{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Navar AM"],"funding":["NHLBI NIH HHS"],"pagination":["e005041"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6541480"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["<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."],"journal":["Circulation. Cardiovascular quality and outcomes"],"pubmed_title":["Medication Discontinuation in the IMPROVE-IT Trial."],"pmcid":["PMC6541480"],"funding_grant_id":["K01 HL133416"],"pubmed_authors":["White JA","Giugliano RP","Califf RM","Newby LK","Navar AM","Blazing MA","Roe MT","Braunwald E","Tershakovec AM","Cannon CP","Lokhnygina Y"],"additional_accession":[]},"is_claimable":false,"name":"Medication Discontinuation in the IMPROVE-IT Trial.","description":"<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.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jan","modification":"2024-02-14T22:53:31.91Z","creation":"2020-05-22T01:34:43Z"},"accession":"S-EPMC6541480","cross_references":{"pubmed":["30630361"],"doi":["10.1161/circoutcomes.118.005041","10.1161/CIRCOUTCOMES.118.005041"]}}