Biomarkers Identify Patients Who May Benefit From Ezetimibe Therapy

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Investigators evaluated the risk for recurrent cardiovascular events and clinical benefit with ezetimibe.

In patients with prior acute coronary syndrome (ACS), biomarkers can identify varying levels of risk for recurrent cardiovascular (CV) events, according to study results published in the Journal of the American College of Cardiology.

The findings indicate that this strategy can identify patients who would most benefit from the addition of ezetimibe to statin therapy.

The researchers conducted a pre-specified nested analysis with the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). The study included patients stabilized after ACS (N=18,144). The investigators randomly assigned patients 1:1 to either ezetimibe 10 mg daily or placebo in addition to simvastatin 40 mg daily and then followed the patients for a median of 6 years.

In their analysis, the researchers measured high-sensitivity troponin T, N-terminal pro–B-type natriuretic peptide, growth-differentiation factor-15, and high-sensitivity C-reactive protein in 7195 patients stabilized 1 month post-randomization after ACS. They used a multi-marker approach according to biomarker values to assess the risk for recurrent CV events and clinical benefit with ezetimibe.

The results indicated that elevated levels of each biomarker were independently associated with increased risk for CV death, myocardial infarction, stroke, and heart failure (P <.001 for each trend).

In patients at higher risk for CV events according to these biomarkers, the addition of ezetimibe to statin therapy showed a pattern of greater absolute risk reduction in CV death, myocardial infarction, and stroke.

With ezetimibe, patients who were at high risk (≥3 biomarkers “positive”; n=1437) had an absolute risk difference of −7.3% (95% CI, −13.8% to −0.8%; P =.02), and patients who were at intermediate risk (1 to 2 biomarkers “positive”; n=3842) had an absolute risk difference of −4.4% (95% CI, −9.7% to 0.8%).

Patients at low risk (0 biomarkers positive; n=1916) did not have significant risk reduction with the addition of ezetimibe to statin therapy.

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The study had several limitations. Because it is a secondary analysis of a large randomized clinical trial, the findings may not apply to the general population. In addition, the researchers did not collect angiographic or imaging data regarding the severity of coronary artery disease. They also noted these findings may not apply to other approaches to low-density lipoprotein cholesterol reduction such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition.

“Future studies should examine the role of biomarkers to guide patient selection for treatment with other low-density lipoprotein cholesterol–lowering drugs, such as PCSK9 inhibitors,” the researchers wrote.

Disclosures: This clinical trial was supported by Merck Sharp & Dohme Corp. Please see the original reference for a full list of authors’ disclosures.


Qamar A, Giugliano RP, Bohula EA, et al. Biomarkers and clinical cardiovascular outcomes with ezetimibe in the IMPROVE-IT trial. J Am Coll Cardiol. 2019;74(8):1057-1068.