Chronotherapy versus conventional statins therapy for the treatment of hyperlipidaemia

Background Elevated levels of total cholesterol and low‐density lipoprotein play an important role in the development of atheromas and, therefore, in cardiovascular diseases. Cholesterol biosynthesis follows a circadian rhythm and is principally produced at night (between 12:00 am and 6:00 am). The adjustment of hypolipaemic therapy to biologic rhythms is known as chronotherapy. Chronotherapy is based on the idea that medication can have different effects depending on the hour at which it is taken. Statins are one of the most widely used drugs for the prevention of cardiovascular events. In usual clinical practice, statins are administered once per day without specifying the time when they should be taken. It is unknown whether the timing of statin administration is important for clinical outcomes. Objectives To critically evaluate and analyse the evidence available from randomised controlled trials regarding the effects of chronotherapy on the effectiveness and safety of treating hyperlipidaemia with statins. Search methods We searched the CENTRAL, MEDLINE, Embase, LILACS, ProQuest Health & Medical Complete, OpenSIGLE, Web of Science Conference Proceedings, and various other resources including clinical trials registers up to November 2015. We also searched the reference lists of relevant reviews for eligible studies. Selection criteria We included randomised controlled trials (RCTs), enrolling people with primary or secondary hyperlipidaemia. To be included, trials must have compared any chronotherapeutic lipid‐lowering regimen with statins and any other statin lipid‐lowering regimen not based on chronotherapy. We considered any type and dosage of statin as eligible, as long as the control and experimental arms differed only in the timing of the administration of the same statin. Quasi‐randomised studies were excluded. Data collection and analysis We used the standard methodological procedures expected by Cochrane. We extracted the key data from studies in relation to participants, interventions, and outcomes for safety and efficacy. We calculated odds ratios (OR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Using the GRADE approach, we assessed the quality of the evidence and we used the GRADEpro Guideline Development Tool to import data from Review Manager to create 'Summary of findings' tables. Main results This review includes eight RCTs (767 participants analysed in morning and evening arms).