{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:23:48Z","timestamp":1787761428581,"version":"build-2784847793"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100011725","name":"Servier","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Adv Ther"],"DOI":"10.1007\/s12325-026-03765-3","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:50:39Z","timestamp":1787759439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Retrospective, Observational Study of Adherence, Persistence and Clinical Outcomes with Perindopril-Based Single-Pill or Free-Pill Antihypertensive Treatments in Italy"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4325-4932","authenticated-orcid":false,"given":"Ana Maria","family":"Vintila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-3686","authenticated-orcid":false,"given":"Stefano","family":"Masi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7020-6659","authenticated-orcid":false,"given":"Luca","family":"Degli Esposti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Dovizio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7598-8234","authenticated-orcid":false,"given":"Julien","family":"Magne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7777-7862","authenticated-orcid":false,"given":"Marta","family":"Nugnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2852-2022","authenticated-orcid":false,"given":"Chiara","family":"Veronesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3746-4506","authenticated-orcid":false,"given":"Jacek","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-0887","authenticated-orcid":false,"given":"Gianluigi","family":"Savarese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"11","key":"3765_CR1","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/s41569-021-00559-8","volume":"18","author":"B Zhou","year":"2021","unstructured":"Zhou B, Perel P, Mensah GA, Ezzati M. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol. 2021;18(11):785\u2013802.","journal-title":"Nat Rev Cardiol"},{"issue":"25","key":"3765_CR2","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","volume":"80","author":"M Vaduganathan","year":"2022","unstructured":"Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The global burden of cardiovascular diseases and risk: a compass for future health. J Am Coll Cardiol. 2022;80(25):2361\u201371.","journal-title":"J Am Coll Cardiol"},{"issue":"6","key":"3765_CR3","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1161\/CIRCULATIONAHA.115.018912","volume":"134","author":"KT Mills","year":"2016","unstructured":"Mills KT, Bundy JD, Kelly TN, et al. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016;134(6):441\u201350.","journal-title":"Circulation"},{"issue":"38","key":"3765_CR4","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.","journal-title":"Eur Heart J"},{"issue":"12","key":"3765_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, Brunstrom 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.","journal-title":"J Hypertens"},{"issue":"6","key":"3765_CR6","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1097\/HJH.0000000000002453","volume":"38","author":"T Unger","year":"2020","unstructured":"Unger T, Borghi C, Charchar F, et al. 2020 International Society of Hypertension global hypertension practice guidelines. J Hypertens. 2020;38(6):982\u20131004.","journal-title":"J Hypertens"},{"issue":"10304","key":"3765_CR7","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","volume":"398","author":"NCD Risk Factor Collaboration (NCD-RisC)","year":"2021","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\u201380.","journal-title":"Lancet."},{"issue":"3","key":"3765_CR8","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s40256-021-00505-6","volume":"22","author":"A Pathak","year":"2022","unstructured":"Pathak A, Poulter NR, Kavanagh M, Kreutz R, Burnier M. Improving the management of hypertension by tackling awareness, adherence, and clinical inertia: a symposium report. Am J Cardiovasc Drugs. 2022;22(3):251\u201361.","journal-title":"Am J Cardiovasc Drugs"},{"key":"3765_CR9","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.2147\/PPA.S368784","volume":"16","author":"SM Hamrahian","year":"2022","unstructured":"Hamrahian SM, Maarouf OH, Fulop T. A critical review of medication adherence in hypertension: barriers and facilitators clinicians should consider. Patient Prefer Adher. 2022;16:2749\u201357.","journal-title":"Patient Prefer Adher"},{"issue":"2","key":"3765_CR10","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1161\/HYPERTENSIONAHA.120.15781","volume":"77","author":"G Parati","year":"2021","unstructured":"Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to single-pill versus free-equivalent combination therapy in hypertension: a systematic review and meta-analysis. Hypertension. 2021;77(2):692\u2013705.","journal-title":"Hypertension"},{"issue":"1","key":"3765_CR11","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1097\/HJH.0000000000003570","volume":"42","author":"JR Snyman","year":"2024","unstructured":"Snyman JR, Bortolotto LA, Degli Esposti L, et al. A real-world analysis of outcomes and healthcare costs of patients on perindopril\/indapamide\/amlodipine single-pill vs. multiple-pill combination in Italy. J Hypertens. 