{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:42:45Z","timestamp":1792208565405,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    Concomitant congestive heart failure (CHF) and diabetes mellitus (DM) patients frequently are treated with polypharmacy, thus potentially increasing the risk of drug\u2013drug interactions (pDDIs). Conventional DDI screening methods often fail to distinguish clinically significant interactions from recommended therapeutic combinations. This study assessed the prevalence, severity, and clinical consequences of pDDIs in hospitalized patients with CHF and DM. This ambispective, cross\u2010sectional study included 144 hospitalized patients with CHF and DM. We used the Micromedex and Lexicomp databases to check prescriptions. We classified clinically relevant DDIs and therapeutic combinations requiring routine monitoring by severity. 207 pDDIs were identified, of which 84.1% were moderate and 15.9% severe. Polypharmacy was a major risk factor for the DDI burden, and over seven drugs were associated with significantly more interactions than fewer drugs (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Polypharmacy was an independent predictor of clinically significant DDI (AOR 3.42; 95% CI 1.78\u20136.59) in the multivariate analysis. The most commonly seen combinations (statin\u2013ezetimibe and sulfonylurea\u2013metformin therapy) are guideline\u2010recommended and do not need to be avoided. Clinical pharmacists and prescribing clinicians performing context\u2010aware interpretation of DDI alerts by differentiating between guideline\u2010recommended therapeutic combinations requiring monitoring and truly actionable interactions can reduce alert fatigue, preserve evidence\u2010based therapy, and support safe prescribing in complex CHF\u2010DM patients.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70528","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:37:13Z","timestamp":1792208233000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug\u2013Drug Interactions vs. Therapeutic Combinations in Patients with Congestive Heart Failure and Diabetes: An Ambispective Real\u2010World Study"],"prefix":"10.1002","author":[{"given":"Navakanth Raju","family":"Ramayanam","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy Dr. M.G.R. Educational and Research Institute  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhawarlal","family":"Kavitha","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Dr. M.G.R. Educational and Research Institute  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitthi Babu","family":"Prathisha","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Dr. M.G.R. Educational and Research Institute  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharmaraj","family":"Samundeeswary","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Dr. M.G.R. Educational and Research Institute  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharath Kumar Mamilla","family":"Mugaiahgari","sequence":"additional","affiliation":[{"name":"Department of Emergency Medical Services, College of Applied Medical Sciences King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayapa Reddy","family":"Narapureddy","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Applied Medical Sciences King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-2953","authenticated-orcid":false,"given":"Sarad Pawar Naik","family":"Bukke","sequence":"additional","affiliation":[{"name":"Department of Pharmacy \u2013 Faculty of Health Sciences Victoria University  Kampala Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_16_1_1","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in patients with heart failure and reduced ejection fraction","volume":"381","author":"McMurray J.J.V.","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"e_1_2_16_2_1","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1093\/eurheartj\/ehz835","article-title":"Sex differences in heart failure","volume":"40","author":"Lam C.S.P.","year":"2019","journal-title":"Eur. Heart J."},{"issue":"1","key":"e_1_2_16_3_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.2337\/dc24-SINT","article-title":"Standards of Care in Diabetes\u20142024","volume":"47","author":"American Diabetes Association","year":"2024","journal-title":"Diabetes Care"},{"key":"e_1_2_16_4_1","doi-asserted-by":"crossref","first-page":"e263","DOI":"10.1016\/j.jacc.2021.12.012","article-title":"2022 AHA\/ACC\/HFSA guideline for the Management of Heart Failure: a report of the American College of Cardiology\/American Heart Association joint committee on clinical practice guidelines","volume":"79","author":"Heidenreich P.A.","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"e_1_2_16_5_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1517\/14740338.2013.827660","article-title":"Clinical consequences of polypharmacy in elderly","volume":"13","author":"Maher R.L.","year":"2014","journal-title":"Expert Opin. Drug Saf."},{"key":"e_1_2_16_6_1","doi-asserted-by":"crossref","DOI":"10.1093\/ageing\/afaf233","article-title":"Longitudinal trajectories of polypharmacy in older people, and their association with the risk of mortality: a joint latent class model analysis of real\u2010world data from the UK and The Netherlands","volume":"54","author":"Elhussein L.","year":"2025","journal-title":"Age Ageing"},{"key":"e_1_2_16_7_1","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.120.006977","article-title":"Polypharmacy in older adults hospitalized for heart failure","volume":"13","author":"Unlu O.","year":"2020","journal-title":"Circ. Heart Fail."