losartan and Aneurysm, Thoracic Aortic studies

Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
losartan : A biphenylyltetrazole where a 1,1'-biphenyl group is attached at the 5-position and has an additional trisubstituted imidazol-1-ylmethyl group at the 4'-position

Research Excerpts

Excerpt	Relevance	Reference
"The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan."	9.17	Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. ( Benson, DW; Bradley, TJ; De Backer, J; Dietz, HC; Forbus, GA; Gelb, BD; Guey, LT; Klein, GL; Lacro, RV; Lai, WW; Levine, JC; Lewin, MB; Loeys, BL; Mahony, L; Markham, LW; Paridon, SM; Pearson, GD; Pierpont, ME; Radojewski, E; Selamet Tierney, ES; Sharkey, AM; Wechsler, SB; Yetman, AT, 2013)
" This focused review emphasizes the results of clinical trials using β-blocker, losartan potassium, and irbesartan in patients with Marfan syndrome and comments briefly on mechanisms of aortic remodeling, including fibrosis and transforming growth factor β signaling."	9.01	Update on Clinical Trials of Losartan With and Without β-Blockers to Block Aneurysm Growth in Patients With Marfan Syndrome: A Review. ( Eagle, KA; Hofmann Bowman, MA; Milewicz, DM, 2019)
"There are indicators that losartan, a drug widely used to treat arterial hypertension in humans, offers the first potential for primary prevention of clinical manifestations in Marfan syndrome."	8.84	Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan? ( Cameron, DE; Carrel, T; Dietz, HC; Habashi, J; Matt, P; Van Eyk, JE, 2008)
"Losartan potassium (INN losartan), an antihypertensive drug, has been shown to prevent thoracic aortic aneurysm in Marfan syndrome through the inhibition of transforming growth factor beta."	7.76	Effectiveness of combination of losartan potassium and doxycycline versus single-drug treatments in the secondary prevention of thoracic aortic aneurysm in Marfan syndrome. ( Chum, E; Chung, AW; Kim, JM; van Breemen, C; Yang, HH, 2010)
"Losartan has been proposed as a new therapeutic tool for this purpose."	6.84	Efficacy of losartan as add-on therapy to prevent aortic growth and ventricular dysfunction in patients with Marfan syndrome: a randomized, double-blind clinical trial. ( Campens, L; De Backer, J; De Nobele, S; De Paepe, A; Devos, D; Muiño-Mosquera, L, 2017)
"Losartan has been proposed for the prevention of thoracic aortic aneurysm."	5.35	Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome. ( Chum, E; Chung, AW; Kim, JM; van Breemen, C; Yang, HH, 2009)
"The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan."	5.17	Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. ( Benson, DW; Bradley, TJ; De Backer, J; Dietz, HC; Forbus, GA; Gelb, BD; Guey, LT; Klein, GL; Lacro, RV; Lai, WW; Levine, JC; Lewin, MB; Loeys, BL; Mahony, L; Markham, LW; Paridon, SM; Pearson, GD; Pierpont, ME; Radojewski, E; Selamet Tierney, ES; Sharkey, AM; Wechsler, SB; Yetman, AT, 2013)
" This focused review emphasizes the results of clinical trials using β-blocker, losartan potassium, and irbesartan in patients with Marfan syndrome and comments briefly on mechanisms of aortic remodeling, including fibrosis and transforming growth factor β signaling."	5.01	Update on Clinical Trials of Losartan With and Without β-Blockers to Block Aneurysm Growth in Patients With Marfan Syndrome: A Review. ( Eagle, KA; Hofmann Bowman, MA; Milewicz, DM, 2019)
"There are indicators that losartan, a drug widely used to treat arterial hypertension in humans, offers the first potential for primary prevention of clinical manifestations in Marfan syndrome."	4.84	Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan? ( Cameron, DE; Carrel, T; Dietz, HC; Habashi, J; Matt, P; Van Eyk, JE, 2008)
"Losartan potassium (INN losartan), an antihypertensive drug, has been shown to prevent thoracic aortic aneurysm in Marfan syndrome through the inhibition of transforming growth factor beta."	3.76	Effectiveness of combination of losartan potassium and doxycycline versus single-drug treatments in the secondary prevention of thoracic aortic aneurysm in Marfan syndrome. ( Chum, E; Chung, AW; Kim, JM; van Breemen, C; Yang, HH, 2010)
"Losartan has been proposed as a new therapeutic tool for this purpose."	2.84	Efficacy of losartan as add-on therapy to prevent aortic growth and ventricular dysfunction in patients with Marfan syndrome: a randomized, double-blind clinical trial. ( Campens, L; De Backer, J; De Nobele, S; De Paepe, A; Devos, D; Muiño-Mosquera, L, 2017)
"Thoracic aortic aneurysm is a major health problem with multiple causes and potentially devastating consequences."	2.46	Is losartan the true panacea for aneurysm disease? CON. ( Danyi, P; Jovin, IS, 2010)
"Treatment with losartan significantly blocked TAC-induced vascular inflammation and macrophage accumulation."	1.39	Aortic remodeling after transverse aortic constriction in mice is attenuated with AT1 receptor blockade. ( Brasier, AR; Cao, JM; Geng, L; Guo, S; Kuang, SQ; Kwartler, CS; Milewicz, DM; Peters, AM; Prakash, SK; Villamizar, C, 2013)
"Losartan has been proposed for the prevention of thoracic aortic aneurysm."	1.35	Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome. ( Chum, E; Chung, AW; Kim, JM; van Breemen, C; Yang, HH, 2009)

