The primary endpoint of the study was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs.,, 2020;30. A flow diagram of the study’s screening process has been shown in Fig. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data. 2019;26:199–207. This data suggest the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in significantly increased regression of TAV. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, et al. Multiple diagnostic methods have been used to assess the composition of atherosclerotic plaque. Statins for the primary prevention of cardiovascular disease. Another alternative to statins is bile acid–binding resins, or sequestrants. Synergistic effect of ezetimibe addition on coronary atheroma regression in patients with prior statin therapy: subanalysis of PRECISE-IVUS trial. Article  The process of plaque regression by aggressive LDL-C and non-HDL-C lowering therapy with non-statin drugs can occur. showed that the addition of ezetimibe to statin therapy is effective in reducing total atheroma volume assessed by IVUS [22]. Nicholls SJ, Puri R, Anderson T, Ballantyne CM, Cho L, Kastelein JJP, et al. It is therefore reasonable to think that the effects of the ezetimibe-statin combination therapy can vary according to the patient sample (e.g. 2016;23:1524–8. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. In fact, the pathophysiological mechanisms involved in acute coronary syndrome are not exactly the same as in chronic coronary heart disease. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. 2017;376:1713–22. PubMed  We consider that the number of studies evaluated approached the suggested number, being also the total of the available evidence at present. Ako J, Hibi K, Tsujita K, Hiro T, Morino Y, Kozuma K, et al. When the LDL-C and non-HDL-C levels reached were lower, the observed effect on atherosclerosis regression was also greater. 2018;66:70–2. 2019;170:779–83. In studies that included patients with acute coronary syndrome, the IVUS measurement was performed in a different coronary segment than the culprit lesion. Whayne TF. The following are key points to remember about the 2017 Focused Update of the 2016 American College of Cardiology (ACC) Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for Low-Density Lipoprotein (LDL)-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease (ASCVD) Risk: Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Keywords: Atherosclerosis, Cardiovascular Diseases, Cholesterol, Cholesterol, LDL, Consensus, Decision Making, Diabetes Mellitus, Dyslipidemias, Genetic Diseases, Inborn, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Life Style, Lipids, Lipid Metabolism, Inborn Errors, Lipoproteins, Patient Compliance, Primary Prevention, Proprotein Convertases, Risk Assessment, Risk Factors, Risk Reduction Behavior, Secondary Prevention, Subtilisins. 3. Since then, additional evidence, in particular related proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors, has been published. 2013;2013(1):CD004816. Tsujita K, Sugiyama S, Sumida H, Shimomura H, Yamashita T, Yamanaga K, et al. CurrAtheroscler Rep. 2018;20(1):2. Hougaard M, Hansen HS, Thayssen P, Antonsen L, Junker A, Veien K, et al. Nakajima N, Miyauchi K, Yokoyama T, Ogita M, Miyazaki T, Tamura H, et al. Dr. Luis Gutniski 3200, 3600, Formosa, Argentina, You can also search for this author in Nonstatin therapies reduced the risk of heart problems by 25 percent for each 1 millimole per liter (mmol/L) decrease in LDL cholesterol levels. 2012;76:176–83. In combination, the … Nevertheless, this study did not include a meta-regression to assess the relationship between the decrease in lipid markers achieved with dual lipid-lowering therapy and plaque regression. A literature search was performed that identified clinical trials of non-statin drugs that are recommended by the current cholesterol guidelines based on the results of clinical trials that showed efficacy in the reduction of cardiovascular events, and published between January 1990 and January 2020 in English. Circ J. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. Thresholds for consideration of ASCVD risk reduction are percent reduction in LDL (current LDL compared to baseline LDL). The atorvastatin/ezetimibe combination showed a significant stronger reduction in atheroma volume, compared with atorvastatin alone, in patients with statin pretreatment. Atherosclerosis. Martin Lobo and Juan Patricio Nogueira contributed to data assembly and analysis. 