An analysis of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT, ClinicalTrails.gov Identifier: NCT00202878) found that the highest rate of discontinuation of simvastatin plus placebo or ezetimibe plus simvastatin occurred in the first year. Factors associated with lipid-lowering therapy discontinuation include smoking, previous revascularization, hypertension, unstable angina, female sex, non-white race, and US residence. Findings from this analysis were reported in Circulation: Cardiovascular Quality and Outcomes.
The researchers included a total of 17,706 patients in the IMPROVE-IT who had been hospitalized for acute coronary syndrome in the analysis. Patients were randomly assigned to 40 mg of simvastatin plus either ezetimibe placebo (placebo plus simvastatin) or 10 mg ezetimibe (ezetimibe plus simvastatin).
The primary outcome measure was premature discontinuation, defined as permanent discontinuation of the study drug not due to study completion or death. Reasons for treatment discontinuation were assessed from the time of randomization through the end of the median 71.9-month (interquartile range, 51.8-85.8) study period. Rates of discontinuation were assessed at 30 days, 1 year, and through year 7.
Almost half of the patients (46.7%) discontinued the study drug by study end, with a Kaplan-Meier (KM) discontinuation rate of 50.9% (95% CI, 50.1%-51.7%). Although rates of discontinuation were highest early in the trial, discontinuation decreased over time.
The terminal KM rate per 100 person-years from years 1 through 7 was 8.4 (95% CI, 8.2-8.6). Rates of discontinuation were higher in patients randomly assigned to placebo plus simvastatin compared with patients who received ezetimibe plus simvastatin (52.0% vs 49.8%, respectively; P =.049).
In addition, discontinuation of statins was highest in the United States (7-year KM rate, 57.4%). Factors associated with and potentially predictive of discontinuation included smoking, previous revascularization, hypertension, unstable angina, female sex, non-white race, and US location.
A limitation of the analysis included the reliance on mostly study coordinator reports to assess reasons for discontinuation.
According to the investigators, the populations with the highest discontinuation rates “should be targeted for interventions to improve medication persistence at follow-up.”
Navar AM, Roe MT, White JA, et al. Medication discontinuation in the IMPROVE-IT trial. Circ Cardiovasc Qual Outcomes. 2019;12(1):e005041.