losartan and Marfan Syndrome 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

Marfan Syndrome: An autosomal dominant disorder of CONNECTIVE TISSUE with abnormal features in the heart, the eye, and the skeleton. Cardiovascular manifestations include MITRAL VALVE PROLAPSE, dilation of the AORTA, and aortic dissection. Other features include lens displacement (ectopia lentis), disproportioned long limbs and enlarged DURA MATER (dural ectasia). Marfan syndrome (type 1) is associated with mutations in the gene encoding FIBRILLIN-1 (FBN1), a major element of extracellular microfibrils of connective tissue. Mutations in the gene encoding TYPE II TGF-BETA RECEPTOR (TGFBR2) are associated with Marfan syndrome type 2.

Research Excerpts

Excerpt	Relevance	Reference
"The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS)."	9.34	Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial. ( Balm, R; de Waard, V; Groenink, M; Indrakusuma, R; Jalalzadeh, H; Mulder, BJM; Scholte, AJ; Timmermans, J; van Andel, MM; van den Berg, MP; Zwinderman, AH, 2020)
"In this exploratory study, ADRB1-rs1801253 was associated with atenolol response in children and young adults with Marfan syndrome."	9.34	Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome. ( Dietz, HC; Forbus, GA; Gelb, BD; Goldmuntz, E; Hoskoppal, A; James, J; Lacro, RV; Lee, TM; Levine, JC; Li, JS; Loeys, BL; Markham, LW; Meester, JAN; Mital, S; Morris, SA; Mosley, JD; Olson, AK; Renard, M; Roden, DM; Shaffer, CM; Sharkey, A; Sleeper, LA; Van Driest, SL; Young, L, 2020)
"Long-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups."	9.27	Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome. ( Evangelista, A; Forteza, A; García-Dorado, D; González Mirelis, J; Gutiérrez, L; Ibáñez, B; Rodríguez-Palomares, J; Sánchez, V; Teixido-Tura, G, 2018)
" atenolol in aortic dilation progression in Marfan syndrome (MFS) patients."	9.22	Efficacy of losartan vs. atenolol for the prevention of aortic dilation in Marfan syndrome: a randomized clinical trial. ( Centeno, J; Cortina, J; Evangelista, A; Ferreira-González, I; Forteza, A; García-Dorado, D; Gracia, T; Gutiérrez, L; Rodríguez-Palomares, J; Rufilanchas, JJ; Sánchez, V; Sanz, P; Teixidó-Turà, G, 2016)
"It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome."	9.20	Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome. ( de Waard, V; den Hartog, AW; Franken, R; Groenink, M; Maugeri, A; Meijers-Heijboer, HE; Micha, D; Mulder, BJ; Pals, G; Radonic, T; Scholte, AJ; Timmermans, J; van den Berg, MP; van Dijk, FS; Zwinderman, AH, 2015)
"We conducted a randomized, double-blind trial of losartan (100 mg QD) versus atenolol (50 mg QD) for 6 months in adults with Marfan syndrome."	9.20	Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome. ( Bhatt, AB; Buck, JS; Creager, MA; Gauvreau, K; Kadivar, S; Milian, J; Singh, MN; Zuflacht, JP, 2015)
"In this multicentre, open-label, randomized controlled trial with blinded assessments, we compared losartan treatment with no additional treatment in operated and unoperated adults with Marfan syndrome."	9.17	Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial. ( de Waard, V; den Hartog, AW; Franken, R; Groenink, M; Marquering, HA; Mulder, BJ; Radonic, T; Scholte, AJ; Spijkerboer, AM; Timmermans, J; van den Berg, MP; Zwinderman, AH, 2013)
"Since 2008, when angiotensin II type I receptor blockade with losartan was introduced in the prevention of cardiovascular manifestation of Marfan syndrome (MFS), a specific treatment to address the cardiovascular lesions became available."	9.17	Usefulness of losartan on the size of the ascending aorta in an unselected cohort of children, adolescents, and young adults with Marfan syndrome. ( Debrauwer, V; Hagl, M; Laccone, F; Michel-Behnke, I; Moser, E; Pees, C, 2013)
"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)
"To assess the tolerability and efficacy of the investigational use of the angiotensin II receptor blocker losartan added to β-blockade (BB) to prevent progressive aortic root dilation in patients with Marfan syndrome (MFS)."	9.17	Losartan added to β-blockade therapy for aortic root dilation in Marfan syndrome: a randomized, open-label pilot study. ( Chen, CA; Chiu, HH; Chiu, SN; Hu, FC; Lin, MT; Lu, CW; Wang, JK; Wu, MH, 2013)
" Preclinical models of Marfan syndrome showed promising results for losartan as a potential therapy to attenuate aortic dilation in mice."	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)
"Despite the retrospective design of the study and the small sample size, a beneficial effect of losartan therapy was observed in pediatric patients with Marfan syndrome in the mid and long term."	7.81	[Aortic root dilatation rate in pediatric patients with Marfan syndrome treated with losartan]. ( Angeli, E; Bonvicini, M; Donti, A; Gargiulo, GD; Guidarini, M; Lovato, L; Mariucci, E; Picchio, FM; Wischmeijer, A, 2015)
"A case of severe early-onset Marfan syndrome (MFS) led us to ask the question: 'Should an ARB, particularly losartan [intervention], compared with beta blockade alone [comparison], be commenced in all paediatric MFS patients [patient] with aortic root dilatation [outcome]?' The current literature was critically appraised to address this question."	7.81	Losartan therapy for cardiac disease in paediatricMarfan syndrome. ( Adès, L; Ewans, LJ; Roberts, P, 2015)
"Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown."	7.77	Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. ( Aziz, H; Bedja, D; Chen, Y; Dietz, HC; Doyle, JJ; Habashi, JP; Holm, TM; Judge, DP; Modiri, AN; Schoenhoff, F, 2011)
"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)
"Marfan syndrome is an inherited disease of the connective tissue."	6.76	[Study of the efficacy and safety of losartan versus atenolol for aortic dilation in patients with Marfan syndrome]. ( Centeno, J; Cortina, J; Evangelista, A; Forteza, A; García, D; García-Dorado, D; Gutiérrez, L; Rodríguez-Palomares, J; Sánchez, V; Sanz, P; Teixidó, G, 2011)
"Treatment with losartan will be compared with no additional treatment after 3 years of follow-up."	6.75	Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial. ( Baars, MJ; de Witte, P; Groenink, M; Mulder, BJ; Radonic, T; Zwinderman, AH, 2010)
"Reduced bone mineral density (osteopenia) is a poorly characterized manifestation of pediatric and adult patients afflicted with Marfan syndrome (MFS), a multisystem disorder caused by structural or quantitative defects in fibrillin-1 that perturb tissue integrity and TGFβ bioavailability."	5.36	Differential effects of alendronate and losartan therapy on osteopenia and aortic aneurysm in mice with severe Marfan syndrome. ( Carta, L; Cook, JR; Dietz, HC; Lee-Arteaga, S; Nistala, H; Ramirez, F; Rifkin, AN; Rifkin, DB; Siciliano, G; Smaldone, S, 2010)
"During development of thoracic aortic aneurysms in a mouse model of Marfan syndrome, upregulation of matrix metalloproteinase (MMP)-2 and -9 was accompanied by compromised aortic constriction and endothelium-dependent relaxation."	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 COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS)."	5.34	Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial. ( Balm, R; de Waard, V; Groenink, M; Indrakusuma, R; Jalalzadeh, H; Mulder, BJM; Scholte, AJ; Timmermans, J; van Andel, MM; van den Berg, MP; Zwinderman, AH, 2020)
"In this exploratory study, ADRB1-rs1801253 was associated with atenolol response in children and young adults with Marfan syndrome."	5.34	Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome. ( Dietz, HC; Forbus, GA; Gelb, BD; Goldmuntz, E; Hoskoppal, A; James, J; Lacro, RV; Lee, TM; Levine, JC; Li, JS; Loeys, BL; Markham, LW; Meester, JAN; Mital, S; Morris, SA; Mosley, JD; Olson, AK; Renard, M; Roden, DM; Shaffer, CM; Sharkey, A; Sleeper, LA; Van Driest, SL; Young, L, 2020)
"The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes."	5.27	Influence of Aortic Stiffness on Aortic-Root Growth Rate and Outcome in Patients With the Marfan Syndrome. ( Bradley, TJ; Campbell, MJ; Chen, S; Cohen, MS; Colan, SD; De Backer, J; Heydarian, H; Hoskoppal, A; Lacro, RV; Lai, WW; Levine, JC; Liou, A; Marcus, E; Nutting, A; Olson, AK; Parra, DA; Pearson, GD; Pierpont, ME; Printz, BF; Pyeritz, RE; Ravekes, W; Roman, MJ; Selamet Tierney, ES; Sharkey, AM; Sleeper, LA; Srivastava, S; Young, L, 2018)
"Long-term outcome of Marfan syndrome patients randomly assigned to losartan or atenolol showed no differences in aortic dilation rate or presence of clinical events between treatment groups."	5.27	Losartan Versus Atenolol for Prevention of Aortic Dilation in Patients With Marfan Syndrome. ( Evangelista, A; Forteza, A; García-Dorado, D; González Mirelis, J; Gutiérrez, L; Ibáñez, B; Rodríguez-Palomares, J; Sánchez, V; Teixido-Tura, G, 2018)
"The optimal dose of angiotensin receptor blocker is not known, and no data are available about losartan pharmacogenetic profile in Marfan syndrome; we have proposed a strategy to tackle this issue based on evaluating the major genetic polymorphisms involved in the losartan conversion into active carboxylic acid metabolite."	5.22	Pharmacogenetic approach to losartan in Marfan patients: a starting point to improve dosing regimen? ( Cheli, S; Clementi, E; Falvella, FS; Ferrara, A; Marelli, S; Montanelli, S; Pini, A; Salvi, L; Trifirò, G; Viecca, F, 2016)
" atenolol in aortic dilation progression in Marfan syndrome (MFS) patients."	5.22	Efficacy of losartan vs. atenolol for the prevention of aortic dilation in Marfan syndrome: a randomized clinical trial. ( Centeno, J; Cortina, J; Evangelista, A; Ferreira-González, I; Forteza, A; García-Dorado, D; Gracia, T; Gutiérrez, L; Rodríguez-Palomares, J; Rufilanchas, JJ; Sánchez, V; Sanz, P; Teixidó-Turà, G, 2016)
"It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome."	5.20	Beneficial Outcome of Losartan Therapy Depends on Type of FBN1 Mutation in Marfan Syndrome. ( de Waard, V; den Hartog, AW; Franken, R; Groenink, M; Maugeri, A; Meijers-Heijboer, HE; Micha, D; Mulder, BJ; Pals, G; Radonic, T; Scholte, AJ; Timmermans, J; van den Berg, MP; van Dijk, FS; Zwinderman, AH, 2015)
"We conducted a randomized, double-blind trial of losartan (100 mg QD) versus atenolol (50 mg QD) for 6 months in adults with Marfan syndrome."	5.20	Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome. ( Bhatt, AB; Buck, JS; Creager, MA; Gauvreau, K; Kadivar, S; Milian, J; Singh, MN; Zuflacht, JP, 2015)