2024;42(1):136\u201342.","journal-title":"J Hypertens"},{"issue":"4","key":"3765_CR12","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1007\/s12325-023-02451-y","volume":"40","author":"C Borghi","year":"2023","unstructured":"Borghi C, Jayagopal PB, Konradi A, et al. Adherence to triple single-pill combination of perindopril\/indapamide\/amlodipine: findings from real-world analysis in Italy. Adv Ther. 2023;40(4):1765\u201372.","journal-title":"Adv Ther"},{"issue":"9","key":"3765_CR13","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1097\/HJH.0000000000003497","volume":"41","author":"F Rea","year":"2023","unstructured":"Rea F, Morabito G, Savar\u00e9 L, Pathak A, Corrao G, Mancia G. Adherence and related cardiovascular outcomes to single pill vs. separate pill administration of antihypertensive triple-combination therapy. J Hypertens. 2023;41(9):1466\u201373.","journal-title":"J Hypertens"},{"issue":"11","key":"3765_CR14","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/hr.2017.65","volume":"40","author":"A Nehme","year":"2017","unstructured":"Nehme A, Zibara K. Efficiency and specificity of RAAS inhibitors in cardiovascular diseases: how to achieve better end-organ protection? Hypertens Res. 2017;40(11):903\u20139.","journal-title":"Hypertens Res"},{"issue":"15","key":"3765_CR15","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000010256","volume":"97","author":"X Lv","year":"2018","unstructured":"Lv X, Zhang Y, Niu Y, Song Q, Zhao Q. Comparison of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on cardiovascular outcomes in hypertensive patients with type 2 diabetes mellitus: a PRISMA-compliant systematic review and meta-analysis. Med (Baltimore). 2018;97(15):e0256.","journal-title":"Med (Baltimore)"},{"issue":"2","key":"3765_CR16","volume":"16","author":"TS Peresuodei","year":"2024","unstructured":"Peresuodei TS, Gill A, Orji C, Reghefaoui M, Saavedra Palacios MS, Nath TS. A comparative study of the safety and efficacy between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the management of hypertension: a systematic review. Cureus. 2024;16(2):e54311.","journal-title":"Cureus"},{"issue":"3","key":"3765_CR17","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1002\/pds.3935","volume":"25","author":"MJ Bijlsma","year":"2016","unstructured":"Bijlsma MJ, Janssen F, Hak E. Estimating time-varying drug adherence using electronic records: extending the proportion of days covered (PDC) method. Pharmacoepidemiol Drug Saf. 2016;25(3):325\u201332.","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"1","key":"3765_CR18","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1007\/s12325-023-02707-7","volume":"41","author":"S Masi","year":"2024","unstructured":"Masi S, Kobalava Z, Veronesi C, Giacomini E, Degli Esposti L, Tsioufis K. A retrospective observational real-world analysis of the adherence, healthcare resource consumption and costs in patients treated with bisoprolol\/perindopril as single-pill or free combination. Adv Ther. 2024;41(1):182\u201397.","journal-title":"Adv Ther"},{"issue":"8","key":"3765_CR19","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.1007\/s12325-024-02916-8","volume":"41","author":"L Perez de Isla","year":"2024","unstructured":"Perez de Isla L, Liberopoulos E, Dovizio M, Veronesi C, Degli Esposti L, Zambon A. Differential adherence to free and single-pill combination of rosuvastatin\/ezetimibe: findings from a real-world analysis in Italy. Adv Ther. 2024;41(8):3407\u201318.","journal-title":"Adv Ther"},{"key":"3765_CR20","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i3305","volume":"353","author":"Y Vinogradova","year":"2016","unstructured":"Vinogradova Y, Coupland C, Brindle P, Hippisley-Cox J. Discontinuation and restarting in patients on statin treatment: prospective open cohort study using a primary care database. BMJ. 2016;353:i3305.","journal-title":"BMJ"},{"key":"3765_CR21","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.2147\/PPA.S277676","volume":"14","author":"T Weiss","year":"2020","unstructured":"Weiss T, Carr RD, Pal S, et al. Real-world adherence and discontinuation of glucagon-like peptide-1 receptor agonists therapy in type 2 diabetes mellitus patients in the United States. Patient Prefer Adher. 2020;14:2337\u201345.","journal-title":"Patient Prefer Adher"},{"issue":"5","key":"3765_CR22","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373\u201383.","journal-title":"J Chronic Dis"},{"issue":"10","key":"3765_CR23","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1093\/ajh\/hpab083","volume":"34","author":"F Rea","year":"2021","unstructured":"Rea F, Savar\u00e9 L, Franchi M, Corrao G, Mancia G. Adherence to treatment by initial antihypertensive mono and combination therapies. Am J Hypertens. 2021;34(10):1083\u201391.","journal-title":"Am J Hypertens"},{"issue":"7","key":"3765_CR24","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1080\/14737167.2023.2293199","volume":"24","author":"AP Kengne","year":"2024","unstructured":"Kengne AP, Briere JB, Le Nouveau P, et al. Impact of single-pill combinations versus free-equivalent combinations on adherence and persistence in patients with hypertension and dyslipidemia: a systematic literature review and meta-analysis. Expert Rev Pharmacoecon Outcomes Res. 2024;24(7):817\u201327.","journal-title":"Expert Rev Pharmacoecon Outcomes Res"},{"issue":"5","key":"3765_CR25","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s40292-021-00465-7","volume":"28","author":"R Del Pinto","year":"2021","unstructured":"Del Pinto R, Desideri G, Ferri C, Agabiti Rosei E. Real-world