{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:12:14Z","timestamp":1791378734752,"version":"4.3.2"},"reference-count":34,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Arterial hypertension (HT) is one of the most prevalent diseases, causing increased morbidity and mortality. Treatment of HT might be complicated by multiple drug intolerance syndrome (MDIS), defined as intolerance to three or more drug classes. This systematic review and meta-analysis aimed to assess the prevalence of MDIS in patients with hypertension and investigate its impact on disease control. Materials and Methods: MEDLINE, Scopus, Web of Science, and Embase were thoroughly searched in June 2024. The data concerning MDIS prevalence, MDIS risk factors, number of adverse drug reactions (ADRs), and types of reactions was extracted. Quality assessment was done with the use of the Newcastle-Ottawa Scale. Meta-analysis was conducted to determine the pooled prevalence of MDIS and ADRs. The study was conducted according to the PRISMA guidelines. Results: This review included four studies (2508 patients). The pooled prevalence of MDIS was 10% (95% CI: 4%\u201319%). Headache was the most frequent ADR reported in the studies (71.47%, 95% CI: 56.5%\u201384.44%), while pain in other body parts was present in 53.08% of patients. Female sex was found to increase the risk of MDIS in each included study. Other risk factors identified were older age, gastrointestinal disorders, anxiety disorders, panic attacks, and depression. Blood pressure was higher in the MDIS group, and in this group, more patients had uncontrolled hypertension. Conclusions: The prevalence of MDIS in the hypertensive population can be considered high. Furthermore, blood pressure control is worse in patients with MDIS. However, this phenomenon is still studied inadequately, and further research is necessary.<\/jats:p>","DOI":"10.3390\/jcm14176218","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T15:15:57Z","timestamp":1756912557000},"page":"6218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiple Drug Intolerance Syndrome and Arterial Hypertension\u2014Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Jakub","family":"Rusinek","sequence":"first","affiliation":[{"name":"Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, 31-538 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9505-765X","authenticated-orcid":false,"given":"Kinga","family":"Tyjas","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, Jakubowskiego St. 2, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2766-4819","authenticated-orcid":false,"given":"Wiktoria","family":"Zi\u00f3\u0142ek","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Group at the 1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Rajzer","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, Jakubowskiego St. 2, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7057-7302","authenticated-orcid":false,"given":"Katarzyna","family":"Stolarz-Skrzypek","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, Jakubowskiego St. 2, 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2023). Global Report on Hypertension, WHO."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/S0140-6736(02)11911-8","article-title":"Age-specific relevance of usual blood pressure to vascular mortality: A meta-analysis of individual data for one million adults in 61 prospective studies","volume":"360","author":"Lewington","year":"2002","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.pharmthera.2005.09.002","article-title":"Mechanisms of target organ damage caused by hypertension: Therapeutic potential","volume":"111","author":"Cohuet","year":"2006","journal-title":"Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC Guidelines for the management of elevated blood pressure and hypertension: Developed by the task force on the management of elevated blood pressure and hypertension of the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO)","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Insani, W.N., Whittlesea, C., Alwafi, H., Man, K.K.C., Chapman, S., and Wei, L. (2021). Prevalence of adverse drug reactions in the primary care setting: A systematic review and meta-analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252161"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ejim.2024.04.011","article-title":"Single-pill combination for treatment of hypertension: Just a matter of practicality or is there a real clinical benefit?","volume":"126","author":"Coca","year":"2024","journal-title":"Eur. J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.anai.2011.11.006","article-title":"Multiple drug intolerance syndrome: Prevalence, clinical characteristics, and management","volume":"108","author":"Macy","year":"2012","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2174\/1574884713666181112125714","article-title":"Multiple Drug Intolerance Syndrome: An Underreported Distinct Clinical Entity","volume":"14","author":"Behera","year":"2018","journal-title":"Curr. Clin. Pharmacol."},{"key":"ref_9","first-page":"16399","article-title":"Multiple drug intolerance in patients with arterial hypertension: Prevalence and determining factors","volume":"133","author":"Polaczyk","year":"2023","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_10","first-page":"e123","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement","volume":"3","author":"Moher","year":"2009","journal-title":"Open Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1097\/HJH.0000000000003737","article-title":"Multiple drug intolerance in antihypertensive patients: What is known and what is missing","volume":"42","author":"Palermiti","year":"2024","journal-title":"J. Hypertens."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1001\/archinte.163.5.592","article-title":"Drug intolerance due to nonspecific adverse effects related to psychiatric morbidity in hypertensive patients","volume":"163","author":"Davies","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"ref_13","unstructured":"Wells, G., Shea, B., O\u2019Connell, D., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2024, November 10). