Affiliation:
1. Department of Pharmaceutical Outcomes & Policy University of Florida College of Pharmacy Gainesville Florida USA
2. Center for Drug Evaluation and Safety University of Florida Gainesville Florida USA
3. Department of Pharmaceutics, College of Pharmacy University of Florida Orlando Florida USA
4. Division of Cardiovascular Medicine, Department of Medicine, College of Medicine University of Florida Gainesville Florida USA
5. Center for Integrative Cardiovascular and Metabolic Disease University of Florida Gainesville Florida USA
Abstract
AbstractStudy ObjectiveClinicians may prescribe new medications (marker drug) to treat statin‐related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin‐related adverse events.DesignA secondary analysis based on our previous work, a high‐throughput sequence symmetry analysis screening for potential statin‐related prescribing cascades.Data SourceMarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019.PatientsAdults who initiated a statin between 2007 and 2018, and who were continuously enrolled in the same healthcare plan for at least 720 days before and 360 days after statin initiation.InterventionAmong the previously identified 57 potential prescribing cascades, 42 statin‐marker class dyad with a sample size of ≥ 500 were assessed in this study.MeasurementsWe measured patients’ baseline characteristics within −360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CI) of modifiable statin characteristics after adjusting for baseline characteristics.Main ResultsWe identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low‐intensity statins, those initiating moderate‐ or high‐intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP‐4) inhibitors (aOR 1.22; 95% CI, 1.11–1.35) and glucagon‐like peptide‐1 (GLP‐1) analogs (aOR 1.31; 95% CI, 1.16–1.47), and opioids (aOR 1.18; 95% CI, 1.13–1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03–1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89–0.94).ConclusionCompared with low‐intensity statins, high‐intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally.