Endothelial function in high-risk patients with ezetimibe therapy

Merve Günes-Altan (Erlangen)1, A. Bosch (Erlangen)2, K. Striepe (Erlangen)2, M. Schiffer (Erlangen)2, S. Achenbach (Erlangen)1, R. E. Schmieder (Erlangen)2, D. Kannenkeril (Erlangen)2

1Universitätsklinikum Erlangen Medizinische Klinik 2 Erlangen, Deutschland; 2Universitätsklinikum Erlangen Medizinische Klinik 4 Erlangen, Deutschland


Background: Impaired endothelial function predicts cardiovascular (CV) events, especially in patients with established CV disease. The IMPROVE-IT study demonstrated that ezetimibe added to a statin therapy lowers the incidence of CV events in high-risk patients. The aim of this post hoc analysis was to compare the endothelial function between high-risk patients on optimized statin therapy with and without additional ezetimibe treatment.

Methods: A total of 91 patients with CV disease (diagnosis of coronary artery disease, non-hemorrhagic stroke, transient ischemic attack or symptomatic peripheral artery disease) and statin treatment (Atorvastatin or Rosuvastatin) were included. All patients underwent examination of endothelial function by a semi-automatic high-resolution ultrasound system (UNEX EF 18G; Unex Co., Nagoya, Japan). Endothelial function parameters such as flow-mediated vasodilation (FMD; vasodilator responsiveness), low flow-mediated vasoconstriction (L-FMC; vasoconstrictor responsiveness) and vasoactive range (VAR; total vasomotor responsiveness) were compared between patients with (E+) and without ezetimibe therapy (E-) (NCT03626831).

Results: Patients with ezetimibe treatment (n=21) were younger than patients without ezetimibe (n=70) (67 ± 7.4 versus. 61 ± 7.2 years; p=0.002), with mean low density lipoprotein cholesterol (LDL-C) of 91.2 ± 13.3 and 102 ± 18.1 mg/dl (p=0.013) and office systolic blood pressure (BP) of 123.9 ± 11.4 and 130.2 ± 14.5 mmHg (p=0.042), respectively. High sensitive c-reactive protein (hsCRP) was lower in E+ than in E- (0.53 ± 0.41 versus 1.1 ± 0.91 mg/L; p=0.002). We found a significantly higher FMD (6.1 ± 2.0 versus 3.7 ± 3.2 %; p=0.004) and lower brachial intima-media thickness (bIMT) (0.28 ± 0.1 versus 0.32±0.0 mm; p=0.011) in E+ compared to E-. L-FMC and VAR were not significantly different between the groups. When confounders (age, gender and systolic office BP) were entered in a covariance analysis, between-group differences of FMD (p=0.024) and hsCRP (p=0.049) remained significant.

In the overall cohort, we found an association between FMD and total cholesterol (r=-0.255, p=0.020) and a trend for LDL cholesterol (r=-0.208, p=0.059).

Conclusion: Our data indicate that endothelial function is better in high-risk patients with preexisting CV disease treated with ezetimibe along with statin. The results contribute to the mechanistic explanation of lower composite CV endpoint rates achieved by ezetimibe in the IMPROVE-IT study.

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