"To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS)."	5.20	Marfan Sartan: a randomized, double-blind, placebo-controlled trial. ( Aegerter, P; Arnoult, F; Attias, D; Barthelet, M; Basquin, A; Boileau, C; Collignon, P; Delorme, G; Detaint, D; Dulac, Y; Dupuis-Girod, S; Edouard, T; Faivre, L; Habib, G; Jondeau, G; Milleron, O; Naudion, S; Odent, S; Pangaud, N; Plauchu, H; Ropers, J; Sassolas, F; Thomas-Chabaneix, J; Tubach, F; Wolf, JE, 2015)
"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)
"Since 2008, when angiotensin II type I receptor blockade with losartan was introduced in the prevention of cardiovascular manifestation of Marfan syndrome (MFS), a specific treatment to address the cardiovascular lesions became available."	5.17	Usefulness of losartan on the size of the ascending aorta in an unselected cohort of children, adolescents, and young adults with Marfan syndrome. ( Debrauwer, V; Hagl, M; Laccone, F; Michel-Behnke, I; Moser, E; Pees, C, 2013)
"To assess the tolerability and efficacy of the investigational use of the angiotensin II receptor blocker losartan added to β-blockade (BB) to prevent progressive aortic root dilation in patients with Marfan syndrome (MFS)."	5.17	Losartan added to β-blockade therapy for aortic root dilation in Marfan syndrome: a randomized, open-label pilot study. ( Chen, CA; Chiu, HH; Chiu, SN; Hu, FC; Lin, MT; Lu, CW; Wang, JK; Wu, MH, 2013)
"In this multicentre, open-label, randomized controlled trial with blinded assessments, we compared losartan treatment with no additional treatment in operated and unoperated adults with Marfan syndrome."	5.17	Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial. ( de Waard, V; den Hartog, AW; Franken, R; Groenink, M; Marquering, HA; Mulder, BJ; Radonic, T; Scholte, AJ; Spijkerboer, AM; Timmermans, J; van den Berg, MP; Zwinderman, AH, 2013)
"To demonstrate a beneficial effect of losartan on aortic dilatation when added to optimal therapy in patients with Marfan syndrome."	5.14	Rationale and design of a randomized clinical trial (Marfan Sartan) of angiotensin II receptor blocker therapy versus placebo in individuals with Marfan syndrome. ( Aegerter, P; Arnoult, F; Boileau, C; Bouffard, C; Collignon, P; Delrue, MA; Detaint, D; Dulac, Y; Faivre, LO; Gautier, M; Hoffman, I; Jondeau, G; Odent, S; Plauchu, H; Tchitchinadze, M; Tubach, F, 2010)
" Preclinical models of Marfan syndrome showed promising results for losartan as a potential therapy to attenuate aortic dilation in mice."	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)
" In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation."	4.93	Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys-Dietz Syndromes. ( Akazawa, H; Fujita, D; Fujiwara, T; Hara, H; Harada, M; Inuzuka, R; Komuro, I; Nawata, K; Takeda, N; Taniguchi, Y; Toko, H; Yagi, H, 2016)
"The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years."	4.89	Echocardiographic methods, quality review, and measurement accuracy in a randomized multicenter clinical trial of Marfan syndrome. ( Bradley, TJ; Campbell, MJ; Chen, S; Cohen, MS; Colan, SD; De Backer, J; Guey, LT; Heydarian, H; Lacro, RV; Lai, WW; Levine, JC; Lewin, MB; Marcus, E; Mart, CR; Pearson, GD; Pignatelli, RH; Printz, BF; Selamet Tierney, ES; Sharkey, AM; Shirali, GS; Sleeper, LA; Srivastava, S, 2013)
"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)
"The Pediatric Heart Network Marfan Trial was a randomized trial comparing atenolol versus losartan on aortic root dilation in 608 children and young adults with Marfan syndrome."	3.96	Recruitment, retention, and adherence in a clinical trial: The Pediatric Heart Network's Marfan Trial experience. ( Atz, AM; Cappella, E; Cnota, JF; Dagincourt, N; De Nobele, S; Grima, J; Hamstra, MS; Hollenbeck-Pringle, D; King, M; Korsin, R; Lacro, RV; Lambert, LM; MacCarrick, G; MacNeal, MK; Markham, LW; Pemberton, VL; Sylvester, DM; Trachtenberg, FL; Walter, P; Xu, M, 2020)
"This study confirms that angiotensin II type 1 receptor antagonism (losartan) decreases aortic aneurysm growth in a mouse model of MFS."	3.88	The Effect of a Nonpeptide Angiotensin II Type 2 Receptor Agonist, Compound 21, on Aortic Aneurysm Growth in a Mouse Model of Marfan Syndrome. ( Clijsters, M; Herijgers, P; Meuris, B; Schepens, J; Verbrugghe, P; Verhoeven, J; Vervoort, D, 2018)
"Despite the retrospective design of the study and the small sample size, a beneficial effect of losartan therapy was observed in pediatric patients with Marfan syndrome in the mid and long term."	3.81	[Aortic root dilatation rate in pediatric patients with Marfan syndrome treated with losartan]. ( Angeli, E; Bonvicini, M; Donti, A; Gargiulo, GD; Guidarini, M; Lovato, L; Mariucci, E; Picchio, FM; Wischmeijer, A, 2015)
"A case of severe early-onset Marfan syndrome (MFS) led us to ask the question: 'Should an ARB, particularly losartan [intervention], compared with beta blockade alone [comparison], be commenced in all paediatric MFS patients [patient] with aortic root dilatation [outcome]?' The current literature was critically appraised to address this question."	3.81	Losartan therapy for cardiac disease in paediatricMarfan syndrome. ( Adès, L; Ewans, LJ; Roberts, P, 2015)
" Currently, the most promising therapeutic drug in Marfan syndrome is losartan, by blocking the angiotensin II receptor type 1 and thereby inhibiting pSmad2 signaling."	3.80	No beneficial effect of general and specific anti-inflammatory therapies on aortic dilatation in Marfan mice. ( de Vries, CJ; de Waard, V; den Hartog, AW; Franken, R; Groenink, M; Hibender, S; Mulder, BJ; Radonic, T; Zwinderman, AH, 2014)
