Factors associated with adherence to allocated treatment in the ASCEND trial: a mail-based randomised trial of aspirin and of omega-3 fatty acid supplementation in people with diabetes.
Madurasinghe VW., Mafham M., Buck G., Bowman L., Armitage J.
INTRODUCTION: ASCEND assessed the effects of randomisation to aspirin versus placebo and, separately omega-3 fatty acid (FA) supplementation versus placebo on vascular events in 15480 adults with diabetes using mail-based remote methods. This analysis investigates factors associated with adherence to the allocated treatments. METHODS: Adherence was estimated from the 6-monthly follow-up forms and the supply of study treatment packs. A binary adherence variable, full versus less than full adherence during the period at risk of a serious vascular event (SVE), was investigated using logistic regression. Potential predictors of adherence considered were sex, age at randomisation, Hospital Frailty Risk Score, ethnicity, Townsend index, smoking status, type of diabetes, predicted 5-year vascular risk, number of other medications reported at study entry and treatment allocation. RESULTS: Seven thousand, three hundred twelve (47.2%) participants were fully adherent to aspirin/placebo and 8937 (57.7%) were fully adherent to omega-3 FA/placebo while at risk of a SVE. Women were less likely to be fully adherent than men (aspirin randomisation: 2509 [43.3%] vs. 4803 [49.6%]; OR, 0.73; 95% CI: 0.68 to 0.80; P < 0.0001; omega-3 FA randomisation: 3035 [52.4%] vs. 5902 [61.0%]; OR, 0.67; 95% CI: 0.61 to 0.72; P < 0.0001) and adherence decreased with increasing frailty (trend p-value < 0.0001), smoking (p-value < 0.0001), vascular risk score (p-value < 0.0001) and deprivation (trend p-value = 0.0211, p = 0.0011). CONCLUSION: We show this large, mail-based trial has comparable adherence with less streamlined trials in similar populations. In ASCEND, women and those with higher levels of frailty, smoking and vascular risk score had poorer adherence to trial medication. Trialists should consider strategies to improve adherence in these participant groups.