{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:44:53Z","timestamp":1790444693563,"version":"4.1.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2025,3,11]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Vascular Ehlers-Danlos syndrome is a rare genetic disorder characterized by defective type III collagen and a high risk of arterial morbidity and mortality. Several cardiovascular drugs are used for treatment, including celiprolol, but no controlled trial in this condition has been conducted to date. We hypothesized the benefit of the addition of an angiotensin II receptor blocker.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>A multicenter, randomized, placebo-controlled trial was conducted to assess the efficacy and safety of the angiotensin II receptor blocker irbesartan in adults with vascular Ehlers-Danlos syndrome on stable background celiprolol therapy. Patients were randomized 1:1 to receive irbesartan (150 mg\/day titrated to 300 mg\/day) or placebo for 2 years. The composite primary outcome was defined as any vascular Ehlers-Danlos syndrome\u2013related fatal or nonfatal arterial event or any new or worsening arterial lesions detected by systematic head-to-pelvis computed tomography angiography or peripheral arterial duplex ultrasound at different time points, using a time-to-first-event analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Twenty-nine participants (62% female; 40.3\u00b111.3 years of age) were randomized to irbesartan, and 28 (64% female; 40.7\u00b111.0 years of age) were randomized to placebo. The composite primary outcome occurred in 8 of 29 patients (27.6%) receiving irbesartan versus 15 of 28 patients (53.6%) receiving placebo (hazard ratio, 0.42 [95% CI, 0.17, 0.99];\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05). The risk of recurrent symptomatic or nonsymptomatic arterial events was lower with irbesartan than with placebo (risk ratio, 0.37 [95% CI, 0.19, 0.68];\n              <jats:italic>P<\/jats:italic>\n              =0.002). A reduction of progression of arterial lesions was observed at all sites. Irbesartan significantly reduced systolic blood pressure compared with placebo (baseline-adjusted difference of 5.4 mm Hg [\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001]), but no relation was observed with the reduction of the primary composite outcome. Eleven episodes of irbesartan-related hypotension were recorded, leading to a downtitration in 4 patients.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Compared with placebo, irbesartan reduced the risk of severe symptomatic and asymptomatic arterial events in patients with vascular Ehlers-Danlos syndrome on background celiprolol therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT02597361.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.124.072849","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T10:00:30Z","timestamp":1738749630000},"page":"686-695","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Efficacy of Irbesartan in Celiprolol-Treated Patients With Vascular Ehlers-Danlos Syndrome"],"prefix":"10.1161","volume":"151","clinical-trial-number":[{"clinical-trial-number":"nct02597361","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5925-381X","authenticated-orcid":true,"given":"Xavier","family":"Jeunemaitre","sequence":"first","affiliation":[{"name":"PARCC (X.J., E.M., P.B., T.M., G.C.), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 Paris Cit\u00e9, France."},{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine G\u00e9nomique des Maladies Rares et DMU BioPhyGen (X.J., C. Billon, M.B.Y.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8076-1445","authenticated-orcid":true,"given":"Elie","family":"Mousseaux","sequence":"additional","affiliation":[{"name":"PARCC (X.J., E.M., P.B., T.M., G.C.), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 Paris Cit\u00e9, France."},{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de Radiologie Vasculaire (E.M., F.P.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2286-2563","authenticated-orcid":true,"given":"Michael","family":"Frank","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine Vasculaire et Centre de R\u00e9f\u00e9rence des Maladies Art\u00e9rielles Rares (M.F., S.A., M.E.H., N.D., T.M.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2955-0922","authenticated-orcid":true,"given":"Salma","family":"Adham","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine Vasculaire et Centre de R\u00e9f\u00e9rence des Maladies Art\u00e9rielles Rares (M.F., S.A., M.E.H., N.D., T.M.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."},{"name":"Service de M\u00e9decine Vasculaire, H\u00f4pital Saint-Eloi, CHU Montpellier, France (S.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8718-9218","authenticated-orcid":true,"given":"Francesca","family":"Pitocco","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de Radiologie Vasculaire (E.M., F.P.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Billon","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine G\u00e9nomique des Maladies Rares et DMU BioPhyGen (X.J., C. Billon, M.B.Y.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molka","family":"Ben Yakhlef","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine G\u00e9nomique des Maladies Rares et DMU BioPhyGen (X.J., C. Billon, M.B.Y.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-4504","authenticated-orcid":true,"given":"Mohamed","family":"El Hachmi","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine Vasculaire et Centre de R\u00e9f\u00e9rence des Maladies Art\u00e9rielles Rares (M.F., S.A., M.E.H., N.D., T.M.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."},{"name":"Dipartimento Medicina Molecolare, University La Sapienza, Italy (M.E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7469-2407","authenticated-orcid":true,"given":"Alessandra","family":"Bura-Rivi\u00e8re","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Vasculaire, CHU de Toulouse, H\u00f4pital Rangueil, Toulouse, France (A.B.