{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T17:15:27Z","timestamp":1785518127288,"version":"3.56.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100014337","name":"Menarini Group","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["High Blood Press Cardiovasc Prev"],"DOI":"10.1007\/s40292-026-00816-2","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:32:49Z","timestamp":1785515569000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of the Extemporaneous Combination Nebivolol\/Amlodipine in Patients with Hypertension Uncontrolled on Monotherapy: The BOTTICELLI Study"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9642-8380","authenticated-orcid":false,"given":"Massimo","family":"Volpe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-1271","authenticated-orcid":false,"given":"Giovambattista","family":"Desideri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6636-3080","authenticated-orcid":false,"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-1045","authenticated-orcid":false,"given":"Philippe","family":"Van De Borne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Baldini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3286-2479","authenticated-orcid":false,"given":"Suada","family":"Meto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fabrizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Melani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4237-6797","authenticated-orcid":false,"given":"Giorgio","family":"Reggiardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-3176","authenticated-orcid":false,"given":"Giuseppe","family":"Mancia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"4","key":"816_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41581-019-0244-2","volume":"16","author":"KT Mills","year":"2020","unstructured":"Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020;16(4):223\u201337. https:\/\/doi.org\/10.1038\/s41581-019-0244-2.","journal-title":"Nat Rev Nephrol"},{"key":"816_CR2","doi-asserted-by":"publisher","unstructured":"NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;398(10304):957-80. https:\/\/doi.org\/10.1016\/s0140-6736(21)01330-1.","DOI":"10.1016\/s0140-6736(21)01330-1"},{"issue":"33","key":"816_CR3","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","volume":"39","author":"B Williams","year":"2018","unstructured":"Williams B, Mancia G, Spiering W, et al. 2018 ESC\/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021\u2013104. https:\/\/doi.org\/10.1093\/eurheartj\/ehy339.","journal-title":"Eur Heart J"},{"issue":"8","key":"816_CR4","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1097\/hjh.0000000000001787","volume":"36","author":"C Thomopoulos","year":"2018","unstructured":"Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure-lowering treatment on cardiovascular outcomes and mortality: 13 - benefits and adverse events in older and younger patients with hypertension: overview, meta-analyses and meta-regression analyses of randomized trials. J Hypertens. 2018;36(8):1622\u201336. https:\/\/doi.org\/10.1097\/hjh.0000000000001787.","journal-title":"J Hypertens"},{"issue":"12","key":"816_CR5","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.1097\/hjh.0000000000003480","volume":"41","author":"G Mancia","year":"2023","unstructured":"Mancia G, Kreutz R, Brunstr\u00f6m M, et al. 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). J Hypertens. 2023;41(12):1874\u20132071. https:\/\/doi.org\/10.1097\/hjh.0000000000003480.","journal-title":"J Hypertens"},{"issue":"38","key":"816_CR6","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","volume":"45","author":"JW McEvoy","year":"2024","unstructured":"McEvoy JW, McCarthy CP, Bruno RM, et al. 2024 ESC guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45(38):3912\u20134018. https:\/\/doi.org\/10.1093\/eurheartj\/ehae178.","journal-title":"Eur Heart J"},{"key":"816_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107455","volume":"209","author":"G Grassi","year":"2024","unstructured":"Grassi G, Mancia G. Editorial - new European ESH and ESC guidelines for the management of hypertension: more similarities than differences. Pharmacol Res. 2024;209:107455. https:\/\/doi.org\/10.1016\/j.phrs.2024.107455.","journal-title":"Pharmacol Res"},{"issue":"17","key":"816_CR8","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1007\/s40265-018-0999-y","volume":"78","author":"AFG Cicero","year":"2018","unstructured":"Cicero AFG, Kuwabara M, Borghi C. A critical review of nebivolol and its fixed-dose combinations in the treatment of hypertension. Drugs. 