Research

Studies (18)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Absolute Dimension

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	2 (11.11)	29.6817
2010's	13 (72.22)	24.3611
2020's	3 (16.67)	2.80

Authors	Studies
Sawada, H	1
Ohno-Urabe, S	1
Ye, D	1
Franklin, MK	1
Moorleghen, JJ	1
Howatt, DA	1
Mullick, AE	1
Daugherty, A	2
Lu, HS	1
Sun, Y	1
Asano, K	1
Sedes, L	1
Cantalupo, A	1
Hansen, J	1
Iyengar, R	1
Walsh, MJ	1
Ramirez, F	5
Muiño-Mosquera, L	1
De Nobele, S	1
Devos, D	1
Campens, L	1
De Paepe, A	1
De Backer, J	2
Lino Cardenas, CL	1
Kessinger, CW	1
MacDonald, C	1
Jassar, AS	1
Isselbacher, EM	1
Jaffer, FA	1
Lindsay, ME	1
Milewicz, DM	4
Dubacher, N	1
Münger, J	1
Gorosabel, MC	1
Crabb, J	1
Ksiazek, AA	1
Caspar, SM	1
Bakker, ENTP	1
van Bavel, E	1
Ziegler, U	1
Carrel, T	2
Steinmann, B	1
Zeisberger, S	1
Meienberg, J	1
Matyas, G	1
Hofmann Bowman, MA	1
Eagle, KA	1
Lacro, RV	1
Guey, LT	1
Dietz, HC	2
Pearson, GD	1
Yetman, AT	1
Gelb, BD	1
Loeys, BL	1
Benson, DW	1
Bradley, TJ	1
Forbus, GA	1
Klein, GL	1
Lai, WW	1
Levine, JC	1
Lewin, MB	1
Markham, LW	1
Paridon, SM	1
Pierpont, ME	1
Radojewski, E	1
Selamet Tierney, ES	1
Sharkey, AM	1
Wechsler, SB	1
Mahony, L	1
Liu, S	1
Xie, Z	1
Cassis, LA	1
Pearson, KJ	1
Gong, MC	1
Guo, Z	1
Kuang, SQ	1
Geng, L	1
Prakash, SK	2
Cao, JM	1
Guo, S	1
Villamizar, C	1
Kwartler, CS	1
Peters, AM	1
Brasier, AR	1
Cook, JR	1
Clayton, NP	1
Carta, L	1
Galatioto, J	1
Chiu, E	1
Smaldone, S	1
Nelson, CA	1
Cheng, SH	1
Wentworth, BM	1
Yang, HH	2
Kim, JM	2
Chum, E	2
van Breemen, C	2
Chung, AW	2
Danyi, P	1
Jovin, IS	1
Elefteriades, JA	1
Rifkin, DB	1
Matt, P	1
Habashi, J	1
Cameron, DE	1
Van Eyk, JE	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Trial of Beta Blocker Therapy (Atenolol) Versus Angiotensin II Receptor Blocker Therapy (Losartan) in Individuals With Marfan Syndrome (A Trial Conducted by the Pediatric Heart Network)[NCT00429364]	Phase 3	608 participants (Actual)	Interventional	2007-01-31	Completed
A Multicenter Randomized Controlled Trial of Exercise in Aortic Dissection Survivors[NCT05610462]		126 participants (Anticipated)	Interventional	2023-01-01	Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The rate of change in the absolute dimension of the aortic root over a 3-year period following randomization (NCT00429364)
Timeframe: Up to 3 years following randomization.

