Comparative Efficacy and Safety of Statin Monotherapy and Statin plus Ezetimibe Combination in a Real-World Setting.

BACKGROUND: The objective of this study was to conduct a comparative evaluation of the effectiveness of ezetimibe in combination with statins or statin monotherapy in patients with hypercholesterolemia in a real-world setting. METHODS: It was a retrospective multicenter observational study conducted in Russia. We included patients who received statins or a combination of statins with ezetimibe for ≥3 months. The primary endpoint of this study was the frequency of achieving low-density lipoprotein cholesterol (LDL-C) goal levels at the time of enrollment in the study (%). RESULTS: The full analysis set consisted of 1000 patients: 250 subjects in the statin monotherapy group and 750 subjects in the combination group. The groups did not differ in clinical, demographic, or laboratory variables, except for a higher prevalence of hypertension and higher baseline lipid values in the statin monotherapy group. During treatment, the LDL-C concentration decreased by 1.10 ± 1.04 mmol/L (change of -27.5 ± 28.5% from baseline) in the statin monotherapy group and by 1.55 ± 1.17 mmol/L (change of -38.2 ± 25.6% from baseline) in the combination therapy group, p < 0.001. The target LDL-C level was achieved in 22.4% of the patients in the monotherapy group compared with 28.8% of the patients in the combination therapy group, p = 0.049. CONCLUSIONS: In real-world clinical practice, statin/ezetimibe combination therapy demonstrated a more frequent achievement of target LDL-C levels compared with statin monotherapy. The addition of ezetimibe to statin therapy increased the probability of achieving LDL-C level goals by 29%.

Verification of Underlying Genetic Cause in a Cohort of Russian Patients with Familial Hypercholesterolemia Using Targeted Next Generation Sequencing.

Russian patients with familial hypercholesterolemia (FH) were screened for pathogenic mutations using targeted next generation sequencing. Genetic testing was performed in 52 probands with definite or probable FH based on the Dutch lipid clinic network criteria (DLCN score ≥6). Blood samples were studied by massive parallel sequencing (Illumina HiSeq 1500 platform) using a custom capture library related to dyslipidemia and premature atherosclerosis. Mutations considered to be responsible for monogenic FH were identified in 48% of the probands: 24 with mutations in the LDLR gene and two with a mutation in the APOB gene. There were 22 pathogenic/likely pathogenic mutations in LDLR, eight of which have not been previously described in the literature. Four patients with a clinical picture of homozygous FH had two heterozygous LDLR mutations. Although mutation-negative patients had highly elevated total cholesterol and low-density lipoprotein cholesterol levels, only half of them had a family history of hypercholesterolemia. With respect to heterozygous FH, mutation-positive patients had higher maximum total cholesterol levels (p = 0.01), more severe carotid atherosclerotic lesions, and a higher percentage of premature peripheral artery disease (p = 0.03) than mutation-negative ones. However, the number of patients who suffered from myocardial infarction was similar between the two groups.

Subclinical arterial wall damage in patients at low to moderate cardiovascular risk.

AIM: The aim of this paper is to study the degree of subclinical arterial wall damage in subjects at low and moderate risk of cardiovascular death by the SCORE scale using instrumental research methods. METHODS: We enrolled 600 patients (mean age 49.0 +/- 7.1 years, 74% women) with a calculated SCORE 5%, who passed a carotid duplex ultrasonography with a measurement of the intima-media thickness (IMT) and carotid plaque (CP) severity. In the study a computer sphygmography was also performed on the subjects to determine ankle-brachial pulse wave velocity (abPWV) and an ankle-brachial index (ABI). RESULTS: We found 389 (64%) patients with subclinical signs of atherosclerosis. CPs were found in 359 patients (60%), thickened IMT in 28 patients (5%), increased abPWV in 227 patients (38%), and ABI of <0.9 in 29 patients (5%). In the patients with a thickened IMT only two had no CPs. In contrast, 92% of the patients with CPs had normal IMT. Increased abPWV was determined in 87% participants with CPs, and only in 30 subjects no CPs were found. All 29 patients with an ABI of less than 0.9 had CPs. The "presence of CP"was the most sensitive parameter in the patients included in the study, in terms of atherosclerosis determination (92%). The identification of individuals with CPs significantly increased in men over 45 years of age (in 68.4% of cases, P = 0.009), and in women over 50 (in 61.8% of cases, P = 0.001). CONCLUSION: Our data reinforces the importance of non-invasive imaging of atherosclerosis in subjects at low and moderate cardiovascular risk. The study demonstrated a high prevalence of subclinical atherosclerosis signs in patients at low to moderate risk by the SCORE scale and a high detection frequency of carotid plaques. This suggests that wider implementation of carotid ultrasound in primary care algorithms may improve risk stratification with timely initiation of preventive strategies.

The influence of rosuvastatin therapy and percutaneous coronary intervention on angiogenic growth factors in coronary artery disease patients.

OBJECTIVE: The aim of our investigation was to assess the influence of rosuvastatin therapy and myocardial revascularization on angiogenic growth factors in coronary artery disease patients. METHODS AND RESULTS: Two main groups were examined: group one consisted of patients with successful percutaneous coronary intervention and group two consisted of patients 3 months on rosuvastatin therapy.Vascular endothelial growth factor (VEGF), VEGF receptor Flt-1 (sVEGF-R1) and transforming growth factor beta-1 (TGF-beta1) levels were measured in healthy volunteers and CAD patients before and 6 days after myocardial revascularization.VEGF and basic fibroblast growth factor (bFGF) levels were measured before and 3 months after rosuvastatin therapy, as well as total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), C-reactive protein (CRP), interleukin 6 (IL-6) and endothelium-dependent vasodilation. VEGF levels did not differ, but beta-TGF levels were significantly lower in CAD patients in comparison with healthy subjects, P < 0.0001. Myocardial revascularization caused changes of VEGF levels from 192.4 +/- 166.1 pg/ml to 264.7 +/- 226.6 pg/ml (P = 0.0066). There were positive changes in lipid levels, lowering of CRP and IL-6 concentrations, improving of endothelial function and decreasing of VEGF levels from 382 +/- 249 pg/ml to 297 +/- 220 pg/ml (P = 0.006) 3 months after rosuvastatin treatment. CONCLUSIONS: There is an elevation of VEGF levels early after myocardial revascularization that may reflect a transient ischaemia and potentially may provoke atherosclerotic plaque neovascularization. Rosuvastatin leads to a decrease of VEGF levels that can be a reflection of the influence on endogenous angiogenesis. There was no correlation between inflammatory factors and VEGF that gives a suggestion about an absence of direct CRP and IL-6 impact on VEGF decreasing during statin treatment.