Abstract: This review includes eight RCTs (767 participants analysed in morning and evening arms). The trials used different lipid-lowering regimens with statins (lovastatin: two trials; simvastatin: three trials; fluvastatin: two trials; pravastatin: one trial). All trials compared the effects between morning and evening statin administration. Trial length ranged from four to 14 weeks. We found a high risk of bias in the domain of selective reporting in three trials and in the domain of incomplete outcome data in one trial of the eight trials included. None of the studies included were judged to be at low risk of bias. None of the included RCTs reported data on cardiovascular mortality, cardiovascular morbidity, incidence of cardiovascular events, or deaths from any cause. Pooled results showed no evidence of a difference in total cholesterol (MD 4.33, 95% CI -1.36 to 10.01), 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence), low-density lipoprotein cholesterol (LDL-C) levels (MD 4.85 mg/dL, 95% CI -0.87 to 10.57, 473 participants, five trials, mean follow-up 9 weeks, low-quality evidence), high-density lipoprotein cholesterol (HDL-C) (MD 0.54, 95% CI -1.08 to 2.17, 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence) or triglycerides (MD -8.91, 95% CI -22 to 4.17, 510 participants, five trials, mean follow-up 9 weeks, low-quality evidence) between morning and evening statin administration. With regard to safety outcomes, five trials (556 participants) reported adverse events. Pooled analysis found no differences in statins adverse events between morning and evening intake (OR 0.71, 95% CI 0.44 to 1.15, 556 participants, five trials, mean follow-up 9 weeks, low-quality evidence). Limited and low-quality evidence suggested that there were no differences between chronomodulated treatment with statins in people with hyperlipidaemia as compared to conventional treatment with statins, in terms of clinically relevant outcomes. Studies were short term and therefore did not report on our primary outcomes, cardiovascular clinical events or death. The review did not find differences in adverse events associated with statins between both regimens. Taking statins in the evening does not have an effect on the improvement of lipid levels with respect to morning administration. Further high-quality trials with longer-term follow-up are needed to confirm the results of this review.

Plain-language summary: We found eight randomised controlled trials that compared the effects between morning and evening statin administration in 767 people. Each trial evaluated different types and doses of statins. These trials were published between 1990 and 2013 and were conducted in the USA, Canada, Germany, Finland, Japan, South Korea and Thailand. This review includes evidence identified up to November 2015. No trials assessed CVD clinical events or deaths. Evaluation of the available evidence indicated that there were no differences between evening or morning administration of statins in terms of lipid levels (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides). Additionally, there was no difference in the rate of adverse events associated with statins between both regimens. The evidence in this review is of low quality because of study limitations and imprecision. Larger studies are required to confirm these results.