{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T06:52:22Z","timestamp":1774853542418,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Previous studies on the optimal timing for antihypertensive medication administration have yielded inconsistent results. While earlier meta-analyses indicated that bedtime dosing significantly reduces myocardial infarction (MI) risk, more recent research has presented conflicting evidence. Therefore, we aimed to evaluate the impact of bedtime\n                      <jats:italic>versus<\/jats:italic>\n                      morning dosing of antihypertensive drugs on cardiovascular outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic search across PubMed, EMBASE, and Web of Science databases, covering studies published from inception to 16 July 2025, to identify relevant randomized controlled trials. We calculated risk ratios (RRs) for dichotomous outcomes along with the corresponding 95% confidence intervals (CIs). The study protocol was registered in PROSPERO (ID: CRD420251102968).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 8 studies involving 64,235 patients were included in our analysis. Compared with morning dosing, bedtime dosing exhibited no significant differences in all-cause mortality (RR: 0.78; 95% CI: 0.59\u20131.04;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.09), major adverse cardiovascular events (RR: 0.80; 95% CI: 0.61\u20131.05;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.10) or cardiovascular death (RR: 0.59; 95% CI: 0.34\u20131.04;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.07). However, bedtime dosing significantly decreased heart failure risk (RR: 0.67; 95% CI: 0.46\u20130.96;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.03), lowered clinical systolic blood pressure (mean difference: \u22123.27\u00a0mmHg; 95% CI: \u22124.13 to \u22122.41;\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.00001), and improved non-dipper conversion (RR: 0.61; 95% CI: 0.47\u20130.77;\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.0001). Non-significant trends favoring bedtime dosing were noted for MI and coronary revascularization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>For critical outcomes, including MACE, all-cause mortality and cardiovascular death, no statistically significant benefits associated with bedtime dosing were observed. The overall findings are inconsistent, and the observed advantages for endpoints such as heart failure are closely linked to a single research group, necessitating cautious interpretation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251102968<\/jats:ext-link>\n                      , identifier CRD420251102968.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1758890","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:25:56Z","timestamp":1774848356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Timing of antihypertensive medication (bedtime versus morning) and cardiovascular risk: an updated systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Tuo","family":"Wang","sequence":"first","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijia","family":"Lai","sequence":"additional","affiliation":[{"name":"Geriatrics Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayang","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute of Cardiovascular Diseases, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xian","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute of Cardiovascular Diseases, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1097\/HJH.0000000000003508","article-title":"The effect of bedtime versus morning dosing of antihypertensive drugs on the cardiovascular outcomes: a systematic review and meta-analysis of randomized controlled trials","volume":"41","author":"Abuelazm","year":"2023","journal-title":"J. Hypertens."},{"key":"B2","doi-asserted-by":"publisher","first-page":"340","DOI":"10.3109\/07420528.2012.701455","article-title":"Cardiovascular risk of resistant hypertension: dependence on treatment-time regimen of blood pressure-lowering medications","volume":"30","author":"Ayala","year":"2013","journal-title":"Chronobiol Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1001\/jama.289.16.2073","article-title":"Principal results of the controlled onset verapamil investigation of cardiovascular end points (CONVINCE) trial","volume":"289","author":"Black","year":"2003","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1161\/HYPERTENSIONAHA.121.17356","article-title":"Missing verification of source data in hypertension research: the HYGIA PROJECT in perspective","volume":"78","author":"Brunstr\u00f6m","year":"2021","journal-title":"Hypertension"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1586\/erc.09.102","article-title":"INVEST revisited: review of findings from the international verapamil SR-Trandolapril study","volume":"7","author":"Cooper-DeHoff","year":"2009","journal-title":"Expert Rev. Cardiovasc Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"114045","DOI":"10.1016\/j.bcp.2020.114045","article-title":"Circadian rhythm in pharmacokinetics and its relevance to chronotherapy","volume":"178","author":"Dong","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1001\/jama.2025.4390","article-title":"Antihypertensive medication timing and cardiovascular events and death: the BedMed randomized clinical trial","volume":"333","author":"Garrison","year":"","journal-title":"JAMA"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e2513812","DOI":"10.1001\/jamanetworkopen.2025.13812","article-title":"Bedtime vs morning antihypertensive medications in frail older adults: the BedMed-Frail randomized clinical trial","volume":"8","author":"Garrison","year":"","journal-title":"JAMA Netw. Open"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.3109\/07420528.2010.510230","article-title":"Influence of circadian time of hypertension treatment on cardiovascular risk: results of the mapec study","volume":"27","author":"Hermida","year":"2010","journal-title":"Chronobiol Int."