2018;78(17):1783\u201390. https:\/\/doi.org\/10.1007\/s40265-018-0999-y.","journal-title":"Drugs"},{"issue":"1","key":"816_CR9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s40292-024-00687-5","volume":"32","author":"A Manolis","year":"2025","unstructured":"Manolis A, Karakasis P, Patoulias D, et al. Effect of nebivolol monotherapy or combination therapy on blood pressure levels in patients with hypertension: an updated systematic review and multilevel meta-analysis of 91 randomized controlled trials. High Blood Press Cardiovasc Prev. 2025;32(1):7\u201331. https:\/\/doi.org\/10.1007\/s40292-024-00687-5.","journal-title":"High Blood Press Cardiovasc Prev"},{"issue":"5 Suppl","key":"816_CR10","doi-asserted-by":"publisher","first-page":"S42","DOI":"10.1016\/j.cjca.2013.08.012","volume":"30","author":"TR Richards","year":"2014","unstructured":"Richards TR, Tobe SW. Combining other antihypertensive drugs with \u03b2-blockers in hypertension: a focus on safety and tolerability. Can J Cardiol. 2014;30(5 Suppl):S42\u20136. https:\/\/doi.org\/10.1016\/j.cjca.2013.08.012.","journal-title":"Can J Cardiol"},{"key":"816_CR11","doi-asserted-by":"publisher","first-page":"e24","DOI":"10.1016\/J.JASH.2015.03.058","volume":"9","author":"HA Punzi","year":"2015","unstructured":"Punzi HA. Combination therapy with nebivolol\/amlodipine is superior to metoprolol\/amlodipine in the control of cuff and 24-hr ambulatory blood pressure. J Am Soc Hypertens. 2015;9:e24. https:\/\/doi.org\/10.1016\/J.JASH.2015.03.058.","journal-title":"J Am Soc Hypertens"},{"issue":"1","key":"816_CR12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s43044-022-00254-0","volume":"74","author":"EM Sultan","year":"2022","unstructured":"Sultan EM, Rabea H, Elberry AA, Mahmoud HB. Effect of amlodipine\/nebivolol combination therapy on central BP and PWV compared to amlodipine\/valsartan combination therapy. Egypt Heart J. 2022;74(1):15. https:\/\/doi.org\/10.1186\/s43044-022-00254-0.","journal-title":"Egypt Heart J."},{"issue":"8","key":"816_CR13","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.2217\/fca-2021-0048","volume":"17","author":"C Ferri","year":"2021","unstructured":"Ferri C. The role of nebivolol in the management of hypertensive patients: from pharmacological profile to treatment guidelines. Future Cardiol. 2021;17(8):1421\u201333. https:\/\/doi.org\/10.2217\/fca-2021-0048.","journal-title":"Future Cardiol"},{"issue":"5","key":"816_CR14","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1007\/s10557-021-07205-y","volume":"36","author":"W AlHabeeb","year":"2022","unstructured":"AlHabeeb W, Mrabeti S, Abdelsalam AAI. Therapeutic properties of highly selective \u03b2-blockers with or without additional vasodilator properties: focus on bisoprolol and nebivolol in patients with cardiovascular disease. Cardiovasc Drugs Ther. 2022;36(5):959\u201371. https:\/\/doi.org\/10.1007\/s10557-021-07205-y.","journal-title":"Cardiovasc Drugs Ther"},{"key":"816_CR15","unstructured":"Electronic Medicines Compendium. Amlodipine. Summary of Product Characteristics 2023 [Available from: https:\/\/www.medicines.org.uk\/emc\/product\/4717\/smpc#gref."},{"issue":"12","key":"816_CR16","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1007\/s40265-015-0435-5","volume":"75","author":"J Fongemie","year":"2015","unstructured":"Fongemie J, Felix-Getzik E. A review of nebivolol pharmacology and clinical evidence. Drugs. 