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

Muiño-Mosquera, Laura; Nobele, Sylvia De; Devos, Daniël; Campens, Laurence; Paepe, Anne De; Backer, Julie De

doi:10.1080/00015385.2017.1314134

Cited by 37 publications

(38 citation statements)

References 26 publications

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“…The final analysis included seven clinical trials [1–5, 7, 8], with a total of 1352 patients and average weighted follow-up of 37.8 months (Fig. 1; Supplemental Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…The results showed a lower degree of heterogeneity by excluding the studies by Lacro et al [2] and Chiu et al [4] (MD = −0.07; 95% CI −0.08 to −0.05; p < 0.001; I 2 = 24%). Subgroup analysis according to the control group showed no significant subgroup interaction when comparing losartan with beta-blockers [1, 2, 4, 7] versus with standard therapy [3, 5, 8] ( p interaction = 0.27). A change in the diameter of the ascending aorta was reported in six studies, and analysis showed no significant difference between the losartan and control groups (MD = −0.02; 95% CI −0.14 to −0.11; p = 0.78; I 2 = 98%).…”

Section: Resultsmentioning

confidence: 99%

“…The only available meta-analysis of randomized trials suffered major drawbacks in its methodology with double counting subjects from one study [6]. The extended follow-up results of the LOAT (losartan vs. atenolol) trial and two other randomized trials were recently presented [1, 7, 8]. Hence, we performed a meta-analysis of the available randomized clinical trials evaluating the efficacy of losartan in the prevention of aortic dilatation.…”

Section: Introductionmentioning

confidence: 99%

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Losartan for Preventing Aortic Root Dilatation in Patients with Marfan Syndrome: A Meta-Analysis of Randomized Trials

et al. 2019

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IntroductionThe role of losartan in preventing aortic root dilatation in Marfan syndrome has been evaluated in many clinical trials; however, the results are conflicting.MethodsWe performed a computerized search of MEDLINE, EMBASE and COCHRANE databases through February 2019 for randomized clinical trials evaluating the effect of losartan in patients with Marfan syndrome. The main outcome was the change in the aortic root diameter in the losartan versus control groups.ResultsOur final analysis included seven randomized trials with a total of 1352 patients and average weighted follow-up of 37.8 months. Change in aortic root diameter was significantly smaller with losartan compared with control [weighted means: 0.44 vs. 0.58 mm, mean difference (MD) = −0.13; 95% CI −0.24 to −0.02; p = 0.02]. Subgroup analysis according to the control group showed no significant subgroup interaction when comparing losartan with beta-blockers versus with standard therapy (pinteraction= 0.27). The composite outcome of aortic surgery, dissection or mortality did not differ between the losartan and control groups (risk ratio = 1.03; 95% CI 0.72–1.49, p = 0.86).ConclusionIn this meta-analysis including seven randomized trials, the use of losartan was associated with a significantly smaller change in aortic root diameter in patients with Marfan syndrome.Electronic supplementary materialThe online version of this article (10.1007/s40119-019-00149-3) contains supplementary material, which is available to authorized users.

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“…The final analysis included seven clinical trials [1–5, 7, 8], with a total of 1352 patients and average weighted follow-up of 37.8 months (Fig. 1; Supplemental Table 1).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Losartan for Preventing Aortic Root Dilatation in Patients with Marfan Syndrome: A Meta-Analysis of Randomized Trials

et al. 2019

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“…Chiu et al [ 72 ] reported that addition of Losartan to beta-blockers in a young patient group did result in reduced rate of aortic dilatation, although the annual rate of aortic dilatation amongst those receiving only beta-blockers was greater than that reported in any other clinical study. In contrast, neither the Ghent [ 73 ] nor the Vancouver [ 74 ] studies observed any apparent benefit from Losartan treatment, with the latter study conducted in a similar age group to the Taiwan study.…”

Section: Angiotensin II and Aortic Aneurysm In Marfan Syndrome - Clinmentioning

confidence: 93%

Angiotensin, transforming growth factor β and aortic dilatation in Marfan syndrome: Of mice and humans

Jeremy

2018

IJC Heart & Vasculature

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Marfan syndrome is consequent upon mutations in FBN1, which encodes the extracellular matrix microfibrillar protein fibrillin-1. The phenotype is characterised by development of thoracic aortic aneurysm. Current understanding of the pathogenesis of aneurysms in Marfan syndrome focuses upon abnormal vascular smooth muscle cell signalling through the transforming growth factor beta (TGFβ) pathway. Angiotensin II (Ang II) can directly induce aortic dilatation and also influence TGFβ synthesis and signalling. It has been hypothesised that antagonism of Ang II signalling may protect against aortic dilatation in Marfan syndrome. Experimental studies have been supportive of this hypothesis, however results from multiple clinical trials are conflicting. This paper examines current knowledge about the interactions of Ang II and TGFβ signalling in the vasculature, and critically interprets the experimental and clinical findings against these signalling interactions.

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“…Experimental models of Marfan syndrome suggest that angiotensin-II type 1 receptor blockers (ARBs) can alter biological pathways, including excessive TGF-β signalling, that might contribute to the pathogenesis of aortic complications,5, 6, 7, 8 a finding that is supported by observational data in clinical studies 9 . Randomised trials in Marfan syndrome have compared the effects of the ARB losartan with either β blockers or control (where standard medical therapy could include β blockers) on aortic dilatation10, 11, 12, 13, 14, 15 without clear evidence of benefit. Other ARBs, such as irbesartan, might have greater bioavailability and a longer half-life than losartan with more potent antihypertensive effects.…”

Section: Introductionmentioning

confidence: 99%

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

et al. 2019

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SummaryBackgroundIrbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome.MethodsWe did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794.FindingsBetween March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events.InterpretationIrbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications.FundingBritish Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

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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

Cited by 37 publications

References 26 publications

Losartan for Preventing Aortic Root Dilatation in Patients with Marfan Syndrome: A Meta-Analysis of Randomized Trials

Losartan for Preventing Aortic Root Dilatation in Patients with Marfan Syndrome: A Meta-Analysis of Randomized Trials

Angiotensin, transforming growth factor β and aortic dilatation in Marfan syndrome: Of mice and humans

Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial

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