title: The impact of dosing frequency on medication adherence in chronic cardiovascular disease: systematic review and meta-analysis.
abstract: OBJECTIVE
  Non-adherence to drug treatment is a major health problem. In Europe, it has been estimated that 9% of cardiovascular events can be attributed to non-adherence. The complexity of dosing regimens is one of the factors identified as contributing to non-adherence. In this systematic review we aimed to assess the impact of dosing frequency on adherence to drug treatment in patients with chronic cardiovascular disease.
  
  
  METHODS
  MEDLINE and the Cochrane Library (November 2013) were searched for randomized controlled trials (RCTs) comparing different dosing regimens (once-daily administration vs. two or more daily administrations) and assessing adherence to therapy in patients with chronic cardiovascular disease. Only trials with at least five months of follow-up were included. The results of the studies were pooled through a random effects meta-analysis. Relative risk (RR) and 95% confidence interval (CI) were derived. Statistical heterogeneity was calculated using the I(2) test.
  
  
  RESULTS
  Four RCTs (a total of 2557 patients) were included. Dosing regimens with once-daily administration were associated with a significant 56% reduction in risk of non-adherence to drug therapy (RR: 0.44; 95% CI: 0.35-0.54, I(2)=25%).
  
  
  CONCLUSIONS
  Few clinical trials have assessed the long-term impact of dosing frequency on medication adherence in chronic cardiovascular disease. The best available evidence suggests that taking medication once daily decreases the risk of non-adherence to treatment by approximately 50%. The impact on clinical outcomes remains to be established.
authors: Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal; Unidade de Farmacologia Clínica, Instituto Medicina Molecular, Lisboa, Portugal. Electronic address: dgcaldeira@hotmail.com.
authors: Daniel
authors: D
authors: Caldeira
authors: Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal; Centro Colaborador Português da Rede Cochrane Iberoamericana, Portugal.
authors: António
authors: A
authors: Vaz-Carneiro
authors: Laboratório de Farmacologia Clínica e Terapêutica, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal; Unidade de Farmacologia Clínica, Instituto Medicina Molecular, Lisboa, Portugal; Centro de Estudos de Medicina Baseada na Evidência, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal; Centro Colaborador Português da Rede Cochrane Iberoamericana, Portugal.
authors: João
authors: J
authors: Costa
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy*; D002908:Chronic Disease; D004334:Drug Administration Schedule; D006801:Humans; D016903:Drug Monitoring
keywords: Adesão medicamentosa; Adesão terapêutica; Cardiovascular disease; Chronic disease; Compliance do doente; Doença crónica; Doenças cardiovasculares; Drug administration regimen; Medication adherence; Patient compliance; Posologia de administração diária; Treatment adherence