Joep van der Leeuw1, Rohit M Oemrawsingh2, Yolanda van der Graaf3, Jasper J Brugts2, Jaap W Deckers2, Michel Bertrand4, Kim Fox5, Roberto Ferrari6, Willem J Remme7, Maarten L Simoons2, Eric Boersma2, Frank L J Visseren8. 1. Department of Vascular Medicine, University Medical Centre Utrecht, The Netherlands. 2. Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands. 3. Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands. 4. Lille Heart Institute, Lille, France. 5. Royal Brompton and National Heart Hospital, London, UK. 6. Department of Cardiology and LTTA Centre, University Hospital of Ferrara and Maria Cecilia Hospital, GVM Care & Research, E.S. Health Science Foundation, Cotignola, Italy. 7. Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands. 8. Department of Vascular Medicine, University Medical Centre Utrecht, The Netherlands. Electronic address: f.l.j.visseren@umcutrecht.nl.
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. CONCLUSION: 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. TRIAL REGISTRATION NUMBER: ISRCTN37166280.
RCT Entities:
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. CONCLUSION: 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. TRIAL REGISTRATION NUMBER: ISRCTN37166280.
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