2015;75(12):1349\u201371. https:\/\/doi.org\/10.1007\/s40265-015-0435-5.","journal-title":"Drugs"},{"issue":"3","key":"816_CR17","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/j.1755-5922.2008.00054.x","volume":"26","author":"S Gupta","year":"2008","unstructured":"Gupta S, Wright HM. Nebivolol: a highly selective beta1-adrenergic receptor blocker that causes vasodilation by increasing nitric oxide. Cardiovasc Ther. 2008;26(3):189\u2013202. https:\/\/doi.org\/10.1111\/j.1755-5922.2008.00054.x.","journal-title":"Cardiovasc Ther"},{"issue":"1","key":"816_CR18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ijcard.2007.11.058","volume":"133","author":"KK Koh","year":"2009","unstructured":"Koh KK, Han SH, Ahn JY, Chung WJ, Lee Y, Shin EK. Amlodipine improves endothelial function and metabolic parameters in patients with hypertension. Int J Cardiol. 2009;133(1):23\u201331. https:\/\/doi.org\/10.1016\/j.ijcard.2007.11.058.","journal-title":"Int J Cardiol"},{"issue":"3","key":"816_CR19","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1097\/HJH.0000000000002296","volume":"38","author":"J Shin","year":"2020","unstructured":"Shin J, Choi YJ, Hong GR, et al. Real-world efficacy and safety of nebivolol in Korean patients with hypertension from the BENEFIT KOREA study. J Hypertens. 2020;38(3):527\u201335. https:\/\/doi.org\/10.1097\/HJH.0000000000002296.","journal-title":"J Hypertens"},{"issue":"5","key":"816_CR20","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1080\/03007995.2024.2328652","volume":"40","author":"G Desideri","year":"2024","unstructured":"Desideri G, Cipelli R, Pegoraro V, et al. Extemporaneous combination therapy with nebivolol\/amlodipine for the treatment of hypertension: a real-world evidence study in Europe. Curr Med Res Opin. 2024;40(5):733\u201343. https:\/\/doi.org\/10.1080\/03007995.2024.2328652.","journal-title":"Curr Med Res Opin"},{"key":"816_CR21","unstructured":"European Medicines Agency. Clinical investigation on medicinal products in the treatment of hypertension - Scientific guideline 2016 [Available from: https:\/\/www.ema.europa.eu\/en\/clinical-investigation-medicinal-products-treatment-hypertension-scientific-guideline."},{"issue":"2","key":"816_CR22","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1097\/jcma.0000000000000839","volume":"86","author":"SX Lu","year":"2023","unstructured":"Lu SX, Wu TW, Chou CL, Cheng CF, Wang LY. Combined effects of hypertension, hyperlipidemia, and diabetes mellitus on the presence and severity of carotid atherosclerosis in community-dwelling elders: a community-based study. J Chin Med Assoc. 2023;86(2):220\u20136. https:\/\/doi.org\/10.1097\/jcma.0000000000000839.","journal-title":"J Chin Med Assoc"},{"issue":"3","key":"816_CR23","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1111\/jch.13758","volume":"22","author":"HM Cheng","year":"2020","unstructured":"Cheng HM, Chuang SY, Wang TD, et al. Central blood pressure for the management of hypertension: is it a practical clinical tool in current practice? J Clin Hypertens (Greenwich). 2020;22(3):391\u2013406. https:\/\/doi.org\/10.1111\/jch.13758.","journal-title":"J Clin Hypertens (Greenwich)"},{"issue":"7","key":"816_CR24","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1080\/03007995.2022.2072087","volume":"38","author":"U Hostalek-Gottwald","year":"2022","unstructured":"Hostalek-Gottwald U, Gaciong Z. A growing evidence base for the fixed-dose combination of bisoprolol and amlodipine to manage hypertension. Curr Med Res Opin. 2022;38(7):1047\u201353. https:\/\/doi.org\/10.1080\/03007995.2022.2072087.","journal-title":"Curr Med Res Opin"},{"issue":"7","key":"816_CR25","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1080\/03007995.2023.2223915","volume":"39","author":"P J\u0119drusik","year":"2023","unstructured":"J\u0119drusik P, Placha G, Gaciong Z. Efficacy and safety of bisoprolol 5\u2009mg plus amlodipine 5\u2009mg in patients with hypertension uncontrolled on monotherapy with 5\u2009mg of amlodipine, a phase III multicenter, randomized, double-blind, placebo-controlled clinical trial - the AMCOR study. Curr Med Res Opin. 2023;39(7):939\u201346. https:\/\/doi.org\/10.1080\/03007995.2023.2223915.","journal-title":"Curr Med Res Opin"},{"issue":"5","key":"816_CR26","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.15062","volume":"13","author":"N Kumar","year":"2021","unstructured":"Kumar N, Khan SI, Versha F, et al. Comparison of effect of nebivolol and bisoprolol on sexual function of hypertensive female patients. Cureus. 