Prediction of absolute risk reduction of cardiovascular events with perindopril for individual patients with stable coronary artery disease - results from EUROPA

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.