antihypertensive treatment patterns, treatment adherence, and blood pressure control in the elderly: an Italian awareness-raising campaign on hypertension by Senior Italia FederAnziani, the Italian Society of Hypertension and the Italian Federation of General Practitioners. High Blood Press Cardiovasc Prev. 2021;28(5):457\u201366.","journal-title":"High Blood Press Cardiovasc Prev"},{"key":"3765_CR26","doi-asserted-by":"crossref","unstructured":"Campbell NRC, Paccot Burnens M, Whelton PK, et al. World Health Organization guideline on pharmacological treatment of hypertension: policy implications for the region of the Americas. Lancet Reg Health Am. 2022;9:None.","DOI":"10.1016\/j.lana.2022.100219"},{"issue":"11","key":"3765_CR27","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1097\/HJH.0000000000004111","volume":"43","author":"A Prejbisz","year":"2025","unstructured":"Prejbisz A, Dobrowolski P, Bozek G, Ko\u0144 B, et al. Patterns of prescription of antihypertensive medications in Poland: a one-year assessment of initiation and persistence of therapy in a nationwide population cohort. J Hypertens. 2025;43(11):1823\u201331.","journal-title":"J Hypertens"},{"issue":"3","key":"3765_CR28","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000258","volume":"83","author":"JB King","year":"2026","unstructured":"King JB, An J, Bellows BK, et al. Single-pill combination therapy for the management of hypertension: a scientific statement from the American Heart Association. Hypertension. 2026;83(3):e00258.","journal-title":"Hypertension"},{"issue":"12","key":"3765_CR29","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1097\/HJH.0000000000002598","volume":"38","author":"E Campana","year":"2020","unstructured":"Campana E, Cunha V, Glaveckaite S, et al. The use of single-pill combinations as first-line treatment for hypertension: translating guidelines into clinical practice. J Hypertens. 2020;38(12):2369\u201377.","journal-title":"J Hypertens"},{"issue":"3","key":"3765_CR30","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.jacc.2025.04.043","volume":"86","author":"DA Watkins","year":"2025","unstructured":"Watkins DA, Pickersgill SJ, Flood D, Gaziano TA, et al. Global impact of fixed-dose combination therapies on cardiovascular mortality and events, 2023\u20132050: a modeling study. J Am Coll Cardiol. 2025;86(3):149\u201361.","journal-title":"J Am Coll Cardiol"}],"container-title":["Advances in Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-026-03765-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12325-026-03765-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12325-026-03765-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:50:41Z","timestamp":1787759441000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12325-026-03765-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":30,"alternative-id":["3765"],"URL":"https:\/\/doi.org\/10.1007\/s12325-026-03765-3","relation":{},"ISSN":["0741-238X","1865-8652"],"issn-type":[{"value":"0741-238X","type":"print"},{"value":"1865-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"20 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ana Maria Vintila has received medical writing support, speaker fees, consultancy fees, and\/or support for transport from Amgen, Astra Zeneca, Berlin Chemie Menarini, Boehringer Ingelheim, KRKA, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Viatris, Vifor Pharma, Zentiva. S. Masi has received payments for consultancy, advisory board participation, speaking, and lecturing activities from Servier, which are related to the topic of this study. He also received honoraria from Servier for contributions to the study design and interpretation of results, for the current study. Julien Magne reports consulting fees from Servier. Jacek Wolf reports consulting fees and honoraria from Servier for lectures\/speaking activities, educational activities, and contributions to study design and results interpretation. He is immediate past president of the Polish Society of Hypertension (2022\u20132024). Gianluigi Savarese reports grants and consulting and personal fees from CSL Vifor, Boehringer Ingelheim, AstraZeneca, Servier, Novartis, Cytokinetics, Pharmacosmos, Medtronic, and Bayer, personal fees from Roche, Abbott, Edwards Lifescience, TEVA, Menarini, INTAS, GETZ, Laboratori Guidotti, Lupin, Atheneum, Genesis, Uppsala Clinical Research Center (UCR), Hikma, Medical Education Global Solutions, and Translational Medicine Academy Foundation, and grants from Boston Scientific, and Merck, all outside the submitted work. Marta Nugnes, Chiara Veronesi, Luca Degli Esposti and Melania Dovizio have nothing to disclose.","order":1,"name":"Ethics","label":"Conflict of Interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by all local ethics committees of participating LHUs (Supplementary material, Table\n                      \n                      ). The requirement to collect informed consent was waived, as it was considered unfeasible owing to organisational issues, in accordance with the \u2018Data Privacy Guarantor Authority, General Authorization for personal data treatment for scientific research purposes \u2013 n.9\/2014\u2019 and subsequent updates. This study was conducted in accordance with The Declaration of Helsinki, 1964, and its later amendments.","order":2,"name":"Ethics","label":"Ethical Approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}