Medication Discontinuation in the IMPROVE-IT Trial

Ann Marie Navar, Matthew T. Roe, Jennifer A. White, Christopher P. Cannon, Yuliya Lokhnygina, L. Kristin Newby, Robert P. Giugliano, Andrew M. Tershakovec, Eugene Braunwald, Robert M. Califf, Michael A. Blazing

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e005041
JournalCirculation. Cardiovascular quality and outcomes
Volume12
Issue number1
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Keywords

  • acute coronary syndrome
  • cholesterol
  • ezetimibe
  • medication adherence
  • statin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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