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). 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). AUTHORS' CONCLUSIONS: 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.

Plan de mejora de los indicadores de farmacia en un área sanitaria de atención primaria de Madrid: descripción y resultados / Plan for improving pharmacy indicators in a primary health area of Madrid. Description and results

ObjetivoEvaluar los resultados de un plan de mejora de los indicadores de farmacia de un Área Sanitaria de Atención Primaria (AP).DiseñoEstudio cuasiexperimental con grupo control. Se valoró la diferencia entre el periodo postintervención (ene–dic 2008) y preintervención (ene–dic 2007).Emplazamiento y participantesGrupo de intervención: médicos del Área 7 de AP de la Comunidad de Madrid (n=397). Grupo control: resto de médicos de AP de la Comunidad de Madrid (n=4.428).IntervenciónPlan de mejora multifocal cuyas principales acciones fueron: sesiones en los centros de salud con peores resultados, implicación de los responsables de Uso Racional del Medicamento, entrevistas con los médicos con indicadores más mejorables, reconocimiento de aquellos con buenos indicadores, elaboración notas breves sobre medicamentos.Mediciones principalesIndicadores de prescripción y de notificaciones relacionadas con la seguridad de los medicamentos.ResultadosEn relación a Madrid, las mejoras absolutas del Área 7 en los indicadores acumulados %EFG, %Estatinas elección, %ARAII y %Omeprazol fueron 0,29; 1,17; 0,61 y 0,37 puntos porcentuales, respectivamente. DHD Osteoporosis igualó la mejora de Madrid. En el Área 7, el incremento en las notificaciones de sospechas de RAM graves fue 180% y en el número de notificadores de RAM 233%, mejorando los datos de Madrid (48 y 21%). La notificación de errores de medicación presentó incrementos similares en ambos grupos (AP7 1.567% vs Madrid AP 1.633%).ConclusionesImplementar un plan de mejora multifocal con acciones factibles y concretas, puede ser una herramienta útil para la mejora de los indicadores de farmacia(AU)

ObjectiveTo evaluate the results of a plan for improving pharmacy indicators in a Primary Care (PC) Health Area.DesignQuasi-experimental study with a control group. The differences between the pre-intervention (Jan-Dec 2007) and post-intervention (Jan-Dec 2008) periods were evaluated.Setting and participantsIntervention group: Primary Care doctors from PC Area 7 of the Community of Madrid (n=397). Control group: the rest of PC doctors of the Community of Madrid (n=4428).MethodA multi-focus plan in which the main activities were: sessions in the health centres with the worst results, involvement of those responsible for the Rational Use of Drugs, interviews with the doctors with the most improvable indicators, recognition of those with good indicators, and preparing short notes on drugs.Main measurementsPrescription and notification indicators associated with the safety of drugs.ResultsIn relation to Madrid, the absolute improvements of Area 7 in the accumulated indicators, %Generic drugs, %Statins, %ARAII y %Omeprazole were 0.29; 1.17; 0.61 and 0.37 percentage points, respectively. DHD Osteoporosis equalled the improvement of Madrid. In Area 7, the increase in notifications of suspected serious ADRs was 180% and number of ADR notifications of ADRs was 233%, better than the Madrid data (48% and 21%). The notification of medication errors showed similar increases in both groups (PC Area 7 1567% vs. Madrid PC 1633%).ConclusionsImplementing a multi-focus improvement plan with feasible and specific actions can be a useful tool for improving pharmacy indicators(AU)

[Plan for improving pharmacy indicators in a primary health area of Madrid. Description and results]. / Plan de mejora de los indicadores de farmacia en un área sanitaria de atención primaria de Madrid: descripción y resultados.

OBJECTIVE: To evaluate the results of a plan for improving pharmacy indicators in a Primary Care (PC) Health Area. DESIGN: Quasi-experimental study with a control group. The differences between the pre-intervention (Jan-Dec 2007) and post-intervention (Jan-Dec 2008) periods were evaluated. SETTING AND PARTICIPANTS: Intervention group: Primary Care doctors from PC Area 7 of the Community of Madrid (n=397). CONTROL GROUP: the rest of PC doctors of the Community of Madrid (n=4428). METHOD: A multi-focus plan in which the main activities were: sessions in the health centres with the worst results, involvement of those responsible for the Rational Use of Drugs, interviews with the doctors with the most improvable indicators, recognition of those with good indicators, and preparing short notes on drugs. MAIN MEASUREMENTS: Prescription and notification indicators associated with the safety of drugs. RESULTS: In relation to Madrid, the absolute improvements of Area 7 in the accumulated indicators, %Generic drugs, %Statins, %ARAII y %Omeprazole were 0.29; 1.17; 0.61 and 0.37 percentage points, respectively. DHD Osteoporosis equalled the improvement of Madrid. In Area 7, the increase in notifications of suspected serious ADRs was 180% and number of ADR notifications of ADRs was 233%, better than the Madrid data (48% and 21%). The notification of medication errors showed similar increases in both groups (PC Area 7 1567% vs. Madrid PC 1633%). CONCLUSIONS: Implementing a multi-focus improvement plan with feasible and specific actions can be a useful tool for improving pharmacy indicators.