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Medication Discontinuation in the IMPROVE-IT Trial.

Publication ,  Journal Article
Navar, AM; Roe, MT; White, JA; Cannon, CP; Lokhnygina, Y; Newby, LK; Giugliano, RP; Tershakovec, AM; Braunwald, E; Califf, RM; Blazing, MA
Published in: Circ Cardiovasc Qual Outcomes
January 2019

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.

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Published In

Circ Cardiovasc Qual Outcomes

DOI

EISSN

1941-7705

Publication Date

January 2019

Volume

12

Issue

1

Start / End Page

e005041

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • South America
  • Risk Factors
  • Practice Patterns, Physicians'
  • North America
  • New Zealand
  • Middle Aged
  • Male
  • Lipids
 

Citation

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Navar, A. M., Roe, M. T., White, J. A., Cannon, C. P., Lokhnygina, Y., Newby, L. K., … Blazing, M. A. (2019). Medication Discontinuation in the IMPROVE-IT Trial. Circ Cardiovasc Qual Outcomes, 12(1), e005041. https://doi.org/10.1161/CIRCOUTCOMES.118.005041
Navar, Ann Marie, Matthew T. Roe, Jennifer A. White, Christopher P. Cannon, Yuliya Lokhnygina, L Kristin Newby, Robert P. Giugliano, et al. “Medication Discontinuation in the IMPROVE-IT Trial.Circ Cardiovasc Qual Outcomes 12, no. 1 (January 2019): e005041. https://doi.org/10.1161/CIRCOUTCOMES.118.005041.
Navar AM, Roe MT, White JA, Cannon CP, Lokhnygina Y, Newby LK, et al. Medication Discontinuation in the IMPROVE-IT Trial. Circ Cardiovasc Qual Outcomes. 2019 Jan;12(1):e005041.
Navar, Ann Marie, et al. “Medication Discontinuation in the IMPROVE-IT Trial.Circ Cardiovasc Qual Outcomes, vol. 12, no. 1, Jan. 2019, p. e005041. Pubmed, doi:10.1161/CIRCOUTCOMES.118.005041.
Navar AM, Roe MT, White JA, Cannon CP, Lokhnygina Y, Newby LK, Giugliano RP, Tershakovec AM, Braunwald E, Califf RM, Blazing MA. Medication Discontinuation in the IMPROVE-IT Trial. Circ Cardiovasc Qual Outcomes. 2019 Jan;12(1):e005041.

Published In

Circ Cardiovasc Qual Outcomes

DOI

EISSN

1941-7705

Publication Date

January 2019

Volume

12

Issue

1

Start / End Page

e005041

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • South America
  • Risk Factors
  • Practice Patterns, Physicians'
  • North America
  • New Zealand
  • Middle Aged
  • Male
  • Lipids