"Angiotensin II (AngII) mediates progression of aortic aneurysm, but the relative contribution of its type 1 (AT1) and type 2 (AT2) receptors remains unknown."	3.77	Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. ( Aziz, H; Bedja, D; Chen, Y; Dietz, HC; Doyle, JJ; Habashi, JP; Holm, TM; Judge, DP; Modiri, AN; Schoenhoff, F, 2011)
"Statins are similar to losartan in attenuating aortic root dilation in a mouse model of Marfan syndrome."	3.77	Pravastatin reduces Marfan aortic dilation. ( Black, A; Byrne, J; Dietz, HC; Hill, AD; Huuskonen, V; Kay, E; Kearney, S; McAllister, H; McGuinness, J; McLoughlin, D; Redmond, JM; Terzo, E, 2011)
"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)
"Losartan is an angiotensin II (Ang II) type I receptor (AT1R) antagonist proposed to have an antiplatelet activity via the inhibition of both the thromboxane A2 (TXA2) receptor (TP) and the glycoprotein VI (GPVI)."	2.80	Inhibition of Glycoprotein VI Clustering by Collagen as a Mechanism of Inhibiting Collagen-Induced Platelet Responses: The Example of Losartan. ( Jandrot-Perrus, M; Jiang, P; Jondeau, G; Loyau, S; Ropers, J; Tchitchinadze, M, 2015)
"Marfan syndrome is an inherited disease of the connective tissue."	2.76	[Study of the efficacy and safety of losartan versus atenolol for aortic dilation in patients with Marfan syndrome]. ( Centeno, J; Cortina, J; Evangelista, A; Forteza, A; García, D; García-Dorado, D; Gutiérrez, L; Rodríguez-Palomares, J; Sánchez, V; Sanz, P; Teixidó, G, 2011)
"Treatment with losartan will be compared with no additional treatment after 3 years of follow-up."	2.75	Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial. ( Baars, MJ; de Witte, P; Groenink, M; Mulder, BJ; Radonic, T; Zwinderman, AH, 2010)
" We present the analysis of our single-center Marfan children and adolescents cohort to assess the influence of age, sex, degree of cardiovascular involvement and dosage on losartan effectivity."	1.72	Initial Angiotensin Receptor Blocker Response in Young Marfan Patients Decreases After 3 Years of Treatment. ( Heno, J; Michel-Behnke, I; Pees, C, 2022)
"The contribution of arrhythmias is unclear."	1.48	Frequency of Ventricular Arrhythmias and Other Rhythm Abnormalities in Children and Young Adults With the Marfan Syndrome. ( Crosson, JE; Czosek, RJ; Lacro, RV; Love, BA; Mah, DY; McCrindle, BW; Muiño-Mosquera, L; Olson, AK; Pilcher, TA; Shah, MJ; Sleeper, LA; Tierney, ESS; Wechsler, SB; Young, LT, 2018)
"Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes."	1.40	Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome. ( Bénard, L; Carta, L; Chemaly, ER; Chiu, E; Cook, JR; Costa, KD; Hajjar, RJ; Hampton, TG; Ramirez, F; Rao, SK; Yurchenco, P, 2014)
"Losartan has been shown to prevent aneurysms in another mouse model of MFS, Fbn1(C1039G/+), through inhibition of the Erk1/2 pathway."	1.38	MMP-2 regulates Erk1/2 phosphorylation and aortic dilatation in Marfan syndrome. ( Baxter, BT; Knispel, R; Meisinger, T; Worth, JM; Xiong, W, 2012)
"Reduced bone mineral density (osteopenia) is a poorly characterized manifestation of pediatric and adult patients afflicted with Marfan syndrome (MFS), a multisystem disorder caused by structural or quantitative defects in fibrillin-1 that perturb tissue integrity and TGFβ bioavailability."	1.36	Differential effects of alendronate and losartan therapy on osteopenia and aortic aneurysm in mice with severe Marfan syndrome. ( Carta, L; Cook, JR; Dietz, HC; Lee-Arteaga, S; Nistala, H; Ramirez, F; Rifkin, AN; Rifkin, DB; Siciliano, G; Smaldone, S, 2010)
"Marfan's syndrome is a genetic disorder affecting connective tissues, and it can lead to death due to aortic defects if left untreated."	1.35	Targeting TGF-beta and the extracellular matrix in Marfan's syndrome. ( Han, Y; Kalluri, R, 2008)
"Losartan-treated Fbn1(C1039G/+) mice had lower total TGF-beta1 concentrations compared with age-matched Fbn1(C1039G/+) mice treated with placebo (P=0."	1.35	Circulating transforming growth factor-beta in Marfan syndrome. ( Carlson, OD; De Backer, J; Dietz, HC; Fu, Q; Griswold, BF; Habashi, J; Holm, T; Huso, DL; Loch, D; Loeys, B; Matt, P; McDonnell, NB; Schoenhoff, F; Van Erp, C; Van Eyk, JE, 2009)
"During development of thoracic aortic aneurysms in a mouse model of Marfan syndrome, upregulation of matrix metalloproteinase (MMP)-2 and -9 was accompanied by compromised aortic constriction and endothelium-dependent relaxation."	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)
"Losartan is an emerging therapy that may help slow down the rate of arterial dilatation."	1.35	Loeys-Dietz syndrome: a Marfan-like syndrome associated with aggressive vasculopathy. ( Choo, JT; Lai, AH; Tan, TH; Wong, KY, 2009)

Research

Studies (96)

Authors

Clinical Trials (9)

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	19 (19.79)	29.6817
2010's	62 (64.58)	24.3611
2020's	15 (15.63)	2.80

Authors	Studies
Pees, C	2
Heno, J	1
Michel-Behnke, I	2
Robertson, DM	1
Truong, DT	1
Cox, DA	1
Carmichael, HL	1
Ou, Z	1
Minich, LL	2
Williams, RV	1
Selamet Tierney, ES	5
Alonso, F	1
Li, L	2
Fremaux, I	1
Reinhardt, DP	2
Génot, E	1
Pedicino, D	3
Volpe, M	3
Sun, Y	1
Asano, K	1
