title: Predicting the effects of blood pressure-lowering treatment on major cardiovascular events for individual patients with type 2 diabetes mellitus: results from Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation.
abstract: Blood pressure-lowering treatment reduces cardiovascular risk in patients with diabetes mellitus, but the effect varies between individuals. We sought to identify which patients benefit most from such treatment in a large clinical trial in type 2 diabetes mellitus. In Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) participants (n=11 140), we estimated the individual patient 5-year absolute risk of major adverse cardiovascular events with and without treatment by perindopril-indapamide (4/1.25 mg). The difference between treated and untreated risk is the estimated individual patient's absolute risk reduction (ARR). Predictions were based on a Cox proportional hazards model inclusive of demographic and clinical characteristics together with the observed relative treatment effect. The group-level effect of selectively treating patients with an estimated ARR above a range of decision thresholds was compared with treating everyone or those with a blood pressure >140/90 mm Hg using net benefit analysis. In ADVANCE, there was wide variation in treatment effects across individual patients. According to the algorithm, 43% of patients had a large predicted 5-year ARR of ≥1% (number-needed-to-treat [NNT5] ≤100) and 40% had an intermediate predicted ARR of 0.5% to 1% (NNT5=100-`200). The proportion of patients with a small ARR of ≤0.5% (NNT5≥200) was 17%. Provided that one is prepared to treat at most 200 patients for 5 years to prevent 1 adverse outcome, prediction-based treatment yielded the highest net benefit. In conclusion, a multivariable treatment algorithm can identify those individuals who benefit most from blood pressure-lowering therapy in terms of ARR of major adverse cardiovascular events and may be used to guide treatment decisions in individual patients with diabetes.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00145925.
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Joep
authors.initials: J
authors.lastname: van der Leeuw
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.). f.l.j.visseren@umcutrecht.nl.
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Sophia
authors.initials: S
authors.lastname: Zoungas
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Andre Pascal
authors.initials: AP
authors.lastname: Kengne
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Paul
authors.initials: P
authors.lastname: Glasziou
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Stephen
authors.initials: S
authors.lastname: MacMahon
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Neil
authors.initials: N
authors.lastname: Poulter
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.affiliation: From the Department of Vascular Medicine (J.v.d.L., F.L.J.V.), Julius Centre for Health Sciences and Primary Care (Y.v.d.G., D.E.G.), University Medical Centre Utrecht, Utrecht, The Netherlands; The George Institute for Global Health, University of Sydney, Sydney, Australia (M.W., S.Z., A.P.K., S.M., J.C.); NCRP for Cardiovascular and Metabolic Diseases, South African Medical Research Council and University of Cape Town, Cape Town, South Africa (A.P.K.); Centre for Research on Evidence Based Practice, Bond University, Robina, Queensland, Australia (P.G.); Centre Hospitalier de L'Université de Montréal, Montréal, Canada (P.H.); University of Oxford, Oxford, United Kingdom (S.M.); and Imperial College London, London, United Kingdom (N.P.).
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005907:Gliclazide / Q000008:administration & dosage*; D006801:Humans; D007004:Hypoglycemic Agents; D007190:Indapamide / Q000008:administration & dosage*; D008297:Male; D020913:Perindopril / Q000008:administration & dosage*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; C494243:indapamide, perindopril drug combination; D007190:Indapamide; D005907:Gliclazide; D020913:Perindopril
keywords: antihypertensive agents; diabetes mellitus; individualized medicine; medical decision making, computer-assisted