Angiotensin II receptor blockers in pregnancy: a case report and systematic review of the literature.
ABSTRACT To describe the case of a woman exposed to angiotensin-II receptor blockers (ARBs) in the preconceptional period and to systematically review the literature on the safety of these drugs when used by pregnant women.
The case was identified at the Korean Motherisk Program (Seoul). For the systematic review, we searched the PubMed for case reports, case series, and post-marketing surveys.
A hypertensive woman was exposed to irbesartan prior to conception. The embryo had delayed development of upper and lower extremities and decreased digital groove. A karyotype identified a 45,XO Turner syndrome. The patient had a spontaneous abortion. Including the case reported here, 64 published cases were identified in total; 57.8% had favorable and 42.2% had unfavorable outcomes. Duration of treatment during pregnancy among women who had adverse fetal outcomes was 26.3 +/- 10.5 weeks (mean +/- SD), compared with 17.3 +/- 11.6 weeks in those who had favorable outcomes (p = 0.04).
Exposure to ARBs for a period longer than the first trimester of pregnancy appears to be associated with a high risk for adverse fetal outcomes.
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ABSTRACT: to assess whether the incidence of angiotensin II-receptor type 1antagonist (AT1-anta-gonist) - or ACE-inhibitor induced cases of oligohydramnios sequence (OHS) in 2011 was reduced after intensive alerts as to the causal association between AT1-antagonist /ACE-inhibitor and OHS in the German medical literature.3 sources of information were used: A nationwide active surveillance of OHS in German paediatric hospitals (ESPED); Embryotox, (Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy) and screening of pubmed (AT1-antagonist/ACE-inhibitor induced OHS).45 cases of OHS were identified, no case due to maternal AT1-antagonist/ACE-inhibitor treatment. Causes for OHS were: premature rupture of membranes (PPROM) (n=28), congenital anomalies of fetal kidneys and urinary tract (CAKUT (n=15), placental insufficiency (n=1), unknown cause (n=1). Mortality until discharge was 37.8% (32.1% PPROM, 57.1% CAKUT). Embryotox identified 3 exposures to AT1-antagonists in pregnancy, no case was associated with OHS. The pubmed search did not identify any case of OHS related to AT1-antagonist/ACE-inhibitor in pregnancy in Germany in 2011.Treatment of pregnant women with ACE inhibitors or AT1-antagonists still occurs but no cases of AT1-antagonist- or ACE-inhibitor induced OHS were reported in 2011 in Germany most likely due to repeated published alerts underlining the importance of consequent education. OHS remains a serious condition with high mortality despite modern intensive care.Klinische Pädiatrie 03/2014; 226(2). DOI:10.1055/s-0033-1363267 · 1.90 Impact Factor
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ABSTRACT: Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [angiotensin-(1-9)], Ang-(1-7) [angiotensin-(1-7)] and the Mas receptor was discovered. Activation of this novel pathway stimulates vasodilation, anti-hypertrophy and anti-hyperplasia. For some time, studies have focused mainly on ACE2, Ang-(1-7) and the Mas receptor, and their biological properties that counterbalance the ACE/AngII/AT1R (angiotensin type 1 receptor) axis. No previous information about Ang-(1-9) suggested that this peptide had biological properties. However, recent data suggest that Ang-(1-9) protects the heart and blood vessels (and possibly the kidney) from adverse cardiovascular remodelling in patients with hypertension and/or heart failure. These beneficial effects are not modified by the Mas receptor antagonist A779 [an Ang-(1-7) receptor blocker], but they are abolished by the AT2R (angiotensin type 2 receptor) antagonist PD123319. Current information suggests that the beneficial effects of Ang-(1-9) are mediated via the AT2R. In the present review, we summarize the biological effects of the novel vasoactive peptide Ang-(1-9), providing new evidence of its cardiovascular-protective activity. We also discuss the potential mechanism by which this peptide prevents and ameliorates the cardiovascular damage induced by RAS activation.
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ABSTRACT: Little is known about the biological effects of angiotensin-(1-9), but available evidence shows that angiotensin-(1-9) has beneficial effects in preventing/ameliorating cardiovascular remodeling. In this study, we evaluated whether angiotensin-(1-9) decreases hypertension and reverses experimental cardiovascular damage in the rat. Angiotensin-(1-9) (600 ng/kg per min for 2 weeks) reduced already-established hypertension in rats with early high blood pressure induced by angiotensin II infusion or renal artery clipping. Angiotensin-(1-9) also improved cardiac (assessed by echocardiography) and endothelial function in small-diameter mesenteric arteries, cardiac and aortic wall hypertrophy, fibrosis, oxidative stress, collagen and transforming growth factor type β - 1 protein expression (assessed by western blot). The beneficial effect of angiotensin-(1-9) was blunted by coadministration of the angiotensin type 2(AT2) receptor blocker PD123319 (36 ng/kg per min) but not by coadministration of the Mas receptor blocker A779 (100 ng/kg per min). Angiotensin-(1-9) treatment also decreased circulating levels of Ang II, angiotensin-converting enzyme activity and oxidative stress in aorta and left ventricle. Whereas, Ang-(1-9) increased endothelial nitric oxide synthase mRNA levels in aorta as well as plasma nitrate levels. Angiotensin-(1-9) reduces hypertension, ameliorates structural alterations (hypertrophy and fibrosis), oxidative stress in the heart and aorta and improves cardiac and endothelial function in hypertensive rats. These effects were mediated by the AT2 receptor but not by the angiotensin-(1-7)/Mas receptor axis.Journal of Hypertension 01/2014; DOI:10.1097/HJH.0000000000000094 · 4.22 Impact Factor