Physicians' Academy for Cardiovascular Education

Score identifies high-risk patients that benefit from ezetimibe at the long-term

Atherothrombotic Risk Stratification and Ezetimibe for Secondary Prevention

Literature - Bohula EA, Morrow DA, Giugliano RP, et al. - J Am Coll Cardiol 2017;69:911–21


There are adequate, validated and guideline recommended risk stratification tools assisting with the short-term prognostication and therapeutic decision making in acute coronary syndrome (ACS), but less is available to predict long-term response to treatment in patients with stable ischaemic heart disease [1,2].

The TIMI Risk Score for Secondary Prevention (TRS 2°P) was recently developed to predict recurrent cardiovascular (CV) events in a large population of stable patients with previous myocardial infarction (MI). It is a simple 9-point risk stratification tool that incorporates older age, diabetes mellitus, hypertension, smoking, peripheral artery disease, previous stroke, previous coronary artery bypass grafting, history of heart failure and renal dysfunction [3,4].

In the IMPROVE-IT study, the addition of ezetimibe to simvastatin significantly reduced recurrent CV events in stabilised post-ACS patients [5]. In this analysis of the IMPROVE-IT trial, the TRS 2°P was evaluated in regard to the effective identification of post-ACS patients at higher risk for recurrent CV events, who have the greatest potential to benefit from the addition of ezetimibe to statin therapy. For this, patients were categorized as low-risk (0-1 risk factor), intermediate risk (2 risk factors) or high-risk (≥ 3 risk factors).

Main results


The TIMI Risk Score for Secondary Prevention (TRS 2°P) identifies high-risk patients who derive the greatest benefit from the addition of ezetimibe to statin therapy for the long-term secondary prevention after ACS. These results contribute to the selection of stabilised post-ACS patients, who may need ezetimibe as an add-on therapy.

Editorial comment

In his editorial article [6], Schwartz notes that the original IMPROVE-IT findings showed a modest clinical benefit with ezetimibe, corresponding to 350 patient-years of treatment to prevent 1 primary endpoint event, without reducing mortality rates. The analysis of Bohula et al, better identifies those patients who may benefit from the add-on ezetimibe therapy, showing with the use of TRS 2°P that high-risk patients in the IMPROVE-IT study had a higher benefit, corresponding to 111 patient-years of treatment with ezetimibe to avoid 1 CV death, MI or ischemic stroke. However, he also notes that the background statin therapy with 40 mg of simvastatin daily, is not the optimal post-ACS treatment. He concludes: ‘Therefore, irrespective of the current findings from the IMPROVE-IT trial, it remains an open question whether ezetimibe, or any other lipid-modifying therapy, improves outcomes after ACS if added to a background of high-intensity statin treatment. In the near future, this question may be answered with more certainty. Large outcome trials will report whether treatment with monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9), expected to lower LDL-C to a much greater degree than ezetimibe, reduces cardiovascular events. One of these trials is studying this approach in patients with recent ACS who are receiving optimal, high-intensity statin treatment. Risk scores such as that presented by Bohula et al. may prove useful to determine which patients derive the greatest benefit from new lipid-modifying therapies.’


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