Annual Rate of Change in Aortic Root (Sinuses of Valsalva) Body-surface-area-adjusted Z-score

Intervention	cm/year (Least Squares Mean)
Atenolol	0.069
Losartan	0.075

The rate of aortic root enlargement, expressed as the annual change in the maximum aortic-root-diameter z score indexed to body-surface area over a 3-year period following randomization (NCT00429364)
Timeframe: Up to 3 years following randomization.

Annual Rate of Change in Aortic-annulus-diameter Z Score, Adjusted by Body-surface Area

Annual Rate of Change in Arm Span to Height Ratio

Annual Rate of Change in Ascending-aorta-diameter Z Score, Adjusted by Body-surface-area.

Annual Rate of Change in Body Mass Index

Annual Rate of Change in Body Mass Index for Age Z-score

Annual Rate of Change in Height

Annual Rate of Change in Height-for-age Z-score

Annual Rate of Change in the Absolute Diameter of the Aortic Annulus

Annual Rate of Change in the Absolute Diameter of the Ascending Aorta

Annual Rate of Change in Total Aortic Proximal Regurgitant Jet Area Indexed to Body-surface-area

Annual Rate of Change in Upper to Lower Segment Ratio

Annual Rate of Change in Weight

Annual Rate of Change in Weight-for-age Z-score

Annual Rate of Change in Weight-for-height Z-score

Event Rate of Aortic Dissection.

Intervention	z-score/year (Least Squares Mean)
Atenolol	-0.139
Losartan	-0.107

Intervention	z-score/year (Least Squares Mean)
Atenolol	-0.279
Losartan	-0.175

Intervention	1/year (Least Squares Mean)
Atenolol	0.001
Losartan	0.001

Intervention	z-score/year (Least Squares Mean)
Atenolol	-0.140
Losartan	-0.114

Intervention	kg/m^2 per year (Least Squares Mean)
Atenolol	0.063
Losartan	0.076

Intervention	z-score/year (Least Squares Mean)
Atenolol	0.007
Losartan	0.021

Intervention	cm/year (Least Squares Mean)
Atenolol	0.822
Losartan	0.935

Intervention	z-score/year (Least Squares Mean)
Atenolol	0.046
Losartan	0.019

Intervention	cm/year (Least Squares Mean)
Atenolol	0.015
Losartan	0.030

Intervention	cm/year (Least Squares Mean)
Atenolol	0.039
Losartan	0.044

Intervention	(mm^2/m^2)/year (Least Squares Mean)
Atenolol	0.005
Losartan	0.001

Intervention	1/year (Least Squares Mean)
Atenolol	-0.014
Losartan	-0.015

Intervention	kg/year (Least Squares Mean)
Atenolol	0.239
Losartan	0.229

Intervention	z-score/year (Least Squares Mean)
Atenolol	0.011
Losartan	0.019

Intervention	z-score/year (Least Squares Mean)
Atenolol	-0.001
Losartan	-0.157

Percentage of participants who had aortic dissection over a 3-year period following randomization. (NCT00429364)
Timeframe: Up to 3 years following randomization.

Event Rate of Aortic-Root Surgery

Intervention	Percentage of participants (Number)
Atenolol	0
Losartan	0.7

Percentage of participants who had aortic-root surgery over a 3-year period following randomization. (NCT00429364)
Timeframe: Up to 3 years following randomization.

Event Rate of Death

Intervention	Percentage of participants (Number)
Atenolol	3.4
Losartan	6.0

Percentage of participants who died over a 3-year period following randomization. (NCT00429364)
Timeframe: Up to 3 years following randomization.

Event Rate of the Composite Adverse Clinical Outcomes, Including Aortic Dissection, Aortic-root Surgery and Death.

Intervention	Percentage of participants (Number)
Atenolol	0
Losartan	0.3

Percentage of participants who had aortic dissection, aortic-root surgery or death over a 3-year period following randomization (NCT00429364)
Timeframe: Up to 3 years following randomization.

