Zhu, L, Hayen, A & Bell, KJL 2020, 'Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study.', Cardiovascular diabetology, vol. 19, no. 1.View/Download from: Publisher's site
BACKGROUND:The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid study found no evidence of a beneficial effect of statin-fibrate combined treatment, compared to statins alone, on cardiovascular outcomes and mortality in type 2 diabetes mellitus after 5 years of active treatment. However, a beneficial reduction in major CVD events was shown in a pre-specified sub-group of participants with dyslipidemia. The extended follow-up of this trial provides the opportunity to further investigate possible beneficial effects of fibrates in this group of patients. We aimed to evaluate possible "legacy effects" of fibrate add-on therapy on mortality and major cardiovascular outcomes in patients with dyslipidemia. METHODS:The ACCORD-lipid study was a randomized controlled trial of 5518 participants assigned to receive simvastatin plus fenofibrate vs simvastatin plus placebo. After randomized treatment allocation had finished at the end of the trial, all surviving participants were invited to attend an extended follow-up study (ACCORDION) to continue prospective collection of clinical outcomes. We undertook a secondary analysis of trial and post-trial data in patients who had dyslipidemia. The primary outcome was all-cause and cardiovascular mortality, and secondary outcomes were nonfatal myocardial infarction, stroke, congestive heart failure and major coronary heart disease. We used an intention-to-treat approach to analysis to make comparisons between the original randomized treatment groups. RESULTS:853 participants with dyslipidemia had survived at the end of the trial. Most participants continued to use statins, but few used fibrates in either group during the post-trial period. The incidence rates in the fenofibrate group were lower with respect to all-cause mortality, CVD mortality, nonfatal myocardial infarction, congestive heart failure and major coronary heart disease than those in the placebo group over a post-trial follow-up. Allocation to the combin...
Zhu, L, Bell, KJL & Hayen, A 2019, 'Estimated legacy effects from simulated post-trial data were less biased than from combined trial/post-trial data.', Journal of clinical epidemiology, vol. 114, pp. 30-37.View/Download from: Publisher's site
OBJECTIVES:"Legacy effects" describe the phenomena where treatment effects are apparent during the post-trial period that are not attributable to the direct effects observed within the trial. We investigate different approaches to analysis of trial and extended follow-up data for the evaluation of legacy effects. STUDY DESIGN AND SETTING:We conducted a simulation to compare three approaches, which differed in terms of the time period and selection of trial participants included in the analysis. RESULTS:The most common approach used for estimating legacy effects in the literature, which combines initial trial and post-trial follow-up data, gave the most biased estimates. Approaches using post-randomized controlled trial data had better performance in most scenarios. When the size of the legacy effect was set to differ according to whether or not drugs were taken after trial, the stratified approach using post-trial data but only from participants taking the drug after trial was less biased but often had lower power to detect a legacy effect. CONCLUSION:When estimating legacy effects, approaches to analysis that are restricted to post-trial follow-up data are preferred. If data are available on participant drug use after trial, then both stratified and unstratified approaches to analysis of the post-trial data should be investigated.