{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:45:34Z","timestamp":1792025134440,"version":"4.4.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yuhan Corporation, Seoul, Republic of Korea"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence comparing different diuretic doses within fixed-dose combinations (FDCs) remains limited. We evaluated telmisartan\/chlorthalidone FDCs according to chlorthalidone dose in patients with blood pressure (BP) inadequately controlled on telmisartan monotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this randomized, double-blind trial, 254 patients with uncontrolled BP [sitting systolic blood pressure (SBP) \u2265140 and &amp;lt;180 mm Hg; sitting diastolic blood pressure (DBP) &amp;lt;110 mm Hg] after a telmisartan run-in period were randomized (1:1:1) to receive either telmisartan\/chlorthalidone FDCs (40\/12.5 or 40\/6.25 mg), or telmisartan 40 mg for 8 weeks. The primary endpoint was the change in sitting SBP from baseline to Week 8.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At Week 8, telmisartan\/chlorthalidone FDCs demonstrated greater reductions in sitting SBP compared with telmisartan \u00admonotherapy: least-squares mean differences were \u22129.5 mm Hg [95% CI, \u221213.5 to \u22125.6] for the 40\/12.5 mg and \u22126.1 mm Hg [95% CI, \u221210.4 to \u22121.9] for the 40\/6.25 mg. BP control rates (target BP: SBP\/DBP &amp;lt;140\/90 mm Hg, or &amp;lt;130\/80 mm Hg in patients with albuminuric chronic kidney disease or established cardiovascular disease) at Week 8 also favored telmisartan\/chlorthalidone FDCs over telmisartan monotherapy (53.2% for the 40\/12.5 mg and 43.0% for the 40\/6.25 mg vs 32.9% for telmisartan 40 mg). Safety profiles were comparable among treatment groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients inadequately controlled on telmisartan alone, FDCs of telmisartan with 2 different doses of chlorthalidone provided greater BP reduction than telmisartan monotherapy without increased safety risk, supporting its role as an effective and well-tolerated treatment option.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, NCT06291207.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajh\/hpag081","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:48:02Z","timestamp":1791460082000},"source":"Crossref","is-referenced-by-count":0,"title":["Telmisartan\u2013chlorthalidone fixed-dose combination at 2 chlorthalidone dose levels versus telmisartan in uncontrolled hypertension: a Phase III trial"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2662-5952","authenticated-orcid":false,"given":"Seung-Whan","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-3557","authenticated-orcid":false,"given":"Jin-Man","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-6678","authenticated-orcid":false,"given":"Soon Jun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7315-7557","authenticated-orcid":false,"given":"Seung Hwan","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine , Incheon,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-8791","authenticated-orcid":false,"given":"Gyu Chul","family":"Oh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-2713","authenticated-orcid":false,"given":"Seong Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine , Ansan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-5283","authenticated-orcid":false,"given":"Jung-Hoon","family":"Sung","sequence":"additional","affiliation":[{"name":"Division of Cardiology, CHA Bundang Medical Center, CHA University , Seongnam,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5845-2232","authenticated-orcid":false,"given":"Sang-Rok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Jeonbuk National University Hospital , Jeonju,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5846-0606","authenticated-orcid":false,"given":"Gyung-Min","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine , Ulsan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-1746","authenticated-orcid":false,"given":"Hyun-Jae","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6063-3083","authenticated-orcid":false,"given":"Jun-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-1522","authenticated-orcid":false,"given":"Ji-Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Daegu Catholic University Medical Center , Daegu,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7262-1848","authenticated-orcid":false,"given":"Kyung Hee","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Dong-A University Hospital, Dong-A University College of Medicine , Busan,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-9358","authenticated-orcid":false,"given":"Cheol Ung","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Cardiovascular Center, Korea University Guro Hospital , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2493-066X","authenticated-orcid":false,"given":"Byeong-Keuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Severance Cardiovascular Hospital, Yonsei University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8026-1582","authenticated-orcid":false,"given":"Sang-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiovascular Center, Seoul National University Boramae Medical Center, Seoul National University College of Medicine , Seoul,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1644-2105","authenticated-orcid":false,"given":"In-Ho","family":"Chae","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Seoul National University Bundang Hospital , Seongnam,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"2026101420021133700_hpag081-B1","volume-title":"Global Report on Hypertension 2025: High Stakes-Turning Evidence into Action","author":"World Health Organization","year":"2025"},{"key":"2026101420021133700_hpag081-B2","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/S0140-6736(20)30752-2","article-title":"Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"GBD 2019 Risk Factors Collaborators","year":"2020","journal-title":"Lancet"},{"key":"2026101420021133700_hpag081-B3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41581-019-0244-2","article-title":"The global epidemiology of hypertension","volume":"16","author":"Mills","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"2026101420021133700_hpag081-B4","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC guidelines for the management of elevated blood pressure and hypertension","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur Heart J"},{"key":"2026101420021133700_hpag081-B5","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1161\/HYP.0000000000000066","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology\/American Heart Association Task Force on clinical practice guidelines","volume":"71","author":"Whelton","year":"2018","journal-title":"Hypertension"},{"key":"2026101420021133700_hpag081-B6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jash.2010.02.005","article-title":"Combination therapy in hypertension","volume":"4","author":"Gradman","year":"2010","journal-title":"J Am Soc Hypertens"},{"key":"2026101420021133700_hpag081-B7","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/jhh.2009.90","article-title":"Effectiveness of initiating treatment with valsartan\/hydrochlorothiazide in patients with stage-1 or stage-2 hypertension","volume":"24","author":"Zappe","year":"2010","journal-title":"J Hum Hypertens"},{"key":"2026101420021133700_hpag081-B8","doi-asserted-by":"publisher","first-page":"e25810","DOI":"10.1161\/HYPERTENSIONAHA.125.25810","article-title":"Low-dose TEL\/AML\/CHTD SPC versus standard-dose TEL in hypertension: phase III RCT","volume":"83","author":"Ahn","year":"2026","journal-title":"Hypertension"},{"key":"2026101420021133700_hpag081-B9","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/s41371-019-0255-2","article-title":"Comparative efficacy and safety of chlorthalidone and hydrochlorothiazide\u2014meta-analysis","volume":"33","author":"Dineva","year":"2019","journal-title":"J Hum Hypertens"},{"key":"2026101420021133700_hpag081-B10","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1161\/HYPERTENSIONAHA.111.190637","article-title":"Meta-analysis of dose-response relationships for hydrochlorothiazide, chlorthalidone, and bendroflumethiazide on blood pressure, serum potassium, and urate","volume":"59","author":"Peterzan","year":"2012","journal-title":"Hypertension"},{"key":"2026101420021133700_hpag081-B11","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.jacc.2015.10.083","article-title":"Efficacy of low-dose chlorthalidone and hydrochlorothiazide as assessed by 24-h ambulatory blood pressure monitoring","volume":"67","author":"Pareek","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"2026101420021133700_hpag081-B12","author":"Ministry of Food and Drug Safety","year":"2023"},{"key":"2026101420021133700_hpag081-B13","author":"Ministry of Food and Drug Safety","year":"2018"},{"key":"2026101420021133700_hpag081-B14","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1517\/14656560902991514","article-title":"A randomized, comparative study evaluating the efficacy and tolerability of losartan-low dose chlorthalidone (6.25 mg) combination with losartan-hydrochlorothiazide (12.5 mg) combination in Indian patients with mild-to-moderate essential hypertension","volume":"10","author":"Pareek","year":"2009","journal-title":"Expert Opin Pharmacother"},{"key":"2026101420021133700_hpag081-B15","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/00045391-200203000-00005","article-title":"Comparison of a fixed-dose combination of 40 mg telmisartan plus 12.5 mg hydrochlorothiazide with 40 mg telmisartan in the control of mild to moderate hypertension","volume":"9","author":"Lacourci\u00e8re","year":"2002","journal-title":"Am