, M. Trapasso, P. Verdecchia, G. Reboldi (2018)
Role and prognostic value of individual ambulatory blood pressure components in chronic kidney diseaseJournal of Human Hypertension, 32
N. Dhaun, J. Goddard, D. Kohan, D. Pollock, E. Schiffrin, D. Webb (2008)
Role of endothelin-1 in clinical hypertension: 20 years on.Hypertension, 52 3
Rebecca Moorhouse, D. Webb, D. Kluth, N. Dhaun (2013)
Endothelin Antagonism and Its Role in the Treatment of HypertensionCurrent Hypertension Reports, 15
S. Ergul, David Parish, David Puett, Adviye Ergul (1996)
Racial differences in plasma endothelin-1 concentrations in individuals with essential hypertension.Hypertension, 28 4
M. Fontes, J. Dingemanse, P. Sidharta (2020)
Multiple‐Dose Pharmacokinetics, Safety, and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Healthy Japanese and Caucasian SubjectsClinical Pharmacology in Drug Development, 10
Pierre Mussy, P. Sidharta, G. Wuerzner, M. Maillard, N. Guérard, M. Iglarz, B. Flamion, J. Dingemanse, M. Burnier (2020)
Effects of the Dual Endothelin Receptor Antagonist Aprocitentan on Body Weight and Fluid Homeostasis in Healthy Subjects on a High Sodium DietClinical Pharmacology and Therapeutics, 109
(2021)
features and perspectives
L. McAuley, B. Pham, P. Tugwell, D. Moher (2000)
Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses?The Lancet, 356
Aprocitentan (ACT-132577) is an orally active, dual endothelin-1 (ET-1) receptor antagonist that prevents the binding of ET-1 to both ETA/ETB receptors. It is an active metabolite of macitentan (obtained by oxidative depropylation), an orphan drug used for the treatment of pulmonary arterial hypertension. Aprocitentan is highly bound to plasma proteins and is eliminated in both urine and feces. It is well tolerated across all doses (up to 600 mg with single dose and 100 mg once a day at multiple doses). Its pharmacokinetic profile shows a half-life of 44 h, fitting a once-daily dosing regimen with plasma ET-1 concentrations (reflecting ET receptor antagonism), significantly increasing with doses ≥ 25 mg. Only minor differences in exposure between healthy females and males, healthy elderly and adult subjects, fed and fasted conditions, and renal function have been observed. Aprocitentan in patients with resistant hypertension is currently under investigation in the PRECISION phase III trial (ClinicalTrials identifier: NCT03541174). Nonetheless, results of pre-clinical data and studies in humans support the potential role of aprocitentan in this clinical setting. The absolute blood pressure (BP) reductions with aprocitentan are in the ranges established as a surrogate for reduction in cardiovascular morbidity in hypertension. Significant changes in BP with aprocitentan are observed within 14 days, and its BP-lowering effects have also been documented with ambulatory BP monitoring. Finally, aprocitentan enhances the BP-lowering effects of other antihypertensive drugs, including renin-angiotensin-system blockers. In conclusion, aprocitentan ameliorates the effects of ET-1 and could potentially reduce BP and provide broader cardiovascular protection in patients with resistant hypertension. Available data support the hypothesis that this new agent could expand our antihypertensive arsenal in resistant hypertension, making aprocitentan an attractive candidate for further large-scale trials.
Cardiology and Therapy – Springer Journals
Published: Dec 1, 2021
Keywords: Aprocitentan; Endothelin; Resistant hypertension; Blood pressure; Treatment; Efficacy and safety
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