2021;13(5):e15062. https:\/\/doi.org\/10.7759\/cureus.15062.","journal-title":"Cureus"},{"issue":"4","key":"816_CR27","first-page":"45","volume":"14","author":"II Simova","year":"2009","unstructured":"Simova II, Todorova-Konstantinova RR, Denchev SV. Effects of nebivolol versus bisoprolol on endothelial function in hypertensive patients. Exp Clin Cardiol. 2009;14(4):45\u20139.","journal-title":"Exp Clin Cardiol"},{"key":"816_CR28","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1080\/08038020410016548","volume":"1","author":"A Zanchetti","year":"2004","unstructured":"Zanchetti A. Clinical pharmacodynamics of nebivolol: new evidence of nitric oxide-mediated vasodilating activity and peculiar haemodynamic properties in hypertensive patients. Blood Press Suppl. 2004;1:17\u201332. https:\/\/doi.org\/10.1080\/08038020410016548.","journal-title":"Blood Press Suppl"},{"issue":"1","key":"816_CR29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2165\/11530710-000000000-00000","volume":"70","author":"O Kamp","year":"2010","unstructured":"Kamp O, Metra M, Bugatti S, et al. Nebivolol Drugs. 2010;70(1):41\u201356. https:\/\/doi.org\/10.2165\/11530710-000000000-00000.","journal-title":"Nebivolol. Drugs."},{"issue":"9","key":"816_CR30","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1111\/jch.14709","volume":"25","author":"JG Wang","year":"2023","unstructured":"Wang JG, Palmer BF, Anderson KV, Sever P. Amlodipine in the current management of hypertension. J Clin Hypertens. 2023;25(9):801\u20137. https:\/\/doi.org\/10.1111\/jch.14709.","journal-title":"J Clin Hypertens"}],"container-title":["High Blood Pressure & Cardiovascular Prevention"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40292-026-00816-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40292-026-00816-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40292-026-00816-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:32:51Z","timestamp":1785515571000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40292-026-00816-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":30,"alternative-id":["816"],"URL":"https:\/\/doi.org\/10.1007\/s40292-026-00816-2","relation":{},"ISSN":["1179-1985"],"issn-type":[{"value":"1179-1985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"17 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"MV has received honoraria for speakers\u2019 bureau or Advisory Boards from Astra Zeneca, Diasorin, GSK, Menarini Int, Neopharmed, Novartis, Pfizer, Polpharma, Sanofi, Sequirus, Servier. GD has received honoraria for speaking activities and advisory board participation from Menarini and Servier. RD has received honoraria and travel funding from Menarini. PVDB has received compensation for consultancy, advisory board, and speaker activities with Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, Menarini, Novartis, Novo Nordisk, and Sanofi, performed on behalf of ULB\u2013HUB Erasme Hospital (Brussels). GR declares to be a consultant for Menarini. GM, in the past 24 months, has received compensations as speaker\/chairman\/consultant from: Berlin Chemie, IPCA Laboratories, Medtronic Inc USA, Menarini Int, Merck Healthcare KGaA, Omnicuris, Recordati, Sanofi, Servier, Sun Laboratories. SB, SM, PF, LM declare to be employees of Menarini Group.","order":1,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the protocol, the recommendations on biomedical research on human patients of the Declaration of Helsinki, International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, EU-Directives and Regulations (applicable for the 2 countries), and national requirements of the participating countries. Approval was granted by the Republic of Bulgaria Ministry of Health Ethics Committee for Clinical Trials (20 April 2022, No. E\u041a\u041a\u0418\/CT 004) and by the Bioethics Committee at the District Medical Council of the Wielkopolska Medical Chamber in Pozna\u0144 (16 March 2022, No. 92\/2022), which acted as the Lead Committee for Poland, issuing a single opinion. Although local ethics committees retained the right to raise objections, no objections were raised by any local committee.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}