Sedes, L	1
Cantalupo, A	1
Hansen, J	1
Iyengar, R	1
Walsh, MJ	1
Ramirez, F	9
Chen, KH	1
Chiu, HH	3
Kang, YN	2
van Andel, MM	1
Indrakusuma, R	1
Jalalzadeh, H	1
Balm, R	1
Timmermans, J	4
Scholte, AJ	4
van den Berg, MP	4
Zwinderman, AH	6
Mulder, BJM	1
de Waard, V	5
Groenink, M	6
Van Driest, SL	1
Sleeper, LA	5
Gelb, BD	3
Morris, SA	1
Dietz, HC	15
Forbus, GA	2
Goldmuntz, E	1
Hoskoppal, A	2
James, J	1
Lee, TM	1
Levine, JC	6
Li, JS	2
Loeys, BL	7
Markham, LW	5
Meester, JAN	1
Mital, S	1
Mosley, JD	1
Olson, AK	5
Renard, M	2
Shaffer, CM	1
Sharkey, A	1
Young, L	2
Lacro, RV	10
Roden, DM	1
Jondeau, G	4
Milleron, O	2
Boileau, C	3
Hamstra, MS	2
Pemberton, VL	3
Dagincourt, N	1
Hollenbeck-Pringle, D	2
Trachtenberg, FL	2
Cnota, JF	1
Atz, AM	2
Cappella, E	2
De Nobele, S	4
Grima, J	1
King, M	1
Korsin, R	2
Lambert, LM	1
MacNeal, MK	1
MacCarrick, G	1
Sylvester, DM	1
Walter, P	1
Xu, M	2
Ayers, R	1
Kelleman, M	1
Iannucci, G	1
McCracken, C	1
Oster, ME	1
Tehrani, AY	1
White, Z	1
Milad, N	2
Esfandiarei, M	2
Seidman, MA	2
Bernatchez, P	2
Souza, RB	1
Kawahara, EI	1
Farinha-Arcieri, LE	1
Gyuricza, IG	1
Neofiti-Papi, B	1
Miranda-Rodrigues, M	1
Teixeira, MBCG	1
Fernandes, GR	1
Lemes, RB	1
Gouveia, CH	1
Pereira, LV	1
Muiño-Mosquera, L	2
Devos, D	2
Campens, L	1
De Paepe, A	2
De Backer, J	8
Liu, LH	1
Lin, SM	1
Lin, DS	1
Chen, MR	1
Verbrugghe, P	1
Verhoeven, J	1
Clijsters, M	1
Vervoort, D	1
Schepens, J	1
Meuris, B	1
Herijgers, P	1
Sellers, SL	1
Chan, R	1
Mielnik, M	1
Jermilova, U	1
Huang, PL	1
de Crom, R	1
Hirota, JA	1
Hogg, JC	1
Sandor, GG	2
Van Breemen, C	4
Lino Cardenas, CL	1
Kessinger, CW	1
MacDonald, C	1
Jassar, AS	1
Isselbacher, EM	2
Jaffer, FA	1
Lindsay, ME	2
Roman, MJ	4
Bradley, TJ	6
Colan, SD	4
Chen, S	3
Campbell, MJ	2
Cohen, MS	2
Heydarian, H	2
Lai, WW	4
Liou, A	3
Marcus, E	2
Nutting, A	1
Parra, DA	1
Pearson, GD	5
Pierpont, ME	3
Printz, BF	3
Pyeritz, RE	5
Ravekes, W	1
Sharkey, AM	4
Srivastava, S	2
Mah, DY	1
Crosson, JE	1
Czosek, RJ	1
Love, BA	1
McCrindle, BW	1
Pilcher, TA	1
Tierney, ESS	1
Shah, MJ	1
Wechsler, SB	3
Young, LT	2
Teixido-Tura, G	2
Forteza, A	3
Rodríguez-Palomares, J	3
González Mirelis, J	1
Gutiérrez, L	3
Sánchez, V	3
Ibáñez, B	1
García-Dorado, D	3
Evangelista, A	3
Handisides, JC	1
Uzark, K	1
Atz, TW	1
Groh, GK	1
Lindauer, B	1
Neal, MKM	1
Morrison, T	1
Mussatto, KA	1
Pierpont, MEM	1
Radojewski, EA	1
Chi, SC	1
Wu, MH	2
Hofmann Bowman, MA	1
Eagle, KA	1
Milewicz, DM	2
Yamani, N	1
Al-Naimat, S	1
Khurshid, A	1
Usman, MS	1
Guey, LT	2
Lewin, MB	2
Mart, CR	1
Pignatelli, RH	1
Shirali, GS	1
Yetman, AT	2
Benson, DW	2
Klein, GL	3
Paridon, SM	3
Radojewski, E	3
Mahony, L	4
Laccone, F	1
Hagl, M	1
Debrauwer, V	1
Moser, E	1
Elshershari, H	1
Harris, C	1
Trindade, PT	1
den Hartog, AW	3
Franken, R	5
Radonic, T	4
Spijkerboer, AM	1
Marquering, HA	1
Mulder, BJ	6
Gutgesell, HP	1
Cook, JR	3
Carta, L	4
Bénard, L	1
Chemaly, ER	1
Chiu, E	2
Rao, SK	1
Hampton, TG	1
Yurchenco, P	1
Costa, KD	2
Hajjar, RJ	1
Hibender, S	1
de Vries, CJ	1
Bowen, JM	1
Connolly, HM	1
Braverman, AC	1
Grossfeld, PD	1
Stylianou, MP	2
Alghamdi, MH	1
Raffin, LA	1
Potts, MT	1
Williams, LD	1
Potts, JE	1
Kiess, M	1
Micha, D	1
Maugeri, A	1
van Dijk, FS	2
Meijers-Heijboer, HE	1
Pals, G	2
Clayton, NP	1
Galatioto, J	2
Smaldone, S	2
Nelson, CA	1
Cheng, SH	1
Wentworth, BM	1
Treasure, T	1
Pepper, J	1
Mohiaddin, R	1
Ziganshin, BA	1
Mukherjee, SK	1
Elefteriades, JA	1
Mallat, Z	1
Tedgui, A	1
Bhatt, AB	1
Buck, JS	1
Zuflacht, JP	1
Milian, J	1
Kadivar, S	1
Gauvreau, K	1
Singh, MN	1
Creager, MA	1
Arnoult, F	2
Ropers, J	2
Aegerter, P	2
Detaint, D	2
Delorme, G	1
Attias, D	1
Tubach, F	2
Dupuis-Girod, S	1
Plauchu, H	2
Barthelet, M	1
Sassolas, F	1
Pangaud, N	1
Naudion, S	1
Thomas-Chabaneix, J	1
Dulac, Y	2
Edouard, T	1
Wolf, JE	1
Faivre, L	1
Odent, S	2
Basquin, A	1
Habib, G	1
Collignon, P	2
El Morabit, A	1
Marquering, H	1
Planken, NR	1
Jiang, P	1
Loyau, S	1
Tchitchinadze, M	2
Jandrot-Perrus, M	1
Ewans, LJ	1
Roberts, P	1
Adès, L	1
Lengellé, C	1
Bejan-Angoulvant, T	1
Beau-Salinas, F	1
Jonville-Béra, AP	1
Sanz, P	2
Gracia, T	1
Centeno, J	2
Rufilanchas, JJ	1
Cortina, J	2
Ferreira-González, I	1
Mariucci, E	1
Guidarini, M	1
Donti, A	1
Lovato, L	1
Wischmeijer, A	1
Angeli, E	1
Gargiulo, GD	1
Picchio, FM	1
Bonvicini, M	1
O'Rourke, MF	1
Adji, A	1
Weber, T	1
Lee, JJ	1
Rao, S	1
Takeda, N	1
Yagi, H	1
Hara, H	1
Fujiwara, T	1
Fujita, D	1
Nawata, K	1
Inuzuka, R	1
Taniguchi, Y	1
Harada, M	1
Toko, H	1
Akazawa, H	1
Komuro, I	1
Gao, L	1
Chen, L	1
Fan, L	1
Gao, D	1
Liang, Z	1
Wang, R	1
Lu, W	1
Falvella, FS	1
Marelli, S	1
Cheli, S	1
Montanelli, S	1
Viecca, F	1
Salvi, L	1
Ferrara, A	1
Clementi, E	1
Trifirò, G	1
Pini, A	1
Prakash, SK	1
Brooke, BS	1
Habashi, JP	5
Judge, DP	5
Patel, N	1
Loeys, B	3
Kalluri, R	1
Han, Y	1
Jiménez, SA	1
Rosenbloom, J	1
Meijers-Heijboer, H	1
Robin, NH	1
Gambarin, FI	1
Favalli, V	1
Serio, A	1
Regazzi, M	1
Pasotti, M	1
Klersy, C	1
Dore, R	1
Mannarino, S	1
Viganò, M	1
Odero, A	1
Amato, S	1
Tavazzi, L	1
Arbustini, E	1
Matt, P	2
Schoenhoff, F	3
Habashi, J	2
Holm, T	1
Van Erp, C	3
Loch, D	1
Carlson, OD	1
Griswold, BF	1
Fu, Q	1
Huso, DL	2
McDonnell, NB	1
Van Eyk, JE	2
Yang, HH	2
Kim, JM	2
Chum, E	2
Chung, AW	2
Choo, JT	1
Tan, TH	1
Lai, AH	1
Wong, KY	1
de Witte, P	1
Baars, MJ	1
Gupta, A	1
Gaikwad, J	1
Khaira, A	1
Rana, DS	1
Hoffman, I	1
Faivre, LO	1
Delrue, MA	1
Bouffard, C	1
Gautier, M	1
Nistala, H	1
Lee-Arteaga, S	1
Siciliano, G	1
