title: Investigating the effectiveness of different aspirin dosing regimens and the timing of aspirin intake in primary and secondary prevention of cardiovascular disease: protocol for a systematic review.
abstract: BACKGROUND
  Once-daily low-dose aspirin is routinely used for the prevention of secondary events in cardiovascular disease (CVD). The routine use of aspirin in primary prevention of CVD is less clear due to a finer balance between benefits and harms. In addition, the variability in benefit achievable from the prescription of aspirin has led to a growing interest in considering whether there are more effective aspirin regimens than once-daily dosing or whether effectiveness is influenced by the time of day aspirin is taken (chronotherapy). The proposed systematic review will evaluate the evidence on the effects of different aspirin regimens used in terms of number of doses (e.g. split or alternate dosing) or dosing time of aspirin (e.g. morning versus evening) in primary and secondary prevention of CVD.
  
  
  METHODS
  Standard systematic review methodology will be employed for study identification, selection and data extraction. Electronic databases will be searched incorporating terms relating to population and the intervention. No date or language limitations will apply. Systematic reviews and controlled studies comparing different aspirin regimens-in terms of frequency or timing-for primary and/or secondary prevention of CVD will be included. No restrictions on outcome will apply. Quality assessment will be appropriate for each study design. The data will be tabulated and narratively synthesised. Meta-analysis may be undertaken where clinical and methodological homogeneity exists.
  
  
  CONCLUSIONS
  There are a number of published and ongoing primary studies that investigate the cardiovascular protective effect of different aspirin regimens. However, no systematic review to date has attempted to review the evidence pertaining to aspirin dosing regimens differing in frequency and/or in timing. The proposed systematic review will cover both the above questions and could potentially be beneficial for reconsidering the current practice of managing patients with aspirin in primary care.
  
  
  BACKGROUND
  PROSPERO CRD42014010596.
authors.affiliation: Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. d.bem@bham.ac.uk.
authors.forename: Danai
authors.initials: D
authors.lastname: Bem
authors.affiliation: Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. j.dretzke@bham.ac.uk.|NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, UK. j.dretzke@bham.ac.uk.
authors.forename: Janine
authors.initials: J
authors.lastname: Dretzke
authors.affiliation: Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. s.stevens@bham.ac.uk.
authors.forename: Simon
authors.initials: S
authors.lastname: Stevens
authors.affiliation: Montreal Heart Institute, Research Centre, 5000 rue Bélanger, Montréal, QC, H1T 1C8, Canada. marie.lordkipanidze@umontreal.ca.|Faculté de pharmacie, Université de Montreal, C.P. 6128, Succ. Centre-ville, Montreal, QC, H3C 3J7, Canada. marie.lordkipanidze@umontreal.ca.
authors.forename: Marie
authors.initials: M
authors.lastname: Lordkipanidzé
authors.affiliation: Primary Care Clinical Sciences, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. j.a.hodgkinson@bham.ac.uk.
authors.forename: James
authors.initials: J
authors.lastname: Hodgkinson
authors.affiliation: Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. s.bayliss@bham.ac.uk.
authors.forename: Sue
authors.initials: S
authors.lastname: Bayliss
authors.affiliation: Public Health, Epidemiology and Biostatistics, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. d.j.moore@bham.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Moore
authors.affiliation: Primary Care Clinical Sciences, School of Health and Population Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. d.a.fitzmaurice@bham.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Fitzmaurice
mesh_terms: D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D002985:Clinical Protocols; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011322:Primary Prevention / Q000379:methods*; D012107:Research Design; D055502:Secondary Prevention / Q000379:methods*; D000078202:Systematic Reviews as Topic
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin