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We conducted an individual participant-level data meta-analysis of 51 randomized trials from the Blood Pressure Lowering Treatment Trialists\u02bc Collaboration (358,642 participants; median follow-up: 4.2\u2009years). Using Cox proportional hazards models, we estimated time-stratified hazard ratios (HRs) for major cardiovascular events (MACE; fatal or non-fatal stroke, ischemic heart disease or heart failure) across annual follow-up intervals up to more than 5\u2009years, standardized to a 5-mmHg systolic BP reduction. Network meta-analysis examined whether temporal patterns differed across antihypertensive drug classes. Annual MACE incidence was highest during year 1 (3.0% treatment versus 3.6% control), declined during years 1\u22125 and then rose at more than 5\u2009years (3.1% versus 3.4%). BP lowering reduced MACE risk, with benefits established early and not progressively increasing over time. A 5-mmHg systolic BP reduction was associated with a 12% lower MACE risk in year 1 (HR\u2009=\u20090.88, 95% confidence interval (CI): 0.84\u22120.91), with modest attenuation thereafter: HRs were 0.88 (0.85\u22120.92) in years 1\u22122, 0.94 (0.90\u22120.98) in years 2\u22123, 0.87 (0.83\u22120.92) in years 3\u22124, 0.97 (0.91\u20131.03) in years 4\u22125 and 0.94 (0.87\u22121.01) at more than 5\u2009years (\n                    <jats:italic>P<\/jats:italic>\n                    for trend\u2009=\u20090.006). Similar patterns occurred across five drug classes. These findings indicate that the relative cardiovascular benefits of BP lowering emerge within months and do not increase over time, suggesting that prioritizing higher-risk individuals for treatment yields greater clinical utility than prolonged treatment in low-risk individuals.\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04514-3","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:29:03Z","timestamp":1782912543000},"page":"3082-3092","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A meta-analysis of the long-term effects of antihypertensive therapy on the risk of major cardiovascular disease across 51 randomized trials"],"prefix":"10.1038","volume":"32","author":[{"given":"Qianqian","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Bidel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexter","family":"Canoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guyu","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Cushman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rodgers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koon","family":"Teo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry R.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9931-0580","authenticated-orcid":false,"given":"John","family":"Chalmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6011-681X","authenticated-orcid":false,"given":"Carl J.","family":"Pepine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-8454","authenticated-orcid":false,"given":"Johan","family":"Sundstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9800-5296","authenticated-orcid":false,"given":"Mark","family":"Woodward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-8874","authenticated-orcid":false,"given":"Milad","family":"Nazarzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-4610","authenticated-orcid":false,"given":"Kazem","family":"Rahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"4514_CR1","doi-asserted-by":"publisher","first-page":"e261","DOI":"10.1016\/S2468-2667(24)00018-5","volume":"9","author":"C Wagner","year":"2024","unstructured":"Wagner, C. et al. 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Med."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04514-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04514-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04514-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T22:01:45Z","timestamp":1786658505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04514-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":46,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["4514"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04514-3","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"assertion":[{"value":"16 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors have completed the International Committee of Medical Journal Editors (ICMJE) uniform disclosure form at\n                      \n                      and declare the following competing interests. K.R. has received grants outside the submitted work from the British Heart Foundation, the Horizon Europe AI4HF consortium (grant R79992\/CN001), the Novo Nordisk Oxford Big Data Partnership, the University of Oxford and the UK Research and Innovation Global Challenge Research Fund (grant ES\/P011055\/1); has received consulting fees from Medtronic CRDN; has received honoraria or fees from\n                      Heart\n                      ,\n                      PLoS Medicine\n                      , AstraZeneca MEA Region, Medscape and WebMD Medscape UK; and is the editor-in-chief of\n                      Heart\n                      . Q.Y. has received scholarship support from the China Scholarship Council\u2212University of Oxford Scholarships and the China Oxford Scholarship Fund. M.N. is supported by an individual research fellowship from the British Heart Foundation (grant FS\/IPBSRF\/22\/27060) and has received reimbursement and honoraria from AstraZeneca, Nemysis, Albus Health and BMJ Publishing Group (as statistical adviser of\n                      Heart\n                      ) outside the submitted work. Z.B. has received a PhD fellowship from the British Heart Foundation (FS\/PhD\/25\/29632). D.C. has received support from the UK Research and Innovation Medical Research Council (MR\/Y010825\/1), the Vivensa Foundation (formerly Dunhill Medical Trust) (ARVHF2402\/7) and the National Institute for Health and Care Research (NIR203982) outside the submitted work; the views expressed are not necessarily those of these funders. D.C. has also received an honorarium as Specialty Chief Editor of\n                      Frontiers in Cardiovascular Medicine\n                      (\n                      Cardiovascular Epidemiology and Prevention\n                      ). J.C. has received grants from the National Health and Medical Research Council of Australia for work unrelated to this submission. M.W. has received personal fees from Amgen, Kyowa Kirin and Freeline. C.J.P. received grants outside the submitted work from the NHLBI (R01-MPI; Angiotensin, resistant hypertension and microbiota), the US Department of Defence (WARRIOR and QUIET WARRIOR W81XWH-17-2-0030), University of Florida Health, the McJunkin Family Charitable Foundation Trust and the Gatorade Trust. All payments were to the University of Florida. C.J.P. has also received honoraria from Elsevier as the Editor-in-Chief of\n                      American Heart Journal Plus\n                      . W.C.C. has received consulting fees from Alnylam, Idorsia and Azurity Pharmaceuticals and a grant from George Medicines. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}