{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T11:05:51Z","timestamp":1779534351574,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,20]]},"group-title":"Cardiovascular Medicine","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Dihydropyridine calcium channel blockers (DHP-CCB) are widely prescribed antihypertensives whose adverse effects may trigger unnecessary prescribing of additional medications, termed prescribing cascades (PC). We aimed to identify potential DHP-CCB-induced PCs using high-throughput sequence symmetry analysis (HTSSA).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using Medicare claims data (2011-2020), we identified new users aged \u226566 years with continuous enrollment \u2265360 days before and \u2265180 days after DHP-CCB initiation. We screened for initiation of 446 \u201cmarker\u201d drug classes within \u00b190 days of DHP-CCB initiation. Sequence ratios compared marker drug initiation after versus before DHP-CCB initiation. Adjusted sequence ratios (aSR), accounting for prescribing trends over time, were calculated with 95% CIs &gt;1 considered statistically significant. Clinical experts classified statistically significant signals as potential PCs through consensus.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 388,862 DHP-CCB initiators (mean age 76.6 \u00b1 7.5 years; 62.5% women, 92.3% with hypertension), 82 of 446 marker drug classes had significantly elevated aSRs, of which 24 were classified as potential PCs. Strongest signals ranked by highest aSR included other systemic hemostatics (aSR 2.99; 95% CI, 1.10-8.16), other nasal preparations (aSR 1.99; 95% CI, 1.47-2.70), and drugs used in erectile dysfunction (aSR 1.85; 95% CI, 1.27-2.70). Other clinically relevant signals, ranked by number needed to harm (lowest to highest), included sulfonamides (NNTH 104; 95% CI, 98-111), electrolyte solutions (NNTH 216; 95% CI, 196-241), and osmotically acting laxatives (NNTH 710; 95% CI, 540-1056).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Potential PCs identified in this Medicare cohort reflected known and underrecognized adverse effects of DHP-CCBs. Further studies are needed to evaluate the clinical consequences of these PCs.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.15.26353346","type":"posted-content","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:10:14Z","timestamp":1779307814000},"source":"Crossref","is-referenced-by-count":0,"title":["Dihydropyridine Calcium Channel Blocker-induced Prescribing Cascades: Signal Detection using High-throughput Sequence Symmetry Analysis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7382-4358","authenticated-orcid":false,"given":"Priyanka J.","family":"Kulkarni","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, Gainesville, Florida, USA"},{"name":"Center for Drug Evaluation and Safety (CoDES), Gainesville, Florida, 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