To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme.Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism.Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score.The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362,809 patients and 792,665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90-1.66). There were 1449 renal dysfunction events among 272,099 patients and 574,584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58-1.44). There were 1434 hepatic dysfunction events among 367,612 patients and 815,945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45-1.31).Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy.
Background: In 2016, metformin’s prescribing label was revised to permit it to be started with estimated glomerular filtration rate (eGFR) 45-60 ml/min and continued with eGFR 30-44 ml/min. We examined whether subsequent metformin prescribing in these groups increased. Methods: We conducted an interrupted time series study using data from the New York City Clinical Data Research Network. We identified episodes from 2014-2017 in which adult patients with HbA1c ≥6.5% received outpatient antidiabetic prescriptions ≤7 days after an eGFR measurement. Trends in the proportion of episodes that included metformin were examined using linear regression in 4 eGFR subgroups: ≥60 (reference), 45-59, 30-44, and <30 ml/min. Sensitivity analysis examined episodes with no antidiabetic prescription in the prior 180 days. Results: We identified 10,608 prescribing episodes among 6,505 patients. Lower eGFR was associated with less metformin prescribing. In the eGFR 30-44 ml/min group, there were significant increases in metformin prescribing after the label change (p<0.001). In sensitivity analysis, an increasing trend in metformin prescriptions in the 45-59 ml/min eGFR group started before the label change (p=0.04) and leveled off. Conclusion: Metformin prescribing for patients with eGFR 30-60 ml/min was increasing prior to the label change. Rates of metformin use at eGFR 30-45 ml/min remain relatively low. Disclosure J. Min: None. X. Wu: None. J. Orloff: None. A.I. Mushlin: None. J. Flory: None. Funding Patient-Centered Outcomes Research Institute (CER-9230)
To compare rates of use and adherence for newer versus older second-line diabetes drug classes in commercially insured, Medicare Advantage and dual-eligible (covered by both Medicare and Medicaid) patients.
