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

Abstract Aims To describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs. Methods A retrospective new-user cohort study design was used to identify (N=160828) patients who concurrently initiated CYP3A4-inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104774) vs. other statins (unexposed, n = 56054) from the MarketScan Commercial claims database (2012 – 2017). These 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. unexposed. Statistically significant differences were assessed by comparing the 95% confidence intervals (CIs) of probabilities. Results 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]) directly after concurrently starting stains and CYP3A. Subsequent to experiencing an ADE, those exposed to statin DDIs were still less likely to discontinue statin therapy but were significantly more likely to discontinue CYP3A4-inhibitor therapy. Conclusion While statin DDI exposure was associated with higher likelihood of ADEs, this did not increase the risk of premature statin discontinuation among patients exposed to statin DDIs, versus unexposed.