-R., F.-X.L.)."},{"name":"Unit\u00e9 Mixte de Recherche 1295 INSERM, Centre d\u2019Epid\u00e9miologie et de Recherche en Sant\u00e9 des Populations, Toulouse III-Paul Sabatier University, Toulouse, France (A.B.-R., F.-X.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3101-3889","authenticated-orcid":true,"given":"Fran\u00e7ois-Xavier","family":"Lap\u00e9bie","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Vasculaire, CHU de Toulouse, H\u00f4pital Rangueil, Toulouse, France (A.B.-R., F.-X.L.)."},{"name":"Unit\u00e9 Mixte de Recherche 1295 INSERM, Centre d\u2019Epid\u00e9miologie et de Recherche en Sant\u00e9 des Populations, Toulouse III-Paul Sabatier University, Toulouse, France (A.B.-R., F.-X.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-745X","authenticated-orcid":true,"given":"Claire","family":"Le Hello","sequence":"additional","affiliation":[{"name":"Departement de M\u00e9decine Vasculaire, CHU Caen Normandie, Caen, France (C.L.H.)."},{"name":"Service de M\u00e9decine Vasculaire, CHU St-Etienne, H\u00f4pital Nord, St-Etienne, France (C.L.H.)."},{"name":"INSERM, U1059, Universit\u00e9 Jean Monnet, St-Etienne, France (C.L.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0598-3929","authenticated-orcid":true,"given":"Damien","family":"Laneelle","sequence":"additional","affiliation":[{"name":"INSERM, COMETE, GIP Cyceron, Universit\u00e9 de Caen Normandie, Caen, France (D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7444-7938","authenticated-orcid":true,"given":"Christophe","family":"Seinturier","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Vasculaire, CHU Grenoble Alpes, Grenoble, France (C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4362-4062","authenticated-orcid":true,"given":"Klaus","family":"Dieterich","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU Grenoble, Universit\u00e9 Grenoble Alpes, INSERM 1209, Institut pour l\u2019Avanc\u00e9e des Biosciences, Grenoble University Hospital, France (K.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lambert","sequence":"additional","affiliation":[{"name":"Unit\u00e9 M\u00e9dico Chirurgicale Vasculaire, Service de M\u00e9decine Interne, H\u00f4pital Claude Huriez, CHRU Lille, France (M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8834-5526","authenticated-orcid":true,"given":"Sophie","family":"Dupuis-Girod","sequence":"additional","affiliation":[{"name":"National HHT Reference Center and Genetics Department, Hospices Civils de Lyon, Femme-Me\u0300re-Enfants Hospital, Bron, France (S.D.-G.)."},{"name":"INSERM, Biosant\u00e9 Unit U1292, Universit\u00e9 Grenoble Alpes, CEA, Grenoble, France (S.D.-G., P.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9326-6881","authenticated-orcid":true,"given":"St\u00e9phane","family":"Zuily","sequence":"additional","affiliation":[{"name":"CHRU Nancy, Service de M\u00e9decine Vasculaire, Centre de R\u00e9f\u00e9rence pour les Maladies Auto-immunes et Auto-inflammatoires, Centre de Comp\u00e9tence pour les Maladies Vasculaires Rares, H\u00f4pitaux de Brabois, Vandoeuvre-l\u00e8s-Nancy, France (S.Z.)."},{"name":"INSERM, U1116, D\u00e9faillance Cardiovasculaire Aigu\u00eb et Chronique, Universit\u00e9 de Lorraine, Nancy, France (S.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7883-5716","authenticated-orcid":true,"given":"Laurence","family":"Bal-Theoleyre","sequence":"additional","affiliation":[{"name":"AP-HM, CHU La Timone, Centre de R\u00e9f\u00e9rence Pour le Syndrome de Marfan et Apparent\u00e9s, Centre Aorte Timone, Universit\u00e9 Aix-Marseille, Marseille, France (L.B.-T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Boulon","sequence":"additional","affiliation":[{"name":"H\u00f4pital Saint-Andr\u00e9, CHU Bordeaux, France (C. Boulon)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierrick","family":"Henneton","sequence":"additional","affiliation":[{"name":"INSERM, Biosant\u00e9 Unit U1292, Universit\u00e9 Grenoble Alpes, CEA, Grenoble, France (S.D.-G., P.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4817-0056","authenticated-orcid":true,"given":"Estelle","family":"Lu","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche Clinique (E.L., G.C.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Denari\u00e9","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine Vasculaire et Centre de R\u00e9f\u00e9rence des Maladies Art\u00e9rielles Rares (M.F., S.A., M.E.H., N.D., T.M.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-3569","authenticated-orcid":true,"given":"Pierre","family":"Boutouyrie","sequence":"additional","affiliation":[{"name":"PARCC (X.J., E.M., P.B., T.M., G.C.), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 Paris Cit\u00e9, France."},{"name":"Service de Pharmacologie (P.B.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8690-1093","authenticated-orcid":true,"given":"Tristan","family":"Mirault","sequence":"additional","affiliation":[{"name":"PARCC (X.J., E.M., P.B., T.M., G.C.), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 Paris Cit\u00e9, France."},{"name":"AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Service de M\u00e9decine Vasculaire et Centre de R\u00e9f\u00e9rence des Maladies Art\u00e9rielles Rares (M.F., S.A., M.E.H., N.D., T.M.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6373-8956","authenticated-orcid":true,"given":"Gilles","family":"Chatellier","sequence":"additional","affiliation":[{"name":"PARCC (X.J., E.M., P.B., T.M., G.C.), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 Paris Cit\u00e9, France."},{"name":"Unit\u00e9 de Recherche Clinique (E.L., G.C.), AP-HP, H\u00f4pital Europ\u00e9en Georges-Pompidou, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0597-8318","authenticated-orcid":true,"given":"Michel","family":"Azizi","sequence":"additional","affiliation":[{"name":"CIC1418 (M.A.), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), Universit\u00e9 Paris 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