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      Effect and safety of combination lipid‐lowering therapies based on statin treatment versus statin monotherapies on patients with high risk of cardiovascular events

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          Abstract

          This study aimed to compare the effect and safety of statin monotherapies and combination therapies on lipid‐lowing therapies. We searched for published randomized controlled trial ( RCT) reports of statin monotherapies and combination therapies in patients with high risk of cardiovascular events, and extracted lipid levels to perform meta‐analysis. A total of 12 RCT reports were included in this study. According to the new guidelines (low‐density lipoprotein cholesterol [ LDL‐C] < 100 mg/dL, high‐density lipoprotein cholesterol [ HDL‐C] > 130 mg/dL), the percent of LDL‐C attaining goals in combination therapy is more than that of monotherapy (risk ratio [ RR] = 1.43, 95% confidence interval [ CI]: 1.13 to 1.82, =  0.003), and the percent of LDL‐C and HDL‐C attaining goals in combination therapy is greater than that of monotherapy ( RR = 1.43, 95% CI: 1.24 to 1.65, =  0.000). The changing level of blood lipid had significant statistical difference between the two groups. The degree of blood lipid lowered by combination therapy was larger than in monotherapy (standard mean difference [ SMD] = −0.45, 95% CI: −0.75 to −0.14, =  0.004; SMD = −0.72, 95% CI: 0.04 to 1.39, =  0.039; and SMD = −0.71, 95% CI: −1.12 to −0.3, =  0.001 in LDL‐C, HDL‐C, and triglyceride, respectively). The incidence of adverse events was not significantly different between the two groups ( RR = 1.15, 95% CI: 0.91 to 1.37, =  0.096; RR = 1.5, 95% CI: 0.55 to 4.1, =  0.427; RR = 0.63, 95% CI: 0.33 to 1.24, =  0.181 in incidence of total adverse events, drug‐related treatment, and myalgia, respectively). Combination therapy can bring better effect in reducing lipid. It does not increase the incidence of adverse events, so it can be used widely and safely.

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          Simvastatin with or without ezetimibe in familial hypercholesterolemia.

          Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown. We conducted a double-blind, randomized, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia. Patients underwent B-mode ultrasonography to assess the intima-media thickness of the walls of the carotid and femoral arteries. The primary outcome measure was the change in the mean carotid-artery intima-media thickness, which was defined as the average of the means of the far-wall intima-media thickness of the right and left common carotid arteries, carotid bulbs, and internal carotid arteries. The primary outcome, the mean (+/-SE) change in the carotid-artery intima-media thickness, was 0.0058+/-0.0037 mm in the simvastatin-only group and 0.0111+/-0.0038 mm in the simvastatin-plus-ezetimibe (combined-therapy) group (P=0.29). Secondary outcomes (consisting of other variables regarding the intima-media thickness of the carotid and femoral arteries) did not differ significantly between the two groups. At the end of the study, the mean (+/-SD) LDL cholesterol level was 192.7+/-60.3 mg per deciliter (4.98+/-1.56 mmol per liter) in the simvastatin group and 141.3+/-52.6 mg per deciliter (3.65+/-1.36 mmol per liter) in the combined-therapy group (a between-group difference of 16.5%, P<0.01). The differences between the two groups in reductions in levels of triglycerides and C-reactive protein were 6.6% and 25.7%, respectively, with greater reductions in the combined-therapy group (P<0.01 for both comparisons). Side-effect and safety profiles were similar in the two groups. In patients with familial hypercholesterolemia, combined therapy with ezetimibe and simvastatin did not result in a significant difference in changes in intima-media thickness, as compared with simvastatin alone, despite decreases in levels of LDL cholesterol and C-reactive protein. (ClinicalTrials.gov number, NCT00552097 [ClinicalTrials.gov].). Copyright 2008 Massachusetts Medical Society.
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            Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins.

            Niacin reduces coronary heart disease morbidity and mortality when taken either alone or in combination with statins; however, the incremental impact of adding niacin to background statin therapy is unknown. This was a double-blind randomized placebo-controlled study of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease and low levels of high-density lipoprotein cholesterol (HDL-C; <45 mg/dL). The primary end point was the change in common carotid intima-media thickness (CIMT) after 1 year. Baseline CIMT (0.884+/-0.234 mm), low-density lipoprotein cholesterol (89+/-20 mg/dL), and HDL-C (40+/-7 mg/dL) were comparable in the placebo and niacin groups. Adherence to niacin exceeded 90%, and 149 patients (89.2%) completed the study. HDL-C increased 21% (39 to 47 mg/dL) in the niacin group. After 12 months, mean CIMT increased significantly in the placebo group (0.044+/-0.100 mm; P<0.001) and was unchanged in the niacin group (0.014+/-0.104 mm; P=0.23). Although the overall difference in IMT progression between the niacin and placebo groups was not statistically significant (P=0.08), niacin significantly reduced the rate of IMT progression in subjects without insulin resistance (P=0.026). Clinical cardiovascular events occurred in 3 patients treated with niacin (3.8%) and 7 patients treated with placebo (9.6%; P=0.20). The addition of extended-release niacin to statin therapy slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.
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              Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention: The Multicenter Randomized Controlled PRECISE-IVUS Trial.

              Despite standard statin therapy, a majority of patients retain a high "residual risk" of cardiovascular events.
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                Author and article information

                Contributors
                chenshuyan@xinhuamed.com.cn
                Journal
                Aging Med (Milton)
                Aging Med (Milton)
                10.1002/(ISSN)2475-0360
                AGM2
                Aging Medicine
                John Wiley and Sons Inc. (Hoboken )
                2475-0360
                04 September 2018
                September 2018
                : 1
                : 2 ( doiID: 10.1002/agm2.v1.2 )
                : 176-184
                Affiliations
                [ 1 ] Department of Geriatrics Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China
                Author notes
                [*] [* ] Correspondence

                Shuyan Chen, Department of Geriatrics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

                Email: chenshuyan@ 123456xinhuamed.com.cn

                Author information
                http://orcid.org/0000-0002-9099-5827
                Article
                AGM212032
                10.1002/agm2.12032
                6880669
                0cae1766-4f9c-4240-93c2-2bd904269f94
                © 2018 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 11 June 2018
                : 24 July 2018
                : 25 July 2018
                Page count
                Figures: 7, Tables: 1, Pages: 9, Words: 3983
                Funding
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81471399
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                September 2018
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.1 mode:remove_FC converted:12.11.2019

                cardiovascular events,combination therapy,lipid‐lowering,statin monotherapies

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