Intervention	participants (Number)
	Headache, any severity	Headache, bothersome	Fatigue, any severity	Fatigue, bothersome	Mood alterations, any severity	Mood alterations, bothersome	Behavior changes, any severity	Behavior changes, bothersome	Insomnia, any severity	Insomnia, bothersome	Nightmares, any severity	Nightmares, bothersome	Dizziness with standing, any severity	Dizziness with standing, bothersome	Dizziness - other, any severity	Dizziness - other, bothersome	Fainting with loss of consciousness, any severity	Fainting with loss of consciousness, bothersome	Palpitations, any severity	Palpitations, bothersome	Chest pain, any severity	Chest pain, bothersome	Dyspnea, any severity	Dyspnea, bothersome	Wheezing, any severity	Wheezing, bothersome	Upper respiratory/Nasal congestion, any severity	Upper respiratory/Nasal congestion, bothersome	Cough, any severity	Cough, bothersome	Dysgeusia, any severity	Dysgeusia, bothersome	Stomach pain/Indigestion, any severity	Stomach pain/Indigestion, bothersome	Nausea, any severity	Nausea, bothersome	Vomiting, any severity	Vomiting, bothersome	Diarrhea, any severity	Diarrhea, bothersome	Constipation, any severity	Constipation, bothersome	Vascular (hands, feet), any severity	Vascular (hands, feet), bothersome	Muscle pain or Cramps, any severity	Muscle pain or Cramps, bothersome	Back pain, any severity	Back pain, bothersome	Periorbital edema, any severity	Periorbital edema, bothersome	Pedal edema, any severity	Pedal edema, bothersome	Other, any severity	Other, bothersome
Atenolol	112	10	84	0	54	7	21	2	60	2	52	2	60	0	25	0	5	5	60	0	54	1	43	3	15	2	106	0	47	1	10	0	47	0	30	1	23	0	35	1	44	0	35	0	59	2	60	3	13	0	2	0	21	3
Losartan	114	10	105	0	49	3	23	1	61	2	53	3	58	2	27	1	9	9	53	0	58	5	38	0	14	1	117	2	59	0	3	0	61	1	35	0	23	0	43	1	35	0	34	1	58	4	67	2	15	0	3	0	16	1

Intervention	participants (Number)
	Headache, any severity	Headache, bothersome	Fatigue, any severity	Fatigue, bothersome	Mood alterations, any severity	Mood alterations, bothersome	Behavior changes, any severity	Behavior changes, bothersome	Insomnia, any severity	Insomnia, bothersome	Nightmares, any severity	Nightmares, bothersome	Dizziness with standing, any severity	Dizziness with standing, bothersome	Dizziness - other, any severity	Dizziness - other, bothersome	Fainting with loss of consciousness, any severity	Fainting with loss of consciousness, bothersome	Palpitations, any severity	Palpitations, bothersome	Chest pain, any severity	Chest pain, bothersome	Dyspnea, any severity	Dyspnea, bothersome	Wheezing, any severity	Wheezing, bothersome	Upper respiratory/Nasal congestion, any severity	Upper respiratory/Nasal congestion, bothersome	Cough, any severity	Cough, bothersome	Dysgeusia, any severity	Dysgeusia, bothersome	Stomach pain/Indigestion, any severity	Stomach pain/Indigestion, bothersome	Nausea, any severity	Nausea, bothersome	Vomiting, any severity	Vomiting, bothersome	Diarrhea, any severity	Diarrhea, bothersome	Constipation, any severity	Constipation, bothersome	Vascular (hands, feet), any severity	Vascular (hands, feet), bothersome	Muscle pain or Cramps, any severity	Muscle pain or Cramps, bothersome	Back pain, any severity	Back pain, bothersome	Periorbital edema, any severity	Periorbital edema, bothersome	Pedal edema, any severity	Pedal edema, bothersome	Other, any severity	Other, bothersome
Atenolol	202	27	152	7	89	13	51	5	108	6	100	7	119	6	60	2	21	21	86	0	114	14	75	1	36	2	188	3	117	1	29	0	119	2	99	0	81	1	94	1	77	1	73	0	148	6	137	5	22	0	6	0	105	10
Losartan	208	20	153	5	86	13	46	8	107	4	94	4	105	0	61	0	16	16	101	0	106	1	72	3	32	5	186	3	113	1	16	0	121	8	78	0	75	2	90	3	66	0	66	0	124	7	134	8	27	1	5	0	108	12

