biostudies-literatureNavar AMNHLBI NIH HHSe005041https://www.ebi.ac.uk/biostudies/studies/S-EPMC6541480biostudies-literatureUnknown12(1)<h4>Background</h4>Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials.<h4>Methods and results</h4>We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8-85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%-51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2-8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P=0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates.<h4>Conclusions</h4>Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis.<h4>Clinical trial registration</h4>URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.Circulation. Cardiovascular quality and outcomesMedication Discontinuation in the IMPROVE-IT Trial.PMC6541480K01 HL133416White JAGiugliano RPCaliff RMNewby LKNavar AMBlazing MARoe MTBraunwald ETershakovec AMCannon CPLokhnygina YfalseMedication Discontinuation in the IMPROVE-IT Trial.<h4>Background</h4>Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials.<h4>Methods and results</h4>We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8-85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%-51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2-8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P=0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates.<h4>Conclusions</h4>Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis.<h4>Clinical trial registration</h4>URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.2019-01-01T00:00:00Z2019 Jan2024-02-14T22:53:31.91Z2020-05-22T01:34:43ZS-EPMC65414803063036110.1161/circoutcomes.118.00504110.1161/CIRCOUTCOMES.118.005041