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1.
The efficacy and safety of statin in combination with ezetimibe compared with double-dose statin in patients with high cardiovascular risk: A meta-analysis.
Zhu, Y, Hu, H, Yang, J, Yao, Q, Xu, H, Yu, Y, Liu, T, Lin, S
Bosnian journal of basic medical sciences. 2020;(2):169-182
Abstract
Currently, statins are the first-line therapies for dyslipidemia and atherosclerotic cardiovascular disease, however, their hypolipidemic effects have not been satisfactory. We performed a meta-analysis to compare lipid-lowering efficacy and safety of ezetimibe and statin combination therapy with double-dose statin monotherapy in patients with high cardiovascular risk. Fourteen studies involving 3105 participants were included in the final analysis; 1558 (50.18%) participants received ezetimibe and statin combination therapy and 1547 (49.82%) received double-dose statin monotherapy. Eight studies reported the percentages of changes in several lipid parameters from baseline to endpoint in both groups. Lipid parameters changed more significantly in patients coadministered with ezetimibe and statin (low-density lipoprotein cholesterol [LDL-C]: MD = -9.39, 95% CI -13.36 to -5.42; non-high-density lipoprotein cholesterol [non-HDL-C]: MD = -10.36, 95% CI -14.23 to -6.50; total cholesterol [TC]: MD = -8.11, 95% CI -10.95 to -5.26; and triglyceride [TG]: MD = -5.96, 95% CI -9.12 to -2.80), with moderate to high heterogeneity among the studies. Two out of fourteen studies investigated several different statins. Our subgroup analysis showed that, compared with double-dose atorvastatin monotherapy, ezetimibe and atorvastatin combination therapy significantly decreased LDL-C, non-HDL-C, TC, and TG levels by 14.16%, 14.01%, 11.06%, and 5.96%, respectively (p < 0.001). No significant difference was found in the incidence of laboratory-related adverse events (AEs) between statin combination therapy and monotherapy. Overall, ezetimibe and statin combination therapy significantly decreased LDL-C, non-HDL-C, and TC levels in patients with high cardiovascular risk, among which ezetimibe combined with atorvastatin had the best therapeutic effect. Compared with ezetimibe and statin combination therapy, double-dose statin monotherapy did not increase the risk of AEs.
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2.
Association between statin use and incidence or progression of osteoarthritis: meta-analysis of observational studies.
Wang, J, Dong, J, Yang, J, Wang, Y, Liu, J
Osteoarthritis and cartilage. 2020;(9):1170-1179
Abstract
OBJECTIVE The objective of the study was to determine whether statin use could reduce the risk of the incidence or progression of osteoarthritis (OA). METHODS The PubMed, Embase, and Cochrane databases were systematically searched for observational studies on the association between statin use and OA. ORs and 95% CIs were directly retrieved or calculated. The Newcastle-Ottawa quality assessment scale was used for study quality assessment. Subgroup analysis, sensitivity analysis, and publication bias were conducted using Stata software. RESULTS A total of 11 studies (679807 participants) were identified from the systematic literature search. No significant association between statin use and incidence (OR = 1.010; 95% CI: 0.968 to 1.055; P = 0.638) or progression (OR = 1.076; 95% CI: 0.824 to 1.405; P = 0.589) of OA was found in our meta-analysis. The meta-analysis according to the symptomatic or radiological OA also found no significant association between statin use and OA. The subgroup analysis showed that atorvastatin (OR = 0.953; 95% CI: 0.911 to 0.998; P = 0.041) and rosuvastatin (OR = 1.180; 95% CI: 1.122 to 1.241; P < 0.0001) had opposite effects on OA. The results of the analysis according to the joint site, interval, and statin dose were all not significant. CONCLUSIONS Statin use may not be associated with a lower risk of incidence and progression of OA, regardless of joint site. The opposite effects of atorvastatin and rosuvastatin were detected in OA.
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3.
Effect of Evolocumab on Coronary Plaque Composition.
