{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:56:08Z","timestamp":1791348968647,"version":"4.3.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertension is a major modifiable risk factor for cardiovascular disease, yet global control rates remain low. Zilebesiran, an investigational RNA interference therapy, targets angiotensinogen to modulate the renin\u2013angiotensin\u2013aldosterone system. While previous reviews exist, updated evidence is needed to better characterize its efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of PubMed, Cochrane Library, Google Scholar, Embase, and ClinicalTrials.gov was conducted using MeSH and free-text terms. Two reviewers independently extracted data and assessed risk of bias using RoB 2.0. A random-effects model was applied in RevMan 5.4, with heterogeneity evaluated using I\u00b2 statistics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Four studies involving 1,412 adults with mild to moderate hypertension were included. The primary outcome, placebo-adjusted change in office systolic blood pressure (SBP), showed a pooled mean difference (MD) of \u22127.16 mmHg (95% CI: \u221213.63 to \u22120.70). Secondary outcomes demonstrated significant reductions in 24-hour ambulatory SBP (MD: \u22129.92 mmHg; 95% CI: \u221218.74 to \u22121.10), daytime SBP (MD: \u22129.76 mmHg; 95% CI: \u221219.46 to \u22120.06), nighttime SBP (MD: \u22129.95 mmHg; 95% CI: \u221216.71 to \u22123.19), and 24-hour ambulatory diastolic blood pressure (DBP) (MD: \u22127.27 mmHg; 95% CI: \u221211.13 to \u22123.41). In subgroup analysis by follow-up duration, the reduction in daytime SBP was significantly greater at 3 months than at 6 months (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.02), suggesting a potential attenuation of the antihypertensive effect over time. Zilebesiran markedly reduced angiotensinogen levels (MD: \u22121.00; 95% CI: \u22121.15 to \u22120.85). Overall adverse events were significantly more frequent with Zilebesiran compared with placebo (OR: 1.46), including increased risks of hyperkalemia and injection-site reactions, while serious adverse events did not differ significantly between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, zilebesiran produced significant and consistent BP reductions, especially in ambulatory measures, with a favorable safety profile. However, evidence remains limited by small sample sizes and reliance on placebo comparators, and larger trials with active antihypertensive controls are needed to validate long-term efficacy and safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00228-026-04179-4","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:07:04Z","timestamp":1789531624000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of zilebesiran in adults with hypertension: a systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.1007","volume":"82","author":[{"given":"Muhammad","family":"Hussain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asharib","family":"Sohaib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saifullah","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Hannan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan Abdul Aziz","family":"Dhedhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Naz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameer Haider","family":"Cheema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faizan","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"#cr-split#-4179_CR1.1","unstructured":"Vemu PL, Yang E, Ebinger J (2023) ESH Hypertension Guideline Update: Bringing Us Closer Together Across the Pond [Internet]. 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