Concomitant use of levothyroxine and interacting medications in U.S. ambulatory care visits.

BACKGROUND: Levothyroxine (LT4) is the third most commonly prescribed medication in the United States. It is a narrow therapeutic index medication, and thus can be impacted by drug-drug interactions, which are primarily available over-the-counter. The prevalence and associated factors with concomitant interacting drugs with LT4 is limited since over-the-counter products are not routinely captured in many drug databases. OBJECTIVE: This study aimed to characterize the concomitant use of LT4 with interacting drugs at ambulatory care visits in the United States. DESIGN: A cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) from 2006 to 2018 was completed. SETTING AND PARTICIPANTS: Ambulatory care visits in the United States involving adult patients with a LT4 prescription were included in the analysis. OUTCOME MEASURES: The primary outcome was initiation or continuation of a selected concomitant interacting drug which impacts LT4 absorption (e.g., proton pump inhibitor) in a patient visit in conjunction with LT4. RESULTS: The authors analyzed 372,942,000 visits (weighted from a sample of 14,880) with a reported LT4 prescription. Concomitant use of interacting drugs with LT4 occurred in 24.4% of visits in which 80% of interacting drugs were proton pump inhibitors. Ages 35-49 years (adjusted odds ratio [aOR], 1.59), 50-64 years (aOR, 2.27), and ≥65 years (aOR, 2.87) compared to 18-34 years, female (aOR 1.37) versus males, and visits in 2014 or later (aOR, 1.27) versus 2006-2009 were associated with increased odds of concomitant interacting drug use in multivariable analysis. CONCLUSION: At ambulatory care visits between 2006 and 2018, concomitant use of LT4 and interacting drugs impacted one-quarter of patient visits. Increased age, females, and visits later in the study period were associated with increased odds for concomitant interacting drugs. Additional work is needed to identify downstream consequences of concomitant use.

High-throughput screening for prescribing cascades among real world statin initiators.

PURPOSE: Statins 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. METHODS: We 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. RESULTS: We 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). CONCLUSIONS: Using 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.

Impact of the ABCD-GENE Score on Clopidogrel Clinical Effectiveness after PCI: A Multi-Site, Real-World Investigation.

The Age, Body mass index, Chronic kidney disease, Diabetes mellitus, and CYP2C19 GENEtic variants (ABCD-GENE) score was developed to identify patients at risk for diminished antiplatelet effects with clopidogrel after percutaneous coronary intervention (PCI). The objective of this study was to validate the ability of the ABCD-GENE score to predict the risk for atherothrombotic events in a diverse, real-world population of clopidogrel-treated patients who underwent PCI and received clinical CYP2C19 genotyping to guide antiplatelet therapy. A total of 2,341 adult patients who underwent PCI, were genotyped for CYP2C19, and received treatment with clopidogrel across four institutions were included (mean age 64 ± 12 years, 35% women, and 20% Black). The primary outcome was major atherothrombotic events, defined as the composite of all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina within 12 months following PCI. Major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, myocardial infarction, ischemic stroke, or stent thrombosis, was assessed as the secondary outcome. Outcomes were compared between patients with an ABCD-GENE score ≥ 10 vs. < 10. The risk of major atherothrombotic events was higher in patients with an ABCD-GENE score ≥ 10 (n = 505) vs. < 10 (n = 1,836; 24.6 vs. 14.7 events per 100 patient-years, adjusted hazard ratio (HR) 1.66, 95% confidence interval (CI), 1.23-2.25, P < 0.001). The risk for MACE was also higher among patients with a score ≥ 10 vs. < 10 (16.7 vs. 10.1 events per 100 patient-years, adjusted HR 1.59, 95% CI 1.11-2.30, P = 0.013). Our diverse, real-world data demonstrate diminished clopidogrel effectiveness in post-PCI patients with an ABCD-GENE score ≥ 10.