Article	Year
Therapies for Thoracic Aortic Aneurysms and Acute Aortic Dissections. Arteriosclerosis, thrombosis, and vascular biology, 2019, Volume: 39, Issue:2 Topics: Acute Disease; Angiotensin II; Animals; Aortic Aneurysm, Thoracic; Aortic Dissection; Humans; Losart	2019
Update on Clinical Trials of Losartan With and Without β-Blockers to Block Aneurysm Growth in Patients With Marfan Syndrome: A Review. JAMA cardiology, 2019, 07-01, Volume: 4, Issue:7 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Animals; Aortic Aneurysm, Thor	2019
Therapeutics Targeting Drivers of Thoracic Aortic Aneurysms and Acute Aortic Dissections: Insights from Predisposing Genes and Mouse Models. Annual review of medicine, 2017, 01-14, Volume: 68 Topics: Angiotensin II; Animals; Antihypertensive Agents; Aortic Aneurysm, Thoracic; Aortic Dissection; Dise	2017
Is losartan the true panacea for aneurysm disease? CON. Cardiology clinics, 2010, Volume: 28, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aortic Aneurysm, Thoracic; Disease Progression; Hu	2010
Recent advances in understanding Marfan syndrome: should we now treat surgical patients with losartan? The Journal of thoracic and cardiovascular surgery, 2008, Volume: 135, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aortic Aneurysm, Thoracic; Cohort Studies; Disease	2008

Article	Year
Efficacy of losartan as add-on therapy to prevent aortic growth and ventricular dysfunction in patients with Marfan syndrome: a randomized, double-blind clinical trial. Acta cardiologica, 2017, Volume: 72, Issue:6 Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Aortic Aneurysm, Thoracic; Double-Blind Method; Echo	2017
Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. American heart journal, 2013, Volume: 165, Issue:5 Topics: Adolescent; Adrenergic beta-1 Receptor Antagonists; Adult; Angiotensin II Type 1 Receptor Blockers;	2013

Article	Year
Inhibition of the Renin-Angiotensin System Fails to Suppress β-Aminopropionitrile-Induced Thoracic Aortopathy in Mice-Brief Report. Arteriosclerosis, thrombosis, and vascular biology, 2022, Volume: 42, Issue:10 Topics: Aminopropionitrile; Angiotensin II; Angiotensinogen; Animals; Aortic Aneurysm, Thoracic; Aortic Rupt	2022
Dissecting aortic aneurysm in Marfan syndrome is associated with losartan-sensitive transcriptomic modulation of aortic cells. JCI insight, 2023, 05-22, Volume: 8, Issue:10 Topics: Animals; Aorta; Aortic Aneurysm; Aortic Aneurysm, Thoracic; Aortic Dissection; Humans; Losartan; Mar	2023
Inhibition of the methyltranferase EZH2 improves aortic performance in experimental thoracic aortic aneurysm. JCI insight, 2018, 03-08, Volume: 3, Issue:5 Topics: Animals; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Disease Models, Animal; DNA Methylation; Enhanc	2018
Celiprolol but not losartan improves the biomechanical integrity of the aorta in a mouse model of vascular Ehlers-Danlos syndrome. Cardiovascular research, 2020, 02-01, Volume: 116, Issue:2 Topics: Adrenergic beta-1 Receptor Antagonists; Angiotensin II Type 1 Receptor Blockers; Animals; Aorta, Tho	2020
Mineralocorticoid receptor agonists induce mouse aortic aneurysm formation and rupture in the presence of high salt. Arteriosclerosis, thrombosis, and vascular biology, 2013, Volume: 33, Issue:7 Topics: Aldosterone; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Anim	2013
Aortic remodeling after transverse aortic constriction in mice is attenuated with AT1 receptor blockade. Arteriosclerosis, thrombosis, and vascular biology, 2013, Volume: 33, Issue:9 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Aorta; Aortic Aneurysm, T	2013
Dimorphic effects of transforming growth factor-β signaling during aortic aneurysm progression in mice suggest a combinatorial therapy for Marfan syndrome. Arteriosclerosis, thrombosis, and vascular biology, 2015, Volume: 35, Issue:4 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antibodies, Neutralizing; Aorta, Thoracic; Aortic	2015
Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome. British journal of pharmacology, 2009, Volume: 158, Issue:6 Topics: Age Factors; Angiotensin II Type 1 Receptor Blockers; Animals; Aorta, Thoracic; Aortic Aneurysm, Tho	2009
Effectiveness of combination of losartan potassium and doxycycline versus single-drug treatments in the secondary prevention of thoracic aortic aneurysm in Marfan syndrome. The Journal of thoracic and cardiovascular surgery, 2010, Volume: 140, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Diseas	2010
Editorial comment: losartan-based medical therapy for aneurysm disease. Cardiology clinics, 2010, Volume: 28, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aortic Aneurysm, Thoracic; Humans; Losartan; Treat	2010
Is losartan the drug for all seasons? Current opinion in pharmacology, 2012, Volume: 12, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Aortic Aneurysm, Thoracic	2012

losartan and Aneurysm, Thoracic Aortic