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses 2021. Available online: https:\/\/www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1177\/2042098617705625","article-title":"Multidrug intolerance in the treatment of hypertension: Result from an audit of a specialized hypertension service","volume":"8","author":"Okeahialam","year":"2017","journal-title":"Ther. Adv. Drug Saf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/jch.12637","article-title":"Management of Hypertensive Patients with Multiple Drug Intolerances: A Single-Center Experience of a Novel Treatment Algorithm","volume":"18","author":"Antoniou","year":"2016","journal-title":"J. Clin. Hypertens."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e12190","DOI":"10.1002\/clt2.12190","article-title":"Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: A systematic review","volume":"12","author":"Jagpal","year":"2022","journal-title":"Clin. Transl. Allergy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1111\/all.13440","article-title":"Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression","volume":"73","author":"Blumenthal","year":"2018","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s40264-014-0236-x","article-title":"Multiple Drug Intolerance Syndrome: A Large-Scale Retrospective Study","volume":"37","author":"Omer","year":"2014","journal-title":"Drug Saf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.33963\/KP.a2022.0232","article-title":"The occurrence of drug-induced side effects in women and men with arterial hypertension and comorbidities","volume":"80","author":"Polaczyk","year":"2022","journal-title":"Kardiol. Pol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2165\/00002018-200831060-00006","article-title":"Adverse drug reaction reporting by patients in the Netherlands: Three years of experience","volume":"31","author":"Passier","year":"2008","journal-title":"Drug Saf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10194-009-0127-1","article-title":"Focus on headache as an adverse reaction to drugs","volume":"10","author":"Ferrari","year":"2009","journal-title":"J. Headache Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"310","DOI":"10.3109\/15360288.2012.736933","article-title":"Chronic diseases in the European Union: The prevalence and health cost implications of chronic pain","volume":"26","author":"Leadley","year":"2012","journal-title":"J. Pain Palliat. Care Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1751-7176.2011.00512.x","article-title":"Thiazide and loop diuretics","volume":"13","author":"Sica","year":"2011","journal-title":"J. Clin. Hypertens."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Na Takuathung, M., Sakuludomkan, W., Khatsri, R., Dukaew, N., Kraivisitkul, N., Ahmadmusa, B., Mahakkanukrauh, C., Wangthaweesap, K., Onin, J., and Srichai, S. (2022). Adverse Effects of Angiotensin-Converting Enzyme Inhibitors in Humans: A Systematic Review and Meta-Analysis of 378 Randomized Controlled Trials. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19148373"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"n189","DOI":"10.1136\/bmj.n189","article-title":"Association between antihypertensive treatment and adverse events: Systematic review and meta-analysis","volume":"372","author":"Albasri","year":"2021","journal-title":"BMJ"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1111\/all.12881","article-title":"Drug allergies documented in electronic health records of a large healthcare system","volume":"71","author":"Zhou","year":"2016","journal-title":"Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11739-011-0510-1","article-title":"Allergy and psychologic evaluations of patients with multiple drug intolerance syndrome","volume":"7","author":"Nucera","year":"2012","journal-title":"Intern. Emerg. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1097\/HJH.0000000000000901","article-title":"Changes in hypertension prevalence, awareness, treatment, and control rates in Turkey from 2003 to 2012","volume":"34","author":"Sengul","year":"2016","journal-title":"J. Hypertens."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1097\/HJH.0000000000001572","article-title":"Perspectives on hypertension\u2019s prevalence, treatment and control in a high cardiovascular risk East European country: Data from the SEPHAR III survey","volume":"36","author":"Dorobantu","year":"2018","journal-title":"J. Hypertens."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/HJH.0b013e32834d30ec","article-title":"Control of arterial hypertension in Spain: A systematic review and meta-analysis of 76 epidemiological studies on 341 632 participants","volume":"30","author":"Ridao","year":"2012","journal-title":"J. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/jch.14653","article-title":"Comprehensive effects of lifestyle reform, adherence, and related factors on hypertension control: A review","volume":"25","author":"Ojangba","year":"2023","journal-title":"J. Clin. Hypertens."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/MAJ.0000000000000298","article-title":"Comprehensive approach for hypertension control in low-income populations: Rationale and study design for the hypertension control program in argentina","volume":"348","author":"Mills","year":"2014","journal-title":"Am. J. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2940","DOI":"10.1093\/eurheartj\/eht295","article-title":"Adherence to cardiovascular therapy: A meta-analysis of prevalence and clinical consequences","volume":"34","author":"Chowdhury","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/bcp.14417","article-title":"Prevalence of adverse drug events and adverse drug reactions in hospital among older patients with dementia: A systematic review","volume":"87","author":"Sakiris","year":"2021","journal-title":"Br. J. Clin. Pharmacol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/17\/6218\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:38:30Z","timestamp":1760035110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/17\/6218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":34,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["jcm14176218"],"URL":"https:\/\/doi.org\/10.3390\/jcm14176218","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]}}}