title: Optimal strategies for monitoring lipid levels in patients at risk or with cardiovascular disease: a systematic review with statistical and cost-effectiveness modelling.
abstract: BACKGROUND
  Various lipid measurements in monitoring/screening programmes can be used, alone or in cardiovascular risk scores, to guide treatment for prevention of cardiovascular disease (CVD). Because some changes in lipids are due to variability rather than true change, the value of lipid-monitoring strategies needs evaluation.
  
  
  OBJECTIVE
  To determine clinical value and cost-effectiveness of different monitoring intervals and different lipid measures for primary and secondary prevention of CVD.
  
  
  METHODS
  We searched databases and clinical trials registers from 2007 (including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Clinical Trials Register, the Current Controlled Trials register, and the Cumulative Index to Nursing and Allied Health Literature) to update and extend previous systematic reviews. Patient-level data from the Clinical Practice Research Datalink and St Luke's Hospital, Japan, were used in statistical modelling. Utilities and health-care costs were drawn from the literature.
  
  
  METHODS
  In two meta-analyses, we used prospective studies to examine associations of lipids with CVD and mortality, and randomised controlled trials to estimate lipid-lowering effects of atorvastatin doses. Patient-level data were used to estimate progression and variability of lipid measurements over time, and hence to model lipid-monitoring strategies. Results are expressed as rates of true-/false-positive and true-/false-negative tests for high lipid or high CVD risk. We estimated incremental costs per quality-adjusted life-year.
  
  
  RESULTS
  A total of 115 publications reported strength of association between different lipid measures and CVD events in 138 data sets. The summary adjusted hazard ratio per standard deviation of total cholesterol (TC) to high-density lipoprotein (HDL) cholesterol ratio was 1.25 (95% confidence interval 1.15 to 1.35) for CVD in a primary prevention population but heterogeneity was high (I(2) = 98%); similar results were observed for non-HDL cholesterol, apolipoprotein B and other ratio measures. Associations were smaller for other single lipid measures. Across 10 trials, low-dose atorvastatin (10 and 20 mg) effects ranged from a TC reduction of 0.92 mmol/l to 2.07 mmol/l, and low-density lipoprotein reduction of between 0.88 mmol/l and 1.86 mmol/l. Effects of 40 mg and 80 mg were reported by one trial each. For primary prevention, over a 3-year period, we estimate annual monitoring would unnecessarily treat 9 per 1000 more men (28 vs. 19 per 1000) and 5 per 1000 more women (17 vs. 12 per 1000) than monitoring every 3 years. However, annual monitoring would also undertreat 9 per 1000 fewer men (7 vs. 16 per 1000) and 4 per 1000 fewer women (7 vs. 11 per 1000) than monitoring at 3-year intervals. For secondary prevention, over a 3-year period, annual monitoring would increase unnecessary treatment changes by 66 per 1000 men and 31 per 1000 women, and decrease undertreatment by 29 per 1000 men and 28 per 1000 men, compared with monitoring every 3 years. In cost-effectiveness, strategies with increased screening/monitoring dominate. Exploratory analyses found that any unknown harms of statins would need utility decrements as large as 0.08 (men) to 0.11 (women) per statin user to reverse this finding in primary prevention.
  
  
  CONCLUSIONS
  Heterogeneity in meta-analyses.
  
  
  CONCLUSIONS
  While acknowledging known and potential unknown harms of statins, we find that more frequent monitoring strategies are cost-effective compared with others. Regular lipid monitoring in those with and without CVD is likely to be beneficial to patients and to the health service. Future research should include trials of the benefits and harms of atorvastatin 40 and 80 mg, large-scale surveillance of statin safety, and investigation of the effect of monitoring on medication adherence.
  
  
  BACKGROUND
  This study is registered as PROSPERO CRD42013003727.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Rafael
authors.initials: R
authors.lastname: Perera
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: McFadden
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: McLellan
authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Tom
authors.initials: T
authors.lastname: Lung
authors.affiliation: Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Clarke
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pérez
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fanshawe
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dalton
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Farmer
authors.affiliation: Bond University, Gold Coast, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Glasziou
authors.affiliation: St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahashi
authors.affiliation: Patient and public involvement representativeUK.
authors.forename: John
authors.initials: J
authors.lastname: Stevens
authors.affiliation: Sydney School of Public Health, University of Sydney, Sydney, Australia.
authors.forename: Les
authors.initials: L
authors.lastname: Irwig
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hirst
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Stevens
authors.affiliation: St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Leslie
authors.affiliation: St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ohde
authors.affiliation: St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan.
authors.forename: Gautam
authors.initials: G
authors.lastname: Deshpande
authors.affiliation: St Luke's International University Center for Clinical Epidemiology, Tokyo, Japan.
authors.forename: Kevin
authors.initials: K
authors.lastname: Urayama
authors.affiliation: Oxford University Hospitals Trust, Oxford, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Shine
authors.affiliation: National Institute for Health Research School for Primary Care Research, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Stevens
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D008297:Male; D015233:Models, Statistical; D011322:Primary Prevention / Q000379:methods; D019057:Quality-Adjusted Life Years; D012307:Risk Factors; D013673:Technology Assessment, Biomedical
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids