Ezetimibe boosts statin effect in ACS patients with dyslipidaemia, low EPA/AA ratio
The addition of ezetimibe improves statin treatment in acute coronary syndrome (ACS) patients with dyslipidaemia and low eicosapentaenoic acid-to-arachidonic acid (EPA/AA) ratio, resulting in a lowered risk of cardiovascular events compared to monotherapy, according to a study presented at the recently concluded 2019 Congress of the European Society of Cardiology (ESC 2019) held in Paris, France.
Researchers performed a sub-analysis of the HIJ-PROPER* study, where 1,734 ACS patients with dyslipidaemia were assigned to receive pitavastatin either alone or with ezetimibe. In the present study, participants were grouped into high (n=603; mean age, 68.7±9.8 years) and low (n=584; mean age, 62.6±12.6 years) EPA/AA groups based on a cutoff value of 0.34 µg/mL.
In the low EPA/AA group, the primary endpoint―a composite of all-cause death, nonfatal stroke and myocardial infarction, ischaemia-driven revascularization, and unstable angina pectoris―occurred in 36.6 percent and 27.2 percent of patients who received pitavastatin alone or with ezetimibe, respectively. [ESC 2019, abstract P824]
The resulting reduction in risk was statistically significant (hazard ratio [HR], 0.69, 95 percent CI, 0.52–0.93; p=0.02). This was driven primarily by the effect of add-on ezetimibe on ischaemia-driven revascularization, which occurred significantly less frequently in those who received the combination intervention (20.3 percent vs 30.4 percent; HR, 0.63, 0.45–0.87; p<0.01).
The other components of the primary composite outcome did not differ between treatment groups: all-cause death (HR, 0.65, 0.32–1.30; p=0.22), nonfatal myocardial infarction (HR, 0.43, 0.06–2.24; p=0.32) and stroke (HR, 2.1, 0.58–9.6; p=0.27), and unstable angina pectoris (HR, 1.35, 0.61–3.11; p=0.45).
Similarly, ezetimibe did not seem to yield any additional benefit for participants with high baseline EPA/AA, such that the primary composite outcome occurred with similar frequency between treatment groups (36.6 percent vs 33.0 percent; HR, 0.92, 0.70–1.20; p=0.52).
Disaggregation into the individual components did not change the initial finding.
Researchers then performed multivariable analysis in the low-EPA/AA group to search for independent predictors of the primary outcome. The use of ezetimibe was identified as a significant protective factor (HR, 0.70, 0.52–0.94; p=0.02), as were high-density lipoprotein cholesterol (HR, 0.88, 0.78–1.01; p=0.05) and docosahexaenoic acid (HR, 0.95, 0.91–0.99; p=0.04).
Glomerular filtration rate (HR, 0.92, 0.85–1.01; p=0.09) and non-ST elevation myocardial infarction (HR, 0.59, 0.29–1.06; p=0.08) also emerged as putative protective factors, though only of borderline significance.
“Among ACS patients who had dyslipidaemia with baseline EPA/AA ratio <0.34, combination therapy with ezetimibe and statin decreased the risk of cardiovascular events compared with statin monotherapy,” researchers concluded.
*Heart Institute of Japan-Proper level of lipid lowering with Pitavastatin and Ezetimibe in acute coronary syndrome