AbstractPurposeStatins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin‐related prescribing cascades has been performed to our knowledge.MethodsWe utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes (“marker” classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005–2019). Order of initiation and secular trend‐adjusted sequence ratios were calculated for each statin‐marker class dyad, among marker class initiators ±90 days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1 year as the inverse of the excess risk among exposed.ResultsWe identified 2 265 519 statin initiators (mean ± SD age, 56.4 ± 12.0 years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin‐marker class dyad signals, of which 35.6% (n = 57) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43–46), opioids + non‐opioid combination analgesics (81, 95% CI 74–91), and first‐generation cephalosporins (204, 95% CI 175–246).ConclusionsUsing high‐throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin‐related adverse events.