Rifkin, AN	1
Rifkin, DB	3
Möberg, K	1
Goetghebeur, E	1
Segers, P	1
Trachet, B	1
Vervaet, C	1
Coucke, P	1
Couzin-Frankel, J	1
Holm, TM	4
Doyle, JJ	2
Bedja, D	3
Chen, Y	2
Kim, D	1
Cohn, RD	3
Thomas, CJ	1
Patnaik, S	1
Marugan, JJ	1
Aziz, H	1
Modiri, AN	1
Teixidó, G	1
García, D	1
McLoughlin, D	1
McGuinness, J	1
Byrne, J	1
Terzo, E	1
Huuskonen, V	1
McAllister, H	1
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Wilson, DG	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
National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions[NCT01322165]		3,706 participants (Actual)	Observational	2007-11-30	Completed
A Randomized Double-blind Study Assessing the Effects of Losartan Versus Atenolol on Pulse Wave Velocity and the Biophysical Properties of the Aorta in Patients With Marfan Syndrome[NCT00593710]	Phase 2	17 participants (Actual)	Interventional	2008-01-31	Completed
Multicenter, Randomised, Double Blind Study of the Efficacy of Losartan on Aortic Dilatation in Patients With Marfan Syndrome[NCT00763893]	Phase 3	303 participants (Actual)	Interventional	2008-09-30	Terminated (stopped due to A similar publication has been released, suggesting a beneficial effect of sartans, and only 15 patients remained to be seen for their visit at 36 months.)
A Multicenter Randomized Controlled Trial of Exercise in Aortic Dissection Survivors[NCT05610462]		126 participants (Anticipated)	Interventional	2023-01-01	Active, not recruiting
Generation of Marfan Syndrome and Fontan Cardiovascular Models Using Patient-specific Induced Pluripotent Stem Cells[NCT02815072]		30 participants (Anticipated)	Observational	2013-10-31	Recruiting
Effects of Losartan vs. Nebivolol vs. the Association of Both on the Progression of Aortic Root Dilation in Marfan Syndrome (MFS) With FBN1 Gene Mutations.[NCT00683124]	Phase 3	291 participants (Anticipated)	Interventional	2008-07-31	Recruiting
Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve (BICATOR)[NCT02679261]	Phase 3	220 participants (Actual)	Interventional	2016-06-30	Completed
A Randomized, Open-label, Active Control Trial to Evaluate the Effect of LOSARTAN Therapy on the Progression of Aortic Root Dilation in Patients With Marfan Syndrome[NCT00651235]	Phase 2	44 participants (Anticipated)	Interventional	2007-02-28	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
Initial Angiotensin Receptor Blocker Response in Young Marfan Patients Decreases After 3 Years of Treatment. Pediatric cardiology, 2022, Volume: 43, Issue:3 Topics: Adolescent; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Child; Female	2022
Fibrillin-1 Regulates Arteriole Integrity in the Retina. Biomolecules, 2022, Sep-20, Volume: 12, Issue:10 Topics: Animals; Arterioles; Extracellular Matrix Proteins; Fibrillin-1; Fibrillins; Losartan; Marfan Syndro	2022
Protection and delay of aortic complications in the Marfan syndrome: a new indication for angiotensin receptor blockers on top of β blockers. European heart journal, 2023, Jan-21, Volume: 44, Issue:4 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonis	2023
Protection and delay of aortic complications in the Marfan syndrome: a new indication for angiotensin receptor blockers on top of β blockers. European heart journal, 2023, Jan-21, Volume: 44, Issue:4 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonis	2023
Protection and delay of aortic complications in the Marfan syndrome: a new indication for angiotensin receptor blockers on top of β blockers. European heart journal, 2023, Jan-21, Volume: 44, Issue:4 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonis	2023
Protection and delay of aortic complications in the Marfan syndrome: a new indication for angiotensin receptor blockers on top of β blockers. European heart journal, 2023, Jan-21, Volume: 44, Issue:4 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonis	2023
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
How do baseline aortic root diameter, age and fibrillin-1 mutation affect the pooled effect of losartan on aortic dilatation? European journal of preventive cardiology, 2020, Volume: 27, Issue:19 Topics: Dilatation; Fibrillin-1; Humans; Losartan; Marfan Syndrome; Mutation	2020
Marfan sartan saga, episode X. European heart journal, 2020, 11-14, Volume: 41, Issue:43 Topics: Angiotensin II Type 1 Receptor Blockers; Follow-Up Studies; Humans; Losartan; Marfan Syndrome; Trans	2020
Recruitment, retention, and adherence in a clinical trial: The Pediatric Heart Network's Marfan Trial experience. Clinical trials (London, England), 2020, Volume: 17, Issue:6 Topics: Adolescent; Anti-Arrhythmia Agents; Atenolol; Black or African American; Child; Child, Preschool; Cl	2020
Racial and ethnic differences in response to treatment for Marfan syndrome. Cardiology in the young, 2021, Volume: 31, Issue:12 Topics: Angiotensin II Type 1 Receptor Blockers; Aorta; Atenolol; Child; Humans; Losartan; Marfan Syndrome;	2021
Blood pressure-independent inhibition of Marfan aortic root widening by the angiotensin II receptor blocker valsartan. Physiological reports, 2021, Volume: 9, Issue:10 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aorta; Blood Pressure; Dose-Response Relationship,	2021
Hyperkyphosis is not dependent on bone mass and quality in the mouse model of Marfan syndrome. Bone, 2021, Volume: 152 Topics: Animals; Female; Fibrillin-1; Kyphosis; Losartan; Male; Marfan Syndrome; Mice; Transforming Growth F	2021
Losartan in combination with propranolol slows the aortic root dilatation in neonatal Marfan syndrome. Pediatrics and neonatology, 2018, Volume: 59, Issue:2 Topics: Drug Therapy, Combination; Fibrillin-1; Humans; Infant, Newborn; Losartan; Male; Marfan Syndrome; Mu	2018
The Effect of a Nonpeptide Angiotensin II Type 2 Receptor Agonist, Compound 21, on Aortic Aneurysm Growth in a Mouse Model of Marfan Syndrome. Journal of cardiovascular pharmacology, 2018, Volume: 71, Issue:4 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aorta; Aortic Aneurysm; Dilatation, Pathologic; Di	2018
Inhibition of Marfan Syndrome Aortic Root Dilation by Losartan: Role of Angiotensin II Receptor Type 1-Independent Activation of Endothelial Function. The American journal of pathology, 2018, Volume: 188, Issue:3 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Aortic Dissection; Blood	2018
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
Frequency of Ventricular Arrhythmias and Other Rhythm Abnormalities in Children and Young Adults With the Marfan Syndrome. The American journal of cardiology, 2018, 10-15, Volume: 122, Issue:8 Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Angiotensin II Type 1 Receptor Blockers; Arrhythmias	2018
Losartan for the Treatment of Marfan Syndrome: Hope Fades. Journal of the American College of Cardiology, 2018, 10-02, Volume: 72, Issue:14 Topics: Angiotensin II Type 1 Receptor Blockers; Atenolol; Dilatation; Humans; Losartan; Marfan Syndrome	2018
Paternal fibrillin-1 mutation transmitted to an affected son with neonatal marfan syndrome: the importance of early recognition. Cardiology in the young, 2014, Volume: 24, Issue:4 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Aorta; Dilatation, Pathologic;	2014
Losartan treatment in adult patients with Marfan syndrome: can we finally COMPARE? European heart journal, 2013, Volume: 34, Issue:45 Topics: Angiotensin II Type 1 Receptor Blockers; Aortic Diseases; Female; Humans; Losartan; Male; Marfan Syn	2013
Growth of the aorta in childhood. The American journal of cardiology, 2014, Feb-15, Volume: 113, Issue:4 Topics: Aorta, Thoracic; Female; Humans; Losartan; Male; Marfan Syndrome; Patient Selection; Ultrasonography	2014
Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome. The Journal of clinical investigation, 2014, Volume: 124, Issue:3 Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Animals; Cardiomyopathy, Dilated; Child; Cross-Secti	2014
No beneficial effect of general and specific anti-inflammatory therapies on aortic dilatation in Marfan mice. PloS one, 2014, Volume: 9, Issue:9 Topics: Animals; Anti-Inflammatory Agents; Aorta; Dilatation, Pathologic; Losartan; Marfan Syndrome; Mice; M	2014
Of Marfan's syndrome, mice, and medications. The New England journal of medicine, 2014, Nov-27, Volume: 371, Issue:22 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Aorta; Aortic Aneurysm; Atenol	2014
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
Atenolol versus Losartan in Marfan's Syndrome. The New England journal of medicine, 2015, 03-05, Volume: 372, Issue:10 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Aorta; Aortic Aneurysm; Atenol	2015
Atenolol versus Losartan in Marfan's Syndrome. The New England journal of medicine, 2015, 03-05, Volume: 372, Issue:10 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Aorta; Aortic Aneurysm; Atenol	2015
Atenolol versus Losartan in Marfan's Syndrome. The New England journal of medicine, 2015, 03-05, Volume: 372, Issue:10 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Aorta; Aortic Aneurysm; Atenol	2015
Atenolol versus Losartan in Marfan's Syndrome. The New England journal of medicine, 2015, 03-05, Volume: 372, Issue:10 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Aorta; Aortic Aneurysm; Atenol	2015
Potential Phenotype-Genotype Correlation in Marfan Syndrome: When Less is More? Circulation. Cardiovascular genetics, 2015, Volume: 8, Issue:2 Topics: Female; Genes, Dominant; Haploinsufficiency; Humans; Losartan; Male; Marfan Syndrome; Microfilament	2015
Marfan and Sartans: time to wake up! European heart journal, 2015, Aug-21, Volume: 36, Issue:32 Topics: Angiotensin II Type 1 Receptor Blockers; Aortic Diseases; Female; Humans; Losartan; Male; Marfan Syn	2015
Aortic disease: Losartan versus atenolol in the Marfan aorta-how to treat? Nature reviews. Cardiology, 2015, Volume: 12, Issue:8 Topics: Angiotensin II Type 1 Receptor Blockers; Aortic Diseases; Female; Humans; Losartan; Male; Marfan Syn	2015
Losartan therapy for cardiac disease in paediatricMarfan syndrome. Journal of paediatrics and child health, 2015, Volume: 51, Issue:9 Topics: Angiotensin II Type 1 Receptor Blockers; Aorta; Dilatation, Pathologic; Female; Heart Defects, Conge	2015
[Drugs news]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie, 2015, Volume: 22, Issue:11 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Anti-Obesity Agents; Anticonvu	2015
[Aortic root dilatation rate in pediatric patients with Marfan syndrome treated with losartan]. Giornale italiano di cardiologia (2006), 2015, Volume: 16, Issue:12 Topics: Adolescent; Angiotensin II Type 1 Receptor Blockers; Aortic Valve; Bicuspid Aortic Valve Disease; Ch	2015
