title: Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study.
abstract: In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events.
  
  
  
  Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was <2% for 13% of the patients. About 30% had an ARR of >4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]).
  
  
  
  ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that may complement informed decision making.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00327418 (CARDS) and NCT00000542 (ALLHAT).
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Lotte
authors.initials: L
authors.lastname: Kaasenbrood
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Neil R
authors.initials: NR
authors.lastname: Poulter
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Peter S
authors.initials: PS
authors.lastname: Sever
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Helen M
authors.initials: HM
authors.lastname: Colhoun
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Shona J
authors.initials: SJ
authors.lastname: Livingstone
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: S Matthijs
authors.initials: SM
authors.lastname: Boekholdt
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.).
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.affiliation: From the Department of Vascular Medicine (L.K., F.L.J.V.) and Julius Centre for Health Sciences and Primary Care (Y.v.d.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; ICCH, Imperial College London, London, United Kingdom (N.R.P., P.S.S.); Biomedical Research Institute, University of Dundee, Dundee, Scotland, United Kingdom (H.M.C., S.J.L.); Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (S.M.B.); and University of Texas Health Science Center, Houston (S.L.P., B.R.D.). f.l.j.visseren@umcutrecht.nl.
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069059:Atorvastatin / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D000066491:Clinical Decision-Making; D003661:Decision Support Techniques; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D009656:North America / Q000453:epidemiology; D011237:Predictive Value of Tests; D065840:Protective Factors; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012537:Scandinavian and Nordic Countries; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D015337:Multicenter Studies as Topic; D000068456:Clinical Studies as Topic
chemical_list: D000959:Antihypertensive Agents; D000069059:Atorvastatin; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids
keywords: cardiovascular diseases; decision making, shared; diabetes mellitus; precision medicine; statins, HMG-CoA; treatment outcome