Medication Discontinuation in the IMPROVE-IT Trial.

Autor:	Navar AM; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).; Duke Forge, Duke University, Durham, NC (A.M.N., R.M.C.)., Roe MT; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)., White JA; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)., Cannon CP; TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (C.P.C., R.P.G., E.B.)., Lokhnygina Y; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)., Newby LK; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.)., Giugliano RP; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).; TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (C.P.C., R.P.G., E.B.)., Tershakovec AM; Merck & Co, Inc, Rahway, NJ (A.M.T.)., Braunwald E; TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (C.P.C., R.P.G., E.B.)., Califf RM; Duke Forge, Duke University, Durham, NC (A.M.N., R.M.C.).; Department of Medicine, Stanford University, CA (R.M.C.).; Verily Life Sciences, South San Francisco, CA (R.M.C.)., Blazing MA; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
Jazyk:	angličtina
Zdroj:	Circulation. Cardiovascular quality and outcomes [Circ Cardiovasc Qual Outcomes] 2019 Jan; Vol. 12 (1), pp. e005041.
DOI:	10.1161/CIRCOUTCOMES.118.005041
Abstrakt:	Background: 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. Methods and Results: 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. Conclusions: 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. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.
Databáze:	MEDLINE
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