Background: Numerous studies demonstrate that, even with use of statins, many patients are unable to meet their LDL-C goals. This study examined modifications to statin and/or ezetimibe therapy among patients with hyperlipidemia and prior history of cardiovascular (CV) events in a US commercially insured population.Methods: Adults (age 18 years) initiating statins and/or ezetimibe between 1 January 2007 and 31 December 2008 were identified from HealthCore Integrated Research Database. The index date was the initiation date of statins and/or ezetimibe. All patients had 1 medical claims related to myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, or percutaneous coronary intervention within 12 months prior to the index date. Treatment modifications to statins and/or ezetimibe initiated on the index date (index therapy) included permanent discontinuation of any lipid lowering therapy (LLT), rechallenge, switching, subtraction, augmentation, and dose changes.Results: Among 17,902 patients, around 90% initiated with statin monotherapy, followed by statin and ezetimibe combination (3.0%: 18-64 years; 3.8%: 65 years). Ten percent or less initiated on high intensity statins. Most common treatment modifications were rechallenging index therapy (25.2%: 18-64 years, 27.0%: 65 years), switching (27.5%: 18-64 years, 24.6%: 65 years), and permanent discontinuation of any LLT (18.6%: 18-64 years, 21.0%: 65 years). Only 10% of patients in both groups underwent dose escalation.Conclusions: Real-world evidence indicates that few high-risk patients initiate therapy with high-intensity statins. More than 50% of patients underwent a rechallenge or switching. Despite high CVD risk profile, approximately 20% of patients permanently discontinued any LLT.Key limitations: Pharmacy claims do not provide information on whether patients who had a pharmacy fill actually took the medication as prescribed. It is unknown whether rechallenge was a simple delay in filling a prescription or an actual rechallenge of their index therapy. Reasons for treatment discontinuations or modifications were unavailable in claims data.