Nicholls, SJ, Puri, R, Anderson, T, Ballantyne, CM, Cho, L, Kastelein, JJP, Koenig, W, Somaratne, R, Kassahun, H, Yang, J, et al
Journal of the American College of Cardiology. 2018;(17):2012-2021
Abstract
BACKGROUND Incremental low-density lipoprotein (LDL) cholesterol lowering with the proprotein convertase subtilisin kexin type 9 inhibitor evolocumab regresses coronary atherosclerosis in statin-treated patients. OBJECTIVES The purpose of this study was to evaluate the effect of adding evolocumab to statin therapy on coronary plaque composition. METHODS A total of 968 statin-treated coronary artery disease patients underwent serial coronary intravascular ultrasound imaging at baseline and following 76 weeks of treatment with placebo or evolocumab 420 mg monthly. Plaque composition changes were determined in 331 patients with evaluable radiofrequency analysis of the ultrasound backscatter signal. RESULTS Compared with statin monotherapy, evolocumab further reduced LDL cholesterol (33.5 mg/dl vs. 89.9 mg/dl; p < 0.0001) and induced regression of percent atheroma volume (-1.2% vs. +0.17%; p < 0.0001) and total atheroma volume (-3.6 mm3 vs. -0.8 mm3; p = 0.04). No difference was observed between the evolocumab and placebo groups in changes in calcium (1.0 ± 0.3 mm3 vs. 0.6 ± 0.3 mm3; p = 0.49), fibrous (-3.0 ± 0.6 mm3 vs. -2.4 ± 0.6 mm3; p = 0.49), fibrofatty (-5.0 ± 1.0 mm3 vs. -3.0 ± 1.0 mm3; p = 0.49), and necrotic (-0.6 ± 0.5 mm3 vs. -0.1 ± 0.5 mm3; p = 0.49) volumes. An inverse correlation was observed between changes in LDL cholesterol and plaque calcification (r = -0.15; p < 0.001). CONCLUSIONS The addition of evolocumab to a statin did not produce differential changes in plaque composition compared with statin monotherapy. This suggests that evaluation of plaque morphology using virtual histology imaging may provide no incremental information about the plaque effects of evolocumab beyond measurement of plaque burden. (GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound [GLAGOV]; NCT01813422).
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4.
Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial.
Nicholls, SJ, Puri, R, Anderson, T, Ballantyne, CM, Cho, L, Kastelein, JJ, Koenig, W, Somaratne, R, Kassahun, H, Yang, J, et al
JAMA. 2016;(22):2373-2384
Abstract
IMPORTANCE Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated. OBJECTIVE To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients. DESIGN, SETTING, AND PARTICIPANTS The GLAGOV multicenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa and enrolling 968 patients presenting for coronary angiography. INTERVENTIONS Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420 mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins. MAIN OUTCOMES AND MEASURES The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. RESULTS Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%] women; mean LDL-C level, 92.5 mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6 mg/dL; difference, -56.5 mg/dL [95% CI, -59.7 to -53.4]; P < .001). The primary efficacy parameter, PAV, increased 0.05% with placebo and decreased 0.95% with evolocumab (difference, -1.0% [95% CI, -1.8% to -0.64%]; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab (difference, -4.9 mm3 [95% CI, -7.3 to -2.5]; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3% vs 47.3%; difference, 17.0% [95% CI, 10.4% to 23.6%]; P < .001 for PAV and 61.5% vs 48.9%; difference, 12.5% [95% CI, 5.9% to 19.2%]; P < .001 for TAV). CONCLUSIONS AND RELEVANCE Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01813422.
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5.
Rosuvastatin reduces ischemia-reperfusion injury in patients with acute coronary syndrome treated with percutaneous coronary intervention.
Jiang, F, Yang, J, Zhang, L, Li, R, Zhuo, L, Sun, L, Zhao, Q
Clinical cardiology. 2014;(9):530-5
Abstract
BACKGROUND Statins reduce the incidence of cardiovascular events after percutaneous coronary intervention (PCI), but no clinical studies have investigated the role of statins in ischemia-reperfusion injury after PCI. HYPOTHESIS Rosuvastatin could reduce ischemia-reperfusion injury in patients with acute coronary syndrome treated with PCI. OBJECTIVES We investigated the effects of rosuvastatin on ischemia-reperfusion injury in patients with acute coronary syndrome after PCI and evaluated short-term prognosis. METHODS Patients scheduled for emergent PCI were given either rosuvastatin for ≥6 months (10 mg/d, every night; n = 55) or no statins (control group; n = 65). Serum superoxide dismutase activity, malondialdehyde, brain natriuretic peptide (BNP), and high-sensitivity C-reactive protein (hs-CRP) were determined before and after PCI, as well as left ventricular ejection fraction and left ventricular end-diastolic volume. Major adverse cardiac events were observed at follow-ups for 6 months. RESULTS Superoxide dismutase activity in the rosuvastatin-treated group was higher than that of the control group; serum levels of malondialdehyde were lower. BNP and hs-CRP levels in the rosuvastatin-treated group were lower than that of the control group. Four weeks after PCI, the left ventricular ejection fraction in the treatment group was higher than that of the control group, and the left ventricular end-diastolic volume was lower. At the 6-month follow-up, there was no difference in major adverse cardiac events between the 2 groups. CONCLUSIONS Rosuvastatin before PCI reduced ischemia-reperfusion injury in patients with acute coronary syndrome, which suggests the importance of application of rosuvastatin before PCI for early intervention.