J Ther"},{"key":"2026101420021133700_hpag081-B16","doi-asserted-by":"publisher","first-page":"6670183","DOI":"10.1155\/2021\/6670183","article-title":"Efficacy of ARB\/HCTZ combination therapy in uncontrolled hypertensive patients compared with ARB monotherapy: a meta-analysis","volume":"2021","author":"Ma","year":"2021","journal-title":"Int J Hypertens"},{"key":"2026101420021133700_hpag081-B17","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1185\/03007995.2014.924912","article-title":"Telmisartan in combination with hydrochlorothiazide 12.5\u2009mg for the management of patients with hypertension","volume":"30","author":"Neldam","year":"2014","journal-title":"Curr Med Res Opin"},{"key":"2026101420021133700_hpag081-B18","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.amjmed.2008.09.038","article-title":"Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials","volume":"122","author":"Wald","year":"2009","journal-title":"Am J Med"},{"key":"2026101420021133700_hpag081-B19","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/s0149-2918(01)80072-2","article-title":"Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial","volume":"23","author":"McGill","year":"2001","journal-title":"Clin Ther"},{"key":"2026101420021133700_hpag081-B20","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1291\/hypres.28.555","article-title":"Telmisartan\/hydrochlorothiazide in comparison with losartan\/hydrochlorothiazide in managing patients with mild-to-moderate hypertension","volume":"28","author":"Neutel","year":"2005","journal-title":"Hypertens Res"},{"key":"2026101420021133700_hpag081-B21","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1136\/bmj.326.7404.1427","article-title":"Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials","volume":"326","author":"Law","year":"2003","journal-title":"BMJ"},{"key":"2026101420021133700_hpag081-B22","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1097\/HJH.0000000000003480","article-title":"2023 ESH guidelines for the management of arterial hypertension the task force for the management of arterial hypertension of the European Society of Hypertension: endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)","volume":"41","author":"Mancia","year":"2023","journal-title":"J Hypertens"},{"key":"2026101420021133700_hpag081-B23","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/ajh\/hpab002","article-title":"Blood pressure control among older adults with hypertension: narrative review and introduction of a framework for improving care","volume":"34","author":"Bowling","year":"2021","journal-title":"Am J Hypertens"},{"key":"2026101420021133700_hpag081-B24","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1210\/jc.2019-00197","article-title":"Antihypertensive agents in older adults: a systematic review and meta-analysis of randomized clinical trials","volume":"104","author":"Murad","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2026101420021133700_hpag081-B25","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1001\/jama.288.23.2981","article-title":"Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)","volume":"288","author":"ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group","year":"2002","journal-title":". JAMA"},{"key":"2026101420021133700_hpag081-B26","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1056\/NEJMoa0801369","article-title":"Treatment of hypertension in patients 80 years of age or older","volume":"358","author":"Beckett","year":"2008","journal-title":"N Engl J Med"},{"key":"2026101420021133700_hpag081-B27","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1161\/HYPERTENSIONAHA.109.129171","article-title":"Thiazide effects and adverse effects: insights from molecular genetics","volume":"54","author":"Ellison","year":"2009","journal-title":"Hypertension"},{"key":"2026101420021133700_hpag081-B28","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1056\/NEJMra0907219","article-title":"Use of diuretics in patients with hypertension","volume":"361","author":"Ernst","year":"2009","journal-title":"N Engl J Med"}],"container-title":["American Journal of Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajh\/advance-article-pdf\/doi\/10.1093\/ajh\/hpag081\/71787873\/hpag081.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajh\/advance-article-pdf\/doi\/10.1093\/ajh\/hpag081\/71787873\/hpag081.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:02:17Z","timestamp":1792022537000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajh\/advance-article\/doi\/10.1093\/ajh\/hpag081\/8898622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":28,"URL":"https:\/\/doi.org\/10.1093\/ajh\/hpag081","relation":{},"ISSN":["0895-7061","1941-7225"],"issn-type":[{"value":"0895-7061","type":"print"},{"value":"1941-7225","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"article-number":"hpag081"}}