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We aimed to identify potential ACEI\u2010induced PCs using high\u2010throughput sequence symmetry analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using claims data from a national sample of Medicare beneficiaries (2011\u20132020), we identified new ACEI users aged \u2265\u200966\u2009years with continuous enrollment \u2265\u2009360\u2009days before and \u2265\u2009180\u2009days after ACEI initiation. We screened for initiation of 446 other (non\u2010antihypertensive) \u201cmarker\u201d drug classes within \u00b190\u2009days of ACEI initiation, generating sequence ratios (SRs) reflecting proportions of ACEI users starting the marker class after versus before ACEI initiation. Adjusted SRs (aSRs) accounted for prescribing trends over time. For significant aSRs, we calculated the naturalistic number needed to harm (NNTH), and significant signals underwent clinical review for plausibility.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 308\u2009579 ACEI initiators (mean age 76.1\u2009\u00b1\u20097.5\u2009years; 59.6% female; 88.6% with hypertension). Of 446 marker classes evaluated, 81 signals were significant, and 42 (52%) classified as potential PCs after clinical review. The strongest signals ranked by lowest NNTH included corticosteroids (NNTH 313; 95% CI, 262\u2013392) and serotonin type 3 (5\u2010HT<jats:sub>3<\/jats:sub>) antagonists (NNTH 496; 95% CI, 392\u2013689); the strongest signals ranked by highest aSR included sympathomimetics (aSR, 1.97; 95% CI, 1.10\u20133.53) and other antianemic preparations (aSR, 1.87; 95% CI, 1.31\u20132.67).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Identified prescribing cascade signals were indicative of known and possibly underrecognized ACEI adverse events in this Medicare cohort. The findings are hypothesis\u2010generating and require further investigation to determine the extent and impact of the identified PCs on health outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.70132","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T05:40:07Z","timestamp":1742276407000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["High\u2010Throughput Screening for Prescribing Cascades Among Real\u2010World Angiotensin\u2010Converting Enzyme Inhibitor Initiators"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-3915","authenticated-orcid":false,"given":"Asinamai M.","family":"Ndai","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy, College of Pharmacy University of Florida  Gainesville Florida USA"},{"name":"Center for Integrative Cardiovascular and Metabolic Disease University of Florida  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