A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model.

Abstract

The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017). The statin DDI exposed and unexposed groups were matched (2:1) through propensity score matching techniques. We applied a multistate transition model to compare the 1-year transition probabilities involving four distinct states (start, adverse drug events [ADEs], discontinuation of CYP3A4-inhibitor drugs, and discontinuation of statin therapy) between those exposed to statin DDIs vs. those unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. After concurrently starting stains and CYP3A, patients exposed to statin DDIs, vs. unexposed, were significantly less likely to discontinue statin therapy (71.4% [95% CI: 71.1, 71.6] vs. 73.3% [95% CI: 72.9, 73.6]) but more likely to experience an ADE (3.4% [95% CI: 3.3, 3.5] vs. 3.2% [95% CI: 3.1, 3.3]) and discontinue with CYP3A4-inhibitor therapy (21.0% [95% CI: 20.8, 21.3] vs. 19.5% [95% CI: 19.2, 19.8]). ADEs did not change these associations because those exposed to statin DDIs, vs. unexposed, were still less likely to discontinue statin therapy but more likely to discontinue CYP3A4-inhibitor therapy after experiencing an ADE. We did not observe any meaningful clinical differences in the probability of premature statin discontinuation between statin users exposed to statin DDIs and those unexposed.