2020;28(3):744–55. Beyond cholesterol metabolism: the pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Medicina (B Aires). J Am Coll Cardiol. Earn CME/MOC Credit: Lowering Lipid Levels: Reducing Risk and Improving Outcomes, ACC and Medscape Collaboration: Cardiovascular Risk Reduction Center of Excellence, Congenital Heart Disease and     Pediatric Cardiology, Invasive Cardiovascular Angiography    and Intervention, Pulmonary Hypertension and Venous     Thromboembolism. N Engl J Med. Lipids Health Dis 19, 111 (2020). PCSK9 in relation to coronary plaque inflammation: results of the ATHEROREMO-IVUS study. Biofactors. Cochrane Database Syst Rev. Article  A large body of evidence supports a central role for LDL-C lowering in the prevention of atherosclerotic cardiovascular disease [41]. Mirzaee S, Thein PM, Nogic J, Nerlekar N, Nasis A, Brown AJ. Intravascular ultrasound-derived measures of coronary atherosclerotic plaque burden and clinical outcome. 2017;15:374–9. The summary effect of non-statin lipid- lowering drugs on the TAV was estimated. The follow-up ranged between 6 and 19 months. The use of statins has been and continues today to be the cornerstone of risk management of cardiovascular disease. Circ J. Role of non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression Abstract. Tsujita K, Yamanaga K, Komura N, Sakamoto K, Sugiyama S, Sumida H, et al. The GLAGOV trial reported the effectiveness of the PCSK9 inhibitor (evolocumab) compared with statin alone, on plaque regression at the LDL-C level of 36 mg/dL, further confirming “the lower the better” theory [20]. 2008;371:117–25. Ann Intern Med., DOI: 2014;3:8–13. To compare mean effects between subgroups, a Z test was used. Therefore, it seems reasonable to achieve lipid goals according to cardiovascular risk and regardless of the lipid-lowering strategy used (statin monotherapy or dual treatment). Fourth, this study was not designed to assess the cost effectiveness of non-statin therapy. Virtual histology evaluation of atherosclerosis regression during atorvastatin and ezetimibe administration: HEAVEN study. The quality of the studies evaluated can be seen in Fig. Low-density lipoprotein cholesterol (LDL-C): how low? Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. To view a copy of this licence, visit The dual therapy would be successful if it reduces an adequate percentage in lipid levels and, consequently, attains regression in the volume of atherosclerotic plaque. Article  The use of IVUS in the present analysis to evaluate atheroma volume is a globally established method to evaluate the vascular effect of lipid-lowering therapy. Lancet. Council of Epidemiology and Cardiovascular Prevention, Argentine Society of Cardiology, Azcuenaga 980, C1115AAD, Buenos Aires, Argentina, Walter Masson, Martin Lobo, Daniel Siniawski, Graciela Molinero, Gerardo Masson & Melina Huerín, Argentine Society of Lipids, Ambrosio Olmos 820, X5000JGQ, Córdoba, Argentina, Walter Masson, Daniel Siniawski & Juan Patricio Nogueira, Av. PubMed Central  Three years later, the ACC published its first expert consensus decision pathway related to the role of non-statin therapies for LDL-cholesterol lowering. The non-statin cholesterol-lowering medications are also effective at lowering LDL but to a lesser extent. Proprotein convertase subtilisin kexin type 9. PubMed  BMJ. 2016;16:87. Circ J. Eur Heart J. The funnel plot of standard error by mean difference of endpoints did not suggest publication bias Figure 6. 1. Manage cookies/Do not sell my data we use in the preference centre. Article  Absolute LDL or non–high-density lipoprotein (HDL) levels may be considered for each of the four statin benefit groups. In the same way, Begg and Mazumdar’s test for rank correlation gave a P value of 0.8046, not indicating possible publication bias. Coronary plaque regression has a significant positive correlation with low density lipoprotein cholesterol (LDL-C) and non-high-density-lipoprotein cholesterol (non-HDL-C) reduction [1]. TAV: total ateroma volumen; IVUS: intravascular ultrasound. 2016;251:367–72. J AtherosclerThromb. All rights reserved. For example, one of the pioneering investigations, the REVERSAL study, showed regression of the statin-mediated coronary plaque when the decrease in LDL-C level exceeded 50% [30]. Only 3 studies evaluated in this meta-analysis determined as an inclusion criteria having a baseline level of LDL-C > 100 mg/dl. 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. However, a recent meta-analysis failed to demonstrate an effect of PCSK9 inhibitors on high sensitivity C-reactive protein concentrations. Consideration of non-statin therapies to provide adequate percent LDL lowering was based on evidence from two trials: 1) FOURIER, which included patients with clinical ASCVD with or without DM; and SPIRE-2, which included high-risk primary prevention patients and patients with familial hypercholesterolemia. 111 ( 2020 ), Hu B, Bayturan O, Lavoie a, Horak J Mulrow. 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