Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials

被引：61

作者：

Pitcher, Alex ^{[1
,26
]}

Spata, Enti ^{[2
,3
,4
]}

Emberson, Jonathan ^{[2
,3
,4
]}

Davies, Kelly ^{[2
,3
,4
]}

Halls, Heather ^{[2
,3
,4
]}

Holland, Lisa ^{[2
,3
,4
]}

Wilson, Kate ^{[3
,4
]}

Reith, Christina ^{[3
,4
]}

Child, Anne H. ^{[5
,6
]}

Clayton, Tim ^{[7
]}

Dodd, Matthew ^{[7
]}

Flather, Marcus ^{[8
]}

Jin, Xu Yu ^{[1
]}

Sandor, George ^{[9
]}

Groenink, Maarten ^{[10
,29
]}

Mulder, Barbara ^{[10
,29
]}

De Backer, Julie ^{[11
,12
,30
]}

Evangelista, Arturo ^{[13
,31
]}

Forteza, Alberto ^{[14
]}

Teixido-Tura, Gisela ^{[15
,31
]}

Boileau, Catherine ^{[16
,17
,18
,19
,32
]}

Jondeau, Guillaume ^{[16
,17
,18
,19
,32
]}

Milleron, Olivier ^{[16
,17
,18
,19
,32
]}

Lacro, Ronald, V ^{[20
,21
]}

Sleeper, Lynn A. ^{[20
,21
]}

Chiu, Hsin-Hui ^{[22
]}

Wu, Mei-Hwan ^{[23
,24
]}

Neubauer, Stefan ^{[25
]}

Watkins, Hugh ^{[26
]}

Dietz, Hal ^{[27
,28
]}

Baigent, Colin ^{[2
,3
,4
]}

机构：

[1] Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Heart Ctr, Oxford, England

[2] Univ Oxford, Nuffield Dept Populat Hlth, MRC Populat Hlth Res Unit, Oxford, England

[3] Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England

[4] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England

[5] Imperial Coll London, Guys & St Thomas NHS Trust, Royal Brompton & Harefield Hosp Unit, London, England

[6] Imperial Coll London, Dept Surg & Oncol, London, England

[7] London Sch Hyg & Trop Med, Dept Med Stat, Clin Trials Unit, London, England

[8] Univ East Anglia, Fac Med & Hlth Sci, Norwich, Norfolk, England

[9] Univ British Columbia, Dept Paediat, Fac Med, Vancouver, BC, Canada

[10] Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands

[11] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium

[12] Ghent Univ Hosp, Dept Cardiol, Ghent, Belgium

[13] Hosp Univ Vall dHebron, Serv Cardiol, Barcelona, Spain

[14] Hosp Puerta de Hierro, Majadahonda, Spain

[15] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Vall dHebron Inst Recerca, Dept Cardiol,CIBER CV, Barcelona, Spain

[16] Univ Paris Cite, F-75018 Paris, France

[17] Univ Sorbonne Paris Nord, INSERM, U1148, LVTS, F-75018 Paris, France

[18] Hop Bichat Claude Bernard, AP HP, Serv Cardiol, F-75018 Paris, France

[19] Hop Bichat Claude Bernard, AP HP, CRMR Syndrome Marfan & Apparentes, F-75018 Paris, France

[20] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA

[21] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[22] Buddhist Tzu Chi Med Fdn, Taipei Tzu Chi Hosp, Dept Pediat, New Taipei, Taiwan

[23] Natl Taiwan Univ Hosp, Dept Pediat, Taipei, Taiwan

[24] Natl Taiwan Univ Hosp, Adult Congenital Heart Ctr, Taipei, Taiwan

[25] Univ Oxford, Oxford Ctr Clin Magnet Resonance Res, Div Cardiovasc Med, Oxford, England

[26] Univ Oxford, Radcliffe Dept Med, Oxford, England

[27] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

[28] Johns Hopkins Univ, Sch Med, Dept Genet Med, Baltimore, MD USA

[29] HTAD Rare Dis Working Grp, European Reference Network Rare Multisyst Vasc Di, Amsterdam, Netherlands

[30] HTAD Rare Dis Working Grp, European Reference Network Rare Multisyst Vasc Di, Ghent, Belgium

[31] HTAD Rare Dis Working Grp, European Reference Network Rare Multisyst Vasc Di, Barcelona, Spain

[32] HTAD Rare Dis Working Grp, European Reference Network Rare Multisyst Vasc Di, Paris, France

来源：

LANCET | 2022年 / 400卷 / 10355期

基金：

英国医学研究理事会;

关键词：

AORTIC-ROOT DILATION; LOSARTAN VS. ATENOLOL; DOUBLE-BLIND; ASCENDING AORTA; SURFACE-AREA; YOUNG-ADULTS; CHILDREN; PROGRESSION; PREVENTION; BLOCKADE;

D O I：

10.1016/S0140-6736(22)01534-3

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Angiotensin receptor blockers (ARBs) and beta blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments. Methods In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus beta blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus beta blocker; and indirectly, beta blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva. Findings We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0.07 [SE 0.02] ARB vs 0.13 [SE 0.02] control; absolute difference -0.07 [95% CI -0.12 to -0.01]; p=0.012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0.0050), and there was no evidence to suggest that the effect of ARB varied with beta-blocker use (heterogeneity p=0.54). Three trials involving 766 eligible participants compared ARBs with beta blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0.08 [SE 0.03] in ARB groups vs -0.11 [SE 0.02] in beta-blocker groups; absolute difference 0.03 [95% CI -0.05 to 0.10]; p=0.48). Thus, indirectly, the difference in the annual change in the aortic root Z score between beta blockers and control was -0.09 (95% CI -0.18 to 0.00; p=0.042). Interpretation In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a beta blocker. The effects of beta blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and beta blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

引用

页码：822 / 831

页数：10

共 39 条

[1] Meta-analysis Examining the Usefulness of Angiotensin Receptor blockers for the Prevention of Aortic Root Dilation in Patients With the Marfan Syndrome [J].

