Anticholesteremic Agents ; therapeutic use ; Atherosclerosis ; drug therapy ; Ezetimibe ; therapeutic use ; Humans

BACKGROUND: Acute coronary syndromes mainly result from abrupt thrombotic occlusion caused by atherosclerotic vulnerable plaques (VPs) that suddenly rupture or erosion. Fibrous cap thickness (FCT) is a major determinant of the propensity of a VP to rupture and is recognized as a key factor. The intensive use of statins is known to have the ability to increase FCT; however, there is a risk of additional adverse effects. However, lower dose statin with ezetimibe is known to be tolerable by patients. The present study aimed to investigate the effect of intensive statin vs. low-dose stain + ezetimibe therapy on FCT, as evaluated using optical coherence tomography. METHOD: Patients who had VPs (minimum FCT <65 μm and lipid core >90°) and deferred from intervention in our single center from January 2014 to December 2018 were included in the trial. They were divided into the following two groups: intensive statin group (rosuvastatin 15-20 mg or atorvastatin 30-40 mg) and combination therapy group (rosuvastatin 5-10 mg or atorvastatin 10-20 mg + ezetimibe 10 mg). At the 12-month follow-up, we compared the change in the FCT (ΔFCT%) between the two groups and analyzed the association of ΔFCT% with risk factors. Fisher exact test was used for all categorical variables. Student's t test or Mann-Whitney U-test was used for analyzing the continuous data. The relationship between ΔFCT% and risk factors was analyzed using linear regression analysis. RESULT: Total 53 patients were finally enrolled, including 26 patients who were in the intensive statin group and 27 who were in the combination therapy group. At the 12-month follow-up, the serum levels of total cholesterol (TC), total triglyceride, low-density lipoprotein (LDL-C), hypersensitive C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels were reduced in both the groups. The ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group. FCT was increased in both the groups (combination treatment group vs. intensive statin group: 128.89 ± 7.64 vs. 110.19 ± 7.00 μm, t = -9.282, P < 0.001) at the 12-month follow-up. The increase in ΔFCT% was more in the combination therapy group (123.46% ± 14.05% vs. 91.14% ± 11.68%, t = -9.085, P < 0.001). Based on the multivariate linear regression analysis, only the serum Lp-PLA2 at the 12-month follow-up (B = -0.203, t = -2.701, P = 0.010), ΔTC% (B = -0.573, t = -2.048, P = 0.046), and Δhs-CRP% (B = -0.302, t = -2.963, P = 0.005) showed an independent association with ΔFCT%. CONCLUSIONS Low-dose statin combined with ezetimibe therapy maybe provide a profound and significant increase in FCT as compared to intensive statin monotherapy. The reductions in Lp-PLA2, ΔTC%, and Δhs-CRP% are independently associated with an increase in FCT.
Anticholesteremic Agents/therapeutic use* ; Drug Therapy, Combination ; Ezetimibe/therapeutic use* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Plaque, Atherosclerotic/drug therapy* ; Rosuvastatin Calcium/therapeutic use* ; Tomography, Optical Coherence ; Treatment Outcome

Objective: To compare the efficacy and safety profile of alirocumab (PCSK9 inhibitor) versus ezetimibe on top of maximally tolerated statin dose in high cardiovascular risk Chinese patients with hyperlipidemia. Methods: The ODYSSEY EAST study was a randomized, double-blinded, double dummy, active-control, parallel group, multi-centers clinical trial, the Chinese sub-population included 456 patients with hyperlipidemia and high cardiovascular risk on maximally tolerated statin dose. Patients were randomized (2∶1) to receive the subcutaneous injection of alirocumab (75 mg Q2W; with dose up titration to 150 mg Q2W at week 12 if low-density lipoprotein cholesterol (LDL-C) was ≥1.81 mmol/L at week 8) or the oral administration of ezetimibe (10 mg daily) for 24 weeks. The primary endpoint was percentage change in calculated LDL-C from baseline to week 24. Key secondary efficacy endpoints included percentage change from baseline to week 12 or 24 in LDL-C (week 12) and other lipid parameters, including apolipoprotein (Apo) B, non-high-density lipoprotein cholesterol (non-HDL-C), TC, lipoprotein(a) (Lp(a)), HDL-C, fasting triglycerides (TG), and Apo A1, and the proportion of patients reaching LDL-C<1.81 mmol/L at week 24. Safety profile of therapeutic drugs was also assessed during the treatment period. Results: The mean age of 456 Chinese patients was (59.5±10.9) years, 341(74.8%) patients were male, 303 patients (66.4%) in alirocumab group and 153 patients (33.5%) in ezetimibe group. Demographic characteristics, disease characteristics, and lipid parameters at baseline were similar between the two groups. LDL-C was reduced more from baseline to week 12 and 24 in alirocumab group versus ezetimibe group, the difference of their least-squares mean (standard error) percent change were(-35.2±2.2)% and (-36.9±2.5)% (both P<0.001). At 12 weeks, alirocumab had significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-40.3±2.8)%, (-27.7±1.8)%, (-19.6±1.5)% and (-27.7±1.9)%, respectively (all P<0.001). At 24 weeks, the percent of patients who reached LDL-C<1.81 mmol/L and LDL-C<1.42 mmol/L was significantly higher in alirocumab group (85.3% and 70.5%) than in ezetimibe group (42.2% and 17.0%, both P<0.001), and alirocumab use was also associated with significant reduction on Lp(a), Apo B, total cholesterol and non HDL-C, the difference of their least-squares mean (standard error) percent change were (-37.2±2.8)%, (-29.1±2.0)%, (-21.6±1.6)% and (-29.6±2.2)%, respectively (all P<0.001). The incidence of treatment related adverse events was similar between the two treatment groups (223/302 patients (73.8%) in alirocumab group and 109/153 patients (71.2%) in ezetimibe group). Respiratory infection, urinary infection, dizziness and local injection-site reactions were the most frequently reported adverse events. Conclusions: In high cardiovascular risk patients with hyperlipidemia from China on maximally tolerated statin dose, the reduction of LDL-C induced by alirocumab is more significant than that induced by ezetimibe. Both treatments were generally safe during the observation period of study.
Aged ; Antibodies, Monoclonal, Humanized ; Anticholesteremic Agents/therapeutic use* ; Cardiovascular Diseases/drug therapy* ; China ; Double-Blind Method ; Ezetimibe/therapeutic use* ; Humans ; Hypercholesterolemia ; Hyperlipidemias ; Male ; Middle Aged ; Proprotein Convertase 9 ; Risk Factors ; Treatment Outcome

INTRODUCTIONWe aimed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia.

METHODSA double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile, oxidised low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hsCRP) and soluble intercellular cell adhesion molecule (sICAM) in dyslipidaemic patients with or at high risk of coronary artery disease, and compare it with atorvastatin 10 mg monotherapy. 30 patients were randomised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks.

RESULTSOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference -14.4 ± 6.5, 95% confidence interval [CI] -1.0 to -27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference -19.9 ± 6.1, 95% CI -7.4 to -32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.

CONCLUSIONCombination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy.

Anti-Inflammatory Agents ; therapeutic use ; Anticholesteremic Agents ; administration & dosage ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Drug Therapy, Combination ; methods ; Dyslipidemias ; drug therapy ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; Humans ; Hypolipidemic Agents ; therapeutic use ; India ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipoproteins, LDL ; metabolism ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; Treatment Outcome