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6.
Effects of combination of statin and calcium channel blocker in patients with cardiac syndrome X.
Zhang, X, Li, Q, Zhao, J, Li, X, Sun, X, Yang, H, Wu, Z, Yang, J
Coronary artery disease. 2014;(1):40-4
Abstract
OBJECTIVES Statins and calcium channel blockers have been proven beneficial toward improvement of endothelial function. The aim of this study was to compare the effect of combination therapy of statin and calcium channel blocker with solo treatment in patients with cardiac syndrome X. METHODS AND RESULTS Sixty-eight patients with cardiac syndrome X were divided randomly into three groups: fluvastatin (40 mg/day, n=23), diltiazem (90 mg/day, n=22), and combination of fluvastatin (40 mg/day) and diltiazem (90 mg/day, n=23). At the end of 90 days, the coronary flow reserve was improved in the three groups (fluvastatin-treated group: 23.2%; diltiazem-treated group: 12.4%; fluvastatin+diltiazem-treated group: 29.1%, all P<0.05). The time to 1 mm ST segment depression increased significantly in the fluvastatin-treated group (from 241±97 to 410±140 s, P<0.05), the diltiazem-treated group (from 258±91 to 392±124 s, P<0.05), and the fluvastatin+diltiazem-treated group (from 250±104 to 446±164 s, P<0.05). The improvement in coronary flow reserve and prolonged time to 1 mm ST segment depression in the combination treatment group were more remarkable than in those who received monotherapy. Combination therapy also induced a significant increase (35.6%, P<0.05) in nitric oxide and an apparent reduction (48.7%, P<0.05) in endothelin-1. CONCLUSION Combination treatment with fluvastatin and diltiazem is more effective on endothelial function and exercise tolerance than solo treatment in patients with cardiac syndrome X. The benefits of these drugs may be related to the elevation of nitric oxide and reduction of endothelin-1.
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7.
Changes in serum interleukin-6 and high-sensitivity C-reactive protein levels in patients with acute coronary syndrome and their responses to simvastatin.
Luo, Y, Jiang, D, Wen, D, Yang, J, Li, L
Heart and vessels. 2004;(6):257-62
Abstract
The role of inflammation in acute coronary syndrome (ACS) and the mechanism by which statin treats ACS is explored. Serum high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) levels were measured in 50 patients with ACS [including 30 cases with unstable angina (UA) and 20 patients with acute myocardial infarction (AMI)], 34 patients with stable angina (SA), and 30 controls. Patients in the ACS group were randomly assigned to a simvastatin group (including a simvastatin AMI subgroup, n = 11 and a simvastatin UA subgroup, n = 14) and a routine group (including a routine AMI subgroup, n = 9 and a routine UA subgroup, n = 16). The simvastatin group was given simvastatin 20mg/day and the routine group a placebo. After a 3-week follow-up, serum hs-CRP, IL-6 levels, and serum lipid concentrations were measured again. Both serum IL-6 and hs-CRP levels were significantly higher in the ACS group (including the UA and AMI subgroups) than in the SA and control groups (P < 0.001). After 3 weeks of treatment with simvastatin, the serum IL-6, hs-CRP, total cholesterol, and low-density lipoprotein cholesterol levels were decreased significantly in the simvastatin group (P < 0.001), but no significant changes were observed in the routine group. No relationship was observed between the rate of decrease of serum IL-6 or hs-CRP and serum lipids levels. The hs-CRP level showed a significant correlation with IL-6 by Spearman's rank correlation analysis (P < 0.01). Inflammation plays an important role in the initiation of ACS. Simvastatin possesses an anti-inflammatory effect, independent of its lipid-lowering action, which may play an important role in the early treatment of ACS.