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4565","DOI":"10.1093\/eurheartj\/ehz754","article-title":"Bedtime hypertension treatment improves cardiovascular risk reduction: the hygia chronotherapy trial","volume":"41","author":"Hermida","year":"2020","journal-title":"Eur. Heart J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1161\/HYPERTENSIONAHA.114.04262","article-title":"Home blood pressure and cardiovascular outcomes in patients during antihypertensive therapy: primary results of HONEST, a large-scale prospective, real-world observational study","volume":"64","author":"Kario","year":"2014","journal-title":"Hypertens. Dallas Tex"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1161\/CIRCULATIONAHA.120.049730","article-title":"Nighttime blood pressure phenotype and cardiovascular prognosis: practitioner-based nationwide JAMP study","volume":"142","author":"Kario","year":"2020","journal-title":"Circulation"},{"key":"B13","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1097\/HJH.0000000000000371","article-title":"Evening versus morning dosing of antihypertensive drugs in hypertensive patients with sleep apnoea: a cross-over study","volume":"33","author":"Kasiakogias","year":"2015","journal-title":"J. Hypertens."},{"key":"B14","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1080\/08037051.2020.1747696","article-title":"Blood pressure medication should not be routinely dosed at bedtime. We must disregard the data from the HYGIA project","volume":"29","author":"Kreutz","year":"2020","journal-title":"Blood Press"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.61409\/v11230700","article-title":"Should antihypertensives be administrated at bedtime?","author":"Ladebo","year":"2024","journal-title":"Ugeskr. L\u00e6g."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1097\/HJH.0000000000003783","article-title":"Evening dosing versus morning dosing of antihypertensive medications for nocturnal hypertension: a systematic review and meta-analysis of 107 randomized controlled trials","volume":"42","author":"Lee","year":"2024","journal-title":"J. Hypertens."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4552","DOI":"10.1093\/eurheartj\/ehaa963","article-title":"Scientific integrity: what a journal can and cannot do","volume":"41","author":"L\u00fcscher","year":"2020","journal-title":"Eur. Heart J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1016\/S0140-6736(22)01786-X","article-title":"Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial","volume":"400","author":"Mackenzie","year":"2022","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1161\/HYPERTENSIONAHA.122.20862","article-title":"Timing of antihypertensive drug therapy: a systematic review and meta-analysis of randomized clinical trials","volume":"80","author":"Maqsood","year":"2023","journal-title":"Hypertens. Dallas Tex"},{"key":"B20","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.ophtha.2017.11.029","article-title":"Glaucomatous optic neuropathy associated with nocturnal dip in blood pressure: findings from the maracaibo aging study","volume":"125","author":"Melgarejo","year":"2018","journal-title":"Ophthalmology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/s0735-1097(98)00163-6","article-title":"Circadian blood pressure changes and myocardial ischemia in hypertensive patients with coronary artery disease","volume":"31","author":"Pierdomenico","year":"1998","journal-title":"J. Am. Coll. Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e621","DOI":"10.1111\/aos.12740","article-title":"Nocturnal blood pressure in primary open-angle glaucoma","volume":"93","author":"Pillunat","year":"2015","journal-title":"Acta Ophthalmol. (Copenh)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1126\/science.aax7621","article-title":"Dosing time matters","volume":"365","author":"Ruben","year":"2019","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1161\/hypertensionaha.115.06981","article-title":"Prognostic effect of the nocturnal blood pressure fall in hypertensive patients: the ambulatory blood pressure collaboration in patients with hypertension (ABC-H) meta-analysis","volume":"67","author":"Salles","year":"2016","journal-title":"Hypertens. Dallas Tex"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1016\/S0140-6736(23)00733-X","article-title":"Relationship between clinic and ambulatory blood pressure and mortality: an observational cohort study in 59 124 patients","volume":"401","author":"Staplin","year":"2023","journal-title":"Lancet Lond Engl."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1097\/HJH.0000000000003240","article-title":"Bedtime dosing of antihypertensive medications: systematic review and consensus statement: International society of hypertension position paper endorsed by world hypertension league and european society of hypertension","volume":"40","author":"Stergiou","year":"2022","journal-title":"J. Hypertens."},{"key":"B28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.2147\/IBPC.S223336","article-title":"Isolated nocturnal hypertension: what do we know and what can we do?","volume":"13","author":"Tadic","year":"2020","journal-title":"Integr. Blood Press Control"},{"key":"B29","doi-asserted-by":"publisher","first-page":"597","DOI":"10.2337\/diacare.21.4.597","article-title":"Outcome results of the fosinopril versus amlodipine cardiovascular events randomized trial (FACET) in patients with hypertension and NIDDM","volume":"21","author":"Tatti","year":"1998","journal-title":"Diabetes Care"},{"key":"B30","doi-asserted-by":"publisher","first-page":"01011-6","DOI":"10.1016\/j.cjca.2025.08.328","article-title":"Evening blood pressure medication administration and cardiovascular events: systematic review and meta-analysis","author":"Turgeon","year":"2025","journal-title":"Can. J. Cardiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/S1474-4422(07)70170-9","article-title":"Silent brain infarcts: a systematic review","volume":"6","author":"Vermeer","year":"2007","journal-title":"Lancet Neurol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"CD004184","DOI":"10.1002\/14651858.CD004184.pub3","article-title":"Evening versus morning dosing regimen drug therapy for hypertension","volume":"2024","author":"Wu","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1111\/ene.12659","article-title":"Reverse-dipper pattern of blood pressure May predict lacunar infarction in patients with essential hypertension","volume":"22","author":"Yan","year":"2015","journal-title":"Eur. J. Neurol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1758890\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:25:59Z","timestamp":1774848359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1758890\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":33,"alternative-id":["10.3389\/fphar.2026.1758890"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1758890","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"article-number":"1758890"}}