Abstract
Background Little is known of the acute effects of ezetimibe in patients with acute coronary syndrome (ACS) undergoing PCI. We investigated whether ezetimibe improves inflammation and vascular endothelial function in patients with ACS undergoing PCI. Methods We randomized 171 patients with ACS undergoing PCI to receive ezetimibe 10 mg/day plus rosuvastatin 20 mg/day (combination group, n = 81) versus rosuvastatin 20 mg/day (rosuvastatin group, n = 90). Lipid profile, type II secretory phospholipase A2 (sPLA2-IIa), interleukin-1β (IL-1β), vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were measured at baseline and after 7 days. Three months after PCI, clinical outcomes were examined. Result The levels of sPLA2-IIa and IL-1β reduced significantly in both groups, but more when ezetimibe and rosuvastatin were coadministered (sPLA2-IIa: 6.16 ± 2.67 vs. 7.42 ± 3.53 ng/ml, p=0.01; IL-1β: 37.39 ± 26.25 vs. 48.98 ± 32.26 pg/ml, p=0.01). A significant rise of VCAM-1 and ICAM-1 was observed on day 7 after PCI in the both groups, but was less in the combination group (VCAM-1: 918.28 ± 235.31 vs. 988.54 ± 194.41 ng/ml, p=0.03; ICAM-1: 213.01 ± 100.15 vs. 246.88 ± 105.71 ng/ml, p=0.03). Patients in the combination versus rosuvastatin group appeared to suffer from less major adverse events. Periprocedural therapy of ezetimibe improves rosuvastatin effects on proinflammatory responses and endothelial function associated with ACS patients undergoing PCI. This trial is registered with https://clinicaltrials.gov/ct2/show/ChiCTR-IPR-17012219 (Chinese Clinical Trial Registry, http://www.chictr.org.cn on 02/08/2017).
Highlights
Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are well-established first-line agents for the primary and secondary prevention of atherosclerotic cardiovascular disease [1, 2], mainly due to their powerful effect on lowering low-density lipoprotein cholesterol (LDL-C) levels [3] and anti-inflammatory property [4, 5]
In another trial, combination therapy with ezetimibe plus statin versus statin alone improved clinical outcomes of acute coronary syndrome (ACS) patients, including cardiovascular death, myocardial infarction, stroke, unstable angina leading to hospitalization and coronary revascularization ≥30 days during a median 6-year follow-up [11]
We hypothesized that the benefits of combination therapy may be partly related to its effects on inflammation and endothelial function in addition to further cholesterollowering. is study was designed to evaluate whether periprocedural combination therapy of ezetimibe plus statin improves postprocedural levels of blood parameters of inflammation and vascular endothelial dysfunction (VCAM-1and intercellular cell adhesion molecule-1 (ICAM-1)) in ACS patients undergoing selective percutaneous coronary intervention (PCI)
Summary
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are well-established first-line agents for the primary and secondary prevention of atherosclerotic cardiovascular disease [1, 2], mainly due to their powerful effect on lowering low-density lipoprotein cholesterol (LDL-C) levels [3] and anti-inflammatory property [4, 5]. A recent study evaluated the effects of dual LDL-Clowering therapy with ezetimibe-statin in patients with acute coronary syndrome (ACS) on IVUS-derived coronary atherosclerosis and showed stronger coronary plaque regression during a 9–12-month of follow-up, compared with statin monotherapy [10]. In another trial (the IMPROVE-IT trial), combination therapy with ezetimibe plus statin versus statin alone improved clinical outcomes of ACS patients, including cardiovascular death, myocardial infarction, stroke, unstable angina leading to hospitalization and coronary revascularization ≥30 days during a median 6-year follow-up [11]. We hypothesized that the benefits of combination therapy may be partly related to its effects on inflammation and endothelial function in addition to further cholesterollowering. is study was designed to evaluate whether periprocedural combination therapy of ezetimibe plus statin improves postprocedural levels of blood parameters of inflammation (sPLA2-IIa and IL-1β) and vascular endothelial dysfunction (VCAM-1and ICAM-1) in ACS patients undergoing selective PCI
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