EVALUATION OF MEDICATION PERSISTENCE IN THE IMPROVE-IT TRIAL

620 JACC April 5, 2016 Volume 67, Issue 13

Acute Coronary Syndromes EVALUATION OF MEDICATION PERSISTENCE IN THE IMPROVE-IT TRIAL Poster Contributions Poster Area, South Hall A1 Sunday, April 03, 2016, 3:45 p.m.-4:30 p.m. Session Title: Acute Coronary Syndromes: Implementing the Known and the Novel to Improve Outcomes Abstract Category: 15. Acute Coronary Syndromes: Therapy Presentation Number: 1215-024 Authors: Ann Marie Navar Boggan, Jennifer White, Yuliya Lokhnygina, L. Kristin Newby, Michael Blazing, Duke University, Durham, NC, USA Background: Cholesterol-lowering medications reduce the risk of recurrent cardiovascular disease, though medication discontinuation limits effectiveness. We evaluated medication persistence in the IMPROVE-IT trial: a long-term, placebo-controlled, randomized trial of simvastatin vs simvastatin/ezetimibe in patients after hospitalization with acute coronary syndrome.

Methods: Discontinuation reasons were evaluated by time on therapy: early (<30 days); intermediate (30 days-1 year) and late (to trial end, up to 8.8 years). Differences by treatment and geographic region were evaluated using Kaplan-Meier (KM) analysis.

Results: Overall, 46.7% of subjects discontinued medication. Discontinuation was highest in the first year (KM rate 20%), and declined with time (≤5% per year after year 3). Site-initiated reasons and subject desire to stop accounted for >50% of discontinuations (Table). Discontinuation was similar in the simvastatin arm compared with the simvastatin/ezetimibe arm (49.8% vs 52.0% at 7 years), was highest in the US (57.4% at 7 years), and lowest in South America (37.9%, p<0.001). Conclusions: Though discontinuation rates were highest in the first year of treatment, due to long-term follow-up, most discontinuations occurred after 1 year. Geographic differences were significant, but adding ezetimibe to statin therapy did not increase discontinuation risk. Medication persistence should be considered when planning and evaluating results of long-term clinical trials. Table: Reasons for Medication Discontinuation by Duration on Therapy Site-initiated discontinuationa Subject initiatedb Drug-related adverse eventc Not-drug-related serious adverse event Medical indication Known side effectsd Not-drug-related adverse event Other/unknown Drug-related serious adverse event

All SubjectsN=17,706

<30 DaysN=1048 295 (28.1%) 243 (23.2%) 229 (21.9%)

30 Days to 1 YearN=2466 720 (29.2%) 589 (23.9%) 361 (14.6%)

446 (5.4%)

34 (3.2%)

111 (4.5%)

301 (6.3%)

959 (11.6%) 756 (9.1%) 264 (3.2%) 215 (2.6%)

86 (8.2%) 70 (6.7%) 55 (5.2%) 17 (1.6%)

229 (9.3%) 306 (12.4%) 84 (3.4%) 35 (1.4%)

644 (13.5%) 380 (8.0%) 125 (2.6%) 163 (3.4%)

109 (1.3%)

19 (1.8%)

31 (1.3%)

59 (1.2%)

2383 (28.8%) 2063 (24.9%) 1078 (13.0%)

≥1 YearN=4759 1368 (28.7%) 1231 (25.9%) 488 (10.3%)

aSite designated failure to comply with protocol, LDL >100, loss to follow-up, withdrawn consent, moved with no accepting alternate site. bSubject requested discontinuation, poor compliance/did not want to take multiple. cInvestigator designated drug-related adverse event. Note: patient death not considered “discontinuation”. dMyalgias, elevated LFTs, elevated CK.