Screening for Statin-related Prescribing Cascades Using High-throughput Sequence Symmetry Analysis

Sunday, August 28, 2022

2:00 PM – 2:15 PM CEST

Location: C1M5

Publication Number: 249

Background: Statins are generally well-tolerated, but their ubiquitous use exposes millions to adverse events that may go undetected, prompting a new prescription to treat statin-associated adverse experiences — a phenomenon known as a prescribing cascade.

Objectives: To screen for potential statin-related prescribing cascades using high-throughput sequence symmetry analysis (SSA).

Methods: Using IBM Marketscan Commercial and Medicare Supplemental Claims from Jan 2005 to Dec 2019, we identified new statin users aged ≥20 years with continuous insurance enrollment ≥720 days before and ≥360 days after statin initiation. We screened statin initiators against all other drug classes (defined by anatomical therapeutic classification Level 4 codes) within 90 days of statin initiation using SSA. SSA generated sequence ratios relating the proportion of statin initiators who start the other drug class after, versus before, the statin, while adjusting for prescribing time trends (adjusted sequence ratios [aSRs]). We then calculated naturalistic numbers needed to harm (NNTH) ¬— the inverse of the number of other drug class initiators after starting a statin minus the number initiating before statin use, divided by the number of statin initiators. Three independent reviewers classified each significant signal as a potential prescribing cascade or not.

Results: Overall, 2,290,011 statin initiators were included. We screened 526 classes, of which 160 had a positive signal (significant aSR). After review, 47 signals (29.4%) were classified as potential prescribing cascades. The top 3 classes considered potential prescribing cascades, as ranked by NNTH, along with their potential indication, were: 1) osmotically acting laxatives (A06AD; constipation; NNTH 44); 2) opioids in combination with non-opioid analgesics (N02AJ; pain/myalgia; NNTH 81); 3) first generation cephalosporins (J01DB; skin infection; NNTH 204). Additionally, we identified other clinically relevant potential cascades including antiinfectives (S03AA; eye/ear infections; NNTH 781); acetylcholinesterases (N06DA; cognitive impairment; NNTH 1250); and dantrolene (M03CA, rhabdomyolysis; NNTH=30,523)

Conclusions: High-throughput SSA screening is a novel approach to identifying CV-related prescribing cascades. Further research is needed to confirm these signals using more traditional pharmacoepidemiological approaches

Presenting Author(s)

Scott M. Vouri, PharmD, PharmD, PhD, PhD

Assistant Professor
University of Florida College of Pharmacy
Gainesville, Florida, United States

Slides

Co-Author(s)

Earl J. Morris, IV, PharmD, MPH

University of Florida - Department of Pharmaceutical Outcomes & Policy
Gainesville, Florida, United States
MW

Marta Walsh

University of Florida College of Pharmacy, United States
LH

Leonie Hochleitner

University of Florida College of Pharmacy, United States
MM

Matthew Muschett

University of Florida College of Pharmacy, United States
JA

Jessica Agalliu

University of Florida College of Pharmacy, United States
AD

Alyssa Dempsey

University of Florida College of Pharmacy, United States
SS

Stephan Schmidt, PhD

Associate Professor, Director Center for Pharmacometrics and Systems Pharmacology
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA
Orlando, FL, United States
CP

Carl Pepine

University of Florida College of Medicine, United States
SS

Steven Smith

Assistant professor
2. Department of Pharmacotherapy & Translational Research, University of Florida College of Pharmacy, Gainesville, Florida, United States, United States