},{"key":"e_1_2_16_8_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/ehjcvp\/pvac005","article-title":"Facing the challenge of polypharmacy when prescribing for older people with cardiovascular disease. A review by the European Society of Cardiology Working Group on cardiovascular pharmacotherapy","volume":"8","author":"Tamargo J.","year":"2022","journal-title":"Eur. Heart J. Cardiovasc. Pharmacother."},{"key":"e_1_2_16_9_1","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1002\/pds.5691","article-title":"A meta\u2010analysis assessing the prevalence of drug\u2010drug interactions among hospitalized patients","volume":"32","author":"Aksoy N.","year":"2023","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"e_1_2_16_10_1","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s40266-021-00898-8","article-title":"Prevalence and factors associated with potential drug\u2010drug interactions in older community\u2010dwelling adults: a prospective cohort study","volume":"38","author":"Hughes J.E.","year":"2021","journal-title":"Drugs Aging"},{"key":"e_1_2_16_11_1","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.3390\/pharmaceutics16091137","article-title":"Drug\u2010drug interactions in nosocomial infections: an updated review for clinicians","volume":"16","author":"H\u00eencu S.","year":"2024","journal-title":"Pharmaceutics"},{"key":"e_1_2_16_12_1","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s00228-022-03292-4","article-title":"Drug interaction alerts in older primary care patients, and related medically justified actions","volume":"78","author":"Tukukino C.","year":"2022","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"e_1_2_16_13_1","doi-asserted-by":"crossref","DOI":"10.1177\/14604582221100678","article-title":"Prescribers' reported acceptance and use of drug\u2010drug interaction alerts: an Australian survey","volume":"28","author":"Baysari M.T.","year":"2022","journal-title":"Health Informatics J."},{"key":"e_1_2_16_14_1","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1093\/jamia\/ocaf139","article-title":"Effect of electronic drug\u2010drug interaction alerts on patient and clinician outcomes: a systematic review","volume":"32","author":"Holbrook A.M.","year":"2025","journal-title":"J. Am. Med. Inform. Assoc."},{"key":"e_1_2_16_15_1","first-page":"844","article-title":"In pursuit of the alert fatigue: an assessment of drug alert burden at a large academic medical center","volume":"2024","author":"Masud J.H.B.","year":"2024","journal-title":"AMIA Annu. Symp. Proc. AMIA Symp"},{"key":"e_1_2_16_16_1","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/jamia\/ocz095","article-title":"Medication safety alert fatigue may be reduced via interaction design and clinical role tailoring: a systematic review","volume":"26","author":"Hussain M.I.","year":"2019","journal-title":"J. Am. Med. Inform. Assoc."},{"key":"e_1_2_16_17_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1136\/amiajnl-2012-001089","article-title":"Drug\u2010drug interactions that should be non\u2010interruptive in order to reduce alert fatigue in electronic health records","volume":"20","author":"Phansalkar S.","year":"2013","journal-title":"J. Am. Med. Inform. Assoc."},{"key":"e_1_2_16_18_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.26442\/20751753.2020.5.200198","article-title":"Management of patients with chronic heart failure and diabetes mellitus from the standpoint of modern recommendations and in real clinical practice","volume":"22","author":"Pirogov Russian National Research Medical University, Moscow, Russia","year":"2020","journal-title":"Cons. Med."},{"key":"e_1_2_16_19_1","doi-asserted-by":"crossref","DOI":"10.31083\/j.rcm2512436","article-title":"Diabetes mellitus and cardiovascular disease: exploring epidemiology, pathophysiology, and treatment strategies","volume":"25","author":"Siam N.H.","year":"2024","journal-title":"Rev. Cardiovasc. Med."},{"key":"e_1_2_16_20_1","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1093\/eurheartj\/ehad192","article-title":"2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes","volume":"44","author":"Marx N.","year":"2023","journal-title":"Eur. Heart J."},{"key":"e_1_2_16_21_1","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/cpt.2624","article-title":"Contextualized drug\u2010drug interaction management improves clinical utility compared with basic drug\u2010drug interaction Management in Hospitalized Patients","volume":"112","author":"Wasylewicz A.T.M.","year":"2022","journal-title":"Clin. Pharmacol. 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Sci."},{"key":"e_1_2_16_25_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.12997\/jla.2021.10.3.303","article-title":"Combination of statin and ezetimibe versus statin monotherapy on cardiovascular disease and type 2 diabetes incidence among adults with impaired fasting glucose: a propensity\u2010matched Nationwide cohort study","volume":"10","author":"Lee Y.\u2010B.","year":"2021","journal-title":"J. Lipid Atheroscler."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70528","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70528","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:37:18Z","timestamp":1792208238000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":25,"alternative-id":["10.1002\/cpt.70528"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70528","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"2026-07-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70528"}}