{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:15:09Z","timestamp":1760058909843,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Introduction: Placebo-controlled studies are crucial in clinical trials, but the placebo effect can vary across conditions. We aimed to assess the placebo effect in chronic thromboembolic pulmonary hypertension (CTEPH) trials. Methods: We conducted a systematic review and included randomized placebo-controlled trials investigating CTEPH interventions. Primary outcomes were the pre\u2013post changes in the 6 min walk test (6MWT) and quality of life in the placebo arms. Secondary outcomes included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and NT-proBNP levels. Meta-analyses were performed using random-effects models. Results: Seven trials with 270 CTEPH patients in placebo arms were analyzed. The average 6MWT change was not significant (\u22121.31 m; 95%CI \u221212.49 to +9.79). Quality of life with EQ-5D was not significantly improved (\u22120.04; 95%CI \u22120.10 to +0.02). mPAP, PVR, cardiac index, and NT-proBNP also demonstrated non-significant changes with small magnitudes. Conclusions: The placebo effect in CTEPH trials was not statistically significant and had small magnitude but should not discourage the use of placebo-controlled trials where applicable and ethical.<\/jats:p>","DOI":"10.3390\/medsci13020057","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T04:20:26Z","timestamp":1746591626000},"page":"57","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Placebo Effect in Chronic Thromboembolic Pulmonary Hypertension Trials: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-5673","authenticated-orcid":false,"given":"Daniel","family":"Caldeira","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Departamento de Cora\u00e7\u00e3o e Vasos, Centro Hospital Universit\u00e1rio Lisboa Norte (CHULN), Unidade Local de Saude Santa Maria, Centro Acad\u00e9mico de Medicina de Lisboa, 1649-035 Lisboa, Portugal"},{"name":"Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Centro de Estudos de Medicina Baseada na Evid\u00eancia (CEMBE), Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0277-7398","authenticated-orcid":false,"given":"Daniel In\u00e1cio","family":"Cazeiro","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Departamento de Cora\u00e7\u00e3o e Vasos, Centro Hospital Universit\u00e1rio Lisboa Norte (CHULN), Unidade Local de Saude Santa Maria, Centro Acad\u00e9mico de Medicina de Lisboa, 1649-035 Lisboa, Portugal"}]},{"given":"Rui","family":"Pl\u00e1cido","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Departamento de Cora\u00e7\u00e3o e Vasos, Centro Hospital Universit\u00e1rio Lisboa Norte (CHULN), Unidade Local de Saude Santa Maria, Centro Acad\u00e9mico de Medicina de Lisboa, 1649-035 Lisboa, Portugal"},{"name":"Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Filipa","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-2065","authenticated-orcid":false,"given":"Rita","family":"Cal\u00e9","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Hospital Garcia de Orta, 2805-267 Almada, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8034-4529","authenticated-orcid":false,"given":"Fausto J.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cardiologia, Departamento de Cora\u00e7\u00e3o e Vasos, Centro Hospital Universit\u00e1rio Lisboa Norte (CHULN), Unidade Local de Saude Santa Maria, Centro Acad\u00e9mico de Medicina de Lisboa, 1649-035 Lisboa, Portugal"},{"name":"Centro Cardiovascular da Universidade de Lisboa (CCUL@RISE), Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur. 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