title: Prediction of absolute risk reduction of cardiovascular events with perindopril for individual patients with stable coronary artery disease - results from EUROPA.
abstract: BACKGROUND
  Angiotensin-converting-enzyme inhibition reduces the risk of cardiovascular events at a group level. Presumably, the absolute effect of treatment varies between individuals. We sought to develop multivariable prediction scores to estimate individual treatment effect of perindopril in patients with stable coronary artery disease (sCAD).
  
  
  METHODS
  In EUROPA trial participants, we estimated the individual patient 5-year absolute risk reduction (ARR) of major adverse cardiovascular events(MACE) by perindopril. Predictions were based on a new Coxproportional-hazards model with clinical characteristics and an external risk score in combination with the observed relative risk reduction. Second, a genetic profile modifying the relative efficacy of perindopril was added. The individual patient ARR was defined as the difference in MACE risk with and without treatment. The group level impact of selectively treating patients with the largest predicted treatment effect was evaluated using net benefit analysis.
  
  
  RESULTS
  The risk score combining clinical and genetic characteristics estimated the 5-year absolute treatment effect to be absent or adverse in 27% of patients. On the other hand, the risk score estimated a small 5-year ARR of ≤2% (NNT5≥50) in 20% of patients, a modest ARR of 2-4% (NNT5 25-50) in 26%, and a large ARR of ≥4% (NNT5≤25) in 28%. The external risk score yielded similar predictions. Selective prediction-based treatment resulted in higher net benefit compared to treat everyone at any treatment threshold.
  
  
  CONCLUSIONS
  A prediction score combining clinical characteristics and genetic information can quantify the ARR of MACE by perindopril for individual patients with sCAD and may be used to guide treatment decisions.
  
  
  BACKGROUND
  ISRCTN37166280.
authors.affiliation: Department of Vascular Medicine, University Medical Centre Utrecht, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: van der Leeuw
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rohit M
authors.initials: RM
authors.lastname: Oemrawsingh
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Brugts
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Jaap W
authors.initials: JW
authors.lastname: Deckers
authors.affiliation: Lille Heart Institute, Lille, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bertrand
authors.affiliation: Royal Brompton and National Heart Hospital, London, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Fox
authors.affiliation: Department of Cardiology and LTTA Centre, University Hospital of Ferrara and Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation, Cotignola, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: Remme
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Simoons
authors.affiliation: Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
authors.affiliation: Department of Vascular Medicine, University Medical Centre Utrecht, The Netherlands. Electronic address: f.l.j.visseren@umcutrecht.nl.
authors.forename: Frank L J
authors.initials: FL
authors.lastname: Visseren
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000066491:Clinical Decision-Making / Q000379:methods*; D003324:Coronary Artery Disease / Q000188:drug therapy*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000008:administration & dosage*; D057285:Precision Medicine / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril
keywords: Coronary artery disease; Medical decision making; Perindopril; Personalized medicine