Correspondence regarding: Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome by Bhatt et al. Vascular medicine (London, England), 2016, Volume: 21, Issue:1 Topics: Adrenergic beta-1 Receptor Antagonists; Angiotensin II Type 1 Receptor Blockers; Aortic Aneurysm; At	2016
Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome. Annals of biomedical engineering, 2016, Volume: 44, Issue:10 Topics: Animals; Aorta; Disease Models, Animal; Fibrillin-1; Humans; Losartan; Lung; Marfan Syndrome; Mice;	2016
A small molecule for a large disease. The New England journal of medicine, 2008, Jun-26, Volume: 358, Issue:26 Topics: Angiotensin II Type 1 Receptor Blockers; History, 20th Century; Humans; Losartan; Marfan Syndrome; T	2008
Targeting TGF-beta and the extracellular matrix in Marfan's syndrome. Developmental cell, 2008, Volume: 15, Issue:1 Topics: Angiotensin II Type 1 Receptor Blockers; Child; Disease Progression; Extracellular Matrix; Fibrillin	2008
Angiotensin II blockade in Marfan's syndrome. The New England journal of medicine, 2008, Oct-16, Volume: 359, Issue:16 Topics: Angiotensin II Type 1 Receptor Blockers; Benzamides; Fibrillins; Humans; Imatinib Mesylate; Losartan	2008
Angiotensin II blockade in Marfan's syndrome. The New England journal of medicine, 2008, Oct-16, Volume: 359, Issue:16 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Child; Fibrillins; Humans; Losartan; Marfan Syndro	2008
Circulating transforming growth factor-beta in Marfan syndrome. Circulation, 2009, Aug-11, Volume: 120, Issue:6 Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Animals; Aorta; Biomarkers; Echocardiography; Female	2009
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
Loeys-Dietz syndrome: a Marfan-like syndrome associated with aggressive vasculopathy. Singapore medical journal, 2009, Volume: 50, Issue:10 Topics: Anti-Arrhythmia Agents; Aortic Aneurysm; Echocardiography; Female; Humans; Infant, Newborn; Loeys-Di	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
Marfan syndrome and focal segmental glomerulosclerosis: a novel association. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia, 2010, Volume: 21, Issue:4 Topics: Adolescent; Adrenal Cortex Hormones; Antihypertensive Agents; Fibrillins; Follow-Up Studies; Glomeru	2010
Differential effects of alendronate and losartan therapy on osteopenia and aortic aneurysm in mice with severe Marfan syndrome. Human molecular genetics, 2010, Dec-15, Volume: 19, Issue:24 Topics: Alendronate; Animals; Aorta; Aortic Aneurysm; Bone Diseases, Metabolic; Bone Morphogenetic Proteins;	2010
Medicine. Frightening risk of Marfan syndrome, and potential treatment, elucidated. Science (New York, N.Y.), 2011, Apr-15, Volume: 332, Issue:6027 Topics: Animals; Aortic Aneurysm; Clinical Trials as Topic; Extracellular Signal-Regulated MAP Kinases; Huma	2011
Noncanonical TGFβ signaling contributes to aortic aneurysm progression in Marfan syndrome mice. Science (New York, N.Y.), 2011, Apr-15, Volume: 332, Issue:6027 Topics: Animals; Anthracenes; Aorta; Aortic Aneurysm; Diphenylamine; Disease Models, Animal; Disease Progres	2011
Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK antagonism. Science (New York, N.Y.), 2011, Apr-15, Volume: 332, Issue:6027 Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; A	2011
Pravastatin reduces Marfan aortic dilation. Circulation, 2011, Sep-13, Volume: 124, Issue:11 Suppl Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aorta; Aortic Diseases; Dilatation, Pathologic; Di	2011
miR-29b participates in early aneurysm development in Marfan syndrome. Circulation research, 2012, Jan-20, Volume: 110, Issue:2 Topics: Age Factors; Angiotensin II Type 1 Receptor Blockers; Animals; Aorta; Aortic Aneurysm; Apoptosis; Ap	2012
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
MMP-2 regulates Erk1/2 phosphorylation and aortic dilatation in Marfan syndrome. Circulation research, 2012, Jun-08, Volume: 110, Issue:12 Topics: Animals; Aorta, Thoracic; Disease Progression; Doxycycline; Drug Therapy, Combination; Losartan; MAP	2012
Medicine. Old drug, new hope for Marfan syndrome. Science (New York, N.Y.), 2006, Apr-07, Volume: 312, Issue:5770 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Animals; Aortic Aneurysm; Clin	2006
Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science (New York, N.Y.), 2006, Apr-07, Volume: 312, Issue:5770 Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Animals; Antibodies; Aorta; Ao	2006
Drug shows promise for marfan syndrome. JAMA, 2006, May-03, Volume: 295, Issue:17 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Fibrillins; Humans; Losartan; Marfan Syndrome; Mic	2006
Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states. Nature medicine, 2007, Volume: 13, Issue:2 Topics: Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Animals; Antibodies; Fibrillin-1; Fib	2007
ACE inhibitor bulks up muscle. Nature medicine, 2007, Volume: 13, Issue:2 Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Losartan; Marfan Syndrome; Mice; Models, Biologica	2007
Studies point way to new therapeutic prospects for muscular dystrophy. JAMA, 2007, Sep-26, Volume: 298, Issue:12 Topics: Animals; Codon, Nonsense; Dystrophin; Gene Expression; Humans; Losartan; Marfan Syndrome; Mice; Musc	2007

losartan and Marfan Syndrome