Al-abcha, Abdullah ;

Saleh, Yehia ;

Mujer, Mark ;

Boumegouas, Manel ;

Herzallah, Khader ;

Charles, Lawrenshey ;

Elkhatib, Layan ;

Abdelkarim, Ola ;

Kehdi, Michael ;

Abela, George S. .

AMERICAN JOURNAL OF CARDIOLOGY, 2020, 128 :101-106

[2]

[Anonymous], Abous Us

[3] Applying Massive Parallel Sequencing to Molecular Diagnosis of Marfan and Loeys-Dietz Syndromes [J].

Baetens, Machteld ;

Van Laer, Lut ;

De Leeneer, Kim ;

Hellemans, Jan ;

De Schrijver, Joachim ;

Van De Voorde, Hendrik ;

Renard, Marjolijn ;

Dietz, Hal ;

Lacro, Ronald V. ;

Menten, Bjorn ;

Van Criekinge, Wim ;

De Backer, Julie ;

De Paepe, Anne ;

Loeys, Bart ;

Coucke, Paul J. .

HUMAN MUTATION, 2011, 32 (09) :1053-1062

[4] Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials [J].

Bhala, N. ;

Emberson, J. ;

Merhi, A. ;

Abramson, S. ;

Arber, N. ;

Baron, J. A. ;

Bombardier, C. ;

Cannon, C. ;

Farkouh, M. E. ;

FitzGerald, G. A. ;

Goss, P. ;

Halls, H. ;

Hawk, E. ;

Hawkey, C. ;

Hennekens, C. ;

Hochberg, M. ;

Holland, L. E. ;

Kearney, P. M. ;

Laine, L. ;

Lanas, A. ;

Lance, P. ;

Laupacis, A. ;

Oates, J. ;

Patrono, C. ;

Schnitzer, T. J. ;

Solomon, S. ;

Tugwell, P. ;

Wilson, K. ;

Wittes, J. ;

Baigent, C. ;

Adelowo, O. ;

Aisen, P. ;

Al-Quorain, A. ;

Altman, R. ;

Bakris, G. ;

Baumgartner, H. ;

Bresee, C. ;

Carducci, M. ;

Chang, D-M. ;

Chou, C-T. ;

Clegg, D. ;

Cudkowicz, M. ;

Doody, L. ;

El Miedany, Y. ;

Falandry, C. ;

Farley, J. ;

Ford, L. ;

GarciLosa, M. ;

Gonzalez-Ortiz, M. ;

Haghighi, M. .

LANCET, 2013, 382 (9894) :769-779

[5] Distinct effects of losartan and atenolol on vascular stiffness in Marfan syndrome [J].

Bhatt, Ami B. ;

Buck, J. Stewart ;

Zuflacht, Jonah P. ;

Milian, Jessica ;

Kadivar, Samoneh ;

Gauvreau, Kimberlee ;

Singh, Michael N. ;

Creager, Mark A. .

VASCULAR MEDICINE, 2015, 20 (04) :317-325

[6] Angiotensin II blockade and aortic-root dilation in Marfan's syndrome [J].

Brooke, Benjamin S. ;

Habashi, Jennifer P. ;

Judge, Daniel P. ;

Patel, Nishant ;

Loeys, Bart ;

Dietz, Harry C., III .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (26) :2787-2795

[7] Reference Values for Echocardiographic Assessment of the Diameter of the Aortic Root and Ascending Aorta Spanning All Age Categories [J].

Campens, Laurence ;

Demulier, Laurent ;

De Groote, Katya ;

Vandekerckhove, Kristof ;

De Wolf, Daniel ;

Roman, Mary J. ;

Devereux, Richard B. ;

De Paepe, Anne ;

De Backer, Julie .

AMERICAN JOURNAL OF CARDIOLOGY, 2014, 114 (06) :914-920

[8] Losartan Added to β-Blockade Therapy for Aortic Root Dilation in Marfan Syndrome: A Randomized, Open-Label Pilot Study [J].

Chiu, Hsin-Hui ;

Wu, Mei-Hwan ;

Wang, Jou-Kou ;

Lu, Chun-Wei ;

Chiu, Shuenn-Nan ;

Chen, Chun-An ;

Lin, Ming-Tai ;

Hu, Fu-Chang .

MAYO CLINIC PROCEEDINGS, 2013, 88 (03) :271-276

[9]

DePaepe A, 1996, AM J MED GENET, V62, P417, DOI 10.1002/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO

[10]

2-R

← 1 2 3 4 →