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      Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials

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          Abstract

          Purpose

          The study sought to summarize the evidence of pre-procedural atorvastatin therapy to improve the prognosis of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).

          Patients and methods

          We searched PubMed and Embase from inception to July 2018 for randomized controlled trials that compared loading dose atorvastatin pretreatment with no or low dose for the prevention of cardiovascular events. The primary end points were all-cause mortality and myocardial infarction (MI) at 30 days. The secondary end point was 30-day major adverse cardiovascular events (MACE), a composite of all-cause mortality, MI, and revascularization.

          Results

          Six trials with 4,991 individuals were included in our meta-analysis. High-dose atorvastatin preloading before PCI was associated with a 27% relative reduction in MI (OR: 0.73, 95% CI, 0.56–0.94, P=0.015). All-cause mortality was nonsignificantly reduced by early treatment with high-potency atorvastatin (OR: 0.94, 95% CI, 0.69–1.30, P=0.725). There was a 20% reduction in MACE in the group of patients treated with statin loading prior to PCI (OR: 0.80, 95% CI, 0.66–0.97, P=0.026). When stratified according to the diagnosis of ACS, the results of MACE were only significant for those ST-elevation myocardial infarction patients undergoing PCI (OR: 0.67, 95% CI, 0.48–0.94, P=0.022) and were not noted in the group of non-ST elevation ACS patients (OR: 0.65, 95% CI, 0.35–1.22, P=0.179).

          Conclusion

          High-dose atorvastatin pretreatment leads to a significant reduction in MI and MACE at 30 days in ACS patients undergoing PCI, especially in ST-segment elevation MI.

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          Most cited references 18

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          Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial.

          This study sought to investigate potential protective effects of atorvastatin in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Randomized studies have shown that pretreatment with atorvastatin may reduce periprocedural myocardial infarction in patients with stable angina during elective PCI; however, this therapy has not been tested in patients with ACS. A total of 171 patients with non-ST-segment elevation ACS were randomized to pretreatment with atorvastatin (80 mg 12 h before PCI, with a further 40-mg preprocedure dose [n = 86]) or placebo (n = 85). All patients were given a clopidogrel 600-mg loading dose. All patients received long-term atorvastatin treatment thereafter (40 mg/day). The main end point of the trial was a 30-day incidence of major adverse cardiac events (death, myocardial infarction, or unplanned revascularization). The primary end point occurred in 5% of patients in the atorvastatin arm and in 17% of those in the placebo arm (p = 0.01); this difference was mostly driven by reduction of myocardial infarction incidence (5% vs. 15%; p = 0.04). Postprocedural elevation of creatine kinase-MB and troponin-I was also significantly lower in the atorvastatin group (7% vs. 27%, p = 0.001 and 41% vs. 58%, p = 0.039, respectively). At multivariable analysis, pretreatment with atorvastatin conferred an 88% risk reduction of 30-day major adverse cardiac events (odds ratio 0.12, 95% confidence interval 0.05 to 0.50; p = 0.004). The ARMYDA-ACS trial indicates that even short-term pretreatment with atorvastatin may improve outcomes in patients with ACS undergoing early invasive strategy. These findings may support routine use of high-dose statins before intervention in patients with ACS.
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            Antiatherothrombotic properties of statins: implications for cardiovascular event reduction.

            Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy have demonstrated that baseline or treated low-density lipoprotein (LDL) cholesterol levels are only weakly associated with net coronary angiographic change or cardiovascular events. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that modify endothelial function, inflammatory responses, plaque stability, and thrombus formation. Experimental animal models suggest that statins may foster stability through a reduction in macrophages and cholesterol ester content and an increase in volume of collagen and smooth muscle cells. The thrombotic sequelae caused by plaque disruption is mitigated by statins through inhibition of platelet aggregation and maintenance of a favorable balance between prothrombotic and fibrinolytic mechanisms. These nonlipid properties of statins may help to explain the early and significant cardiovascular event reduction reported in several clinical trials of statin therapy.
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              Clinical benefit of statin pretreatment in patients undergoing percutaneous coronary intervention: a collaborative patient-level meta-analysis of 13 randomized studies.

              Previous studies suggested that statin pretreatment reduces cardiac events in patients undergoing percutaneous coronary intervention. However, most data were observational, and single randomized trials included limited numbers of patients. We performed a collaborative meta-analysis using individual patient data from 13 randomized studies in which 3341 patients received either high-dose statin (n=1692) or no statin/low-dose statin (n=1649) before percutaneous coronary intervention, with all patients receiving statin therapy after intervention. Occurrence of periprocedural myocardial infarction, defined as postintervention creatine kinase-MB increase ≥3 times the upper limit of normal, and 30-day major adverse cardiac events (death, myocardial infarction, target-vessel revascularization) was evaluated. Incidence of periprocedural myocardial infarction was 7.0% in the high-dose statin versus 11.9% in the control group, which corresponds to a 44% risk reduction in the active-treatment arm (odds ratio by fixed-effects model 0.56, 95% confidence interval, 0.44 to 0.71, P<0.00001). The rate of major adverse cardiac events at 30 days was significantly lower in the high-dose statin group (7.4% versus 12.6%, a 44% risk reduction; P<0.00001), and 1-month major adverse cardiac events, excluding periprocedural events, were also reduced (0.6% versus 1.4%; P=0.05). The benefit of high-dose statins was realized irrespective of clinical presentation (P for interaction=0.43) and was maintained across various subgroups but appeared greater in the subgroup with elevated baseline C-reactive protein levels (n=734; 68% risk reduction for periprocedural myocardial infarction versus 31% in those 1861 patients with normal CRP; P for quantitative interaction=0.025). High-dose statin pretreatment leads to a significant reduction in periprocedural myocardial infarction and 30-day adverse events in patients undergoing percutaneous coronary intervention. This strategy should be considered in all patients with planned percutaneous coronary intervention.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2019
                16 April 2019
                : 13
                : 1233-1240
                Affiliations
                [1 ]Department of Cardiology, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, Guangdong 519000, People’s Republic of China
                [2 ]Department of Cardiovascular Medicine, Second Hospital of Shanxi University, Taiyuan, Shanxi 030001, People’s Republic of China
                [3 ]Department of Neurology, Fenyang Hospital of Shanxi Province, Fenyang, Shanxi 032200, People’s Republic of China
                [4 ]Department of Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630, People’s Republic of China, liangpingluo@ 123456126.com
                [5 ]Center of Intervention Radiology, Zhuhai Precision Medicine Center, Zhuhai People’s Hospital, Zhuhai, Guangdong 519000, People’s Republic of China, mamingfeng106@ 123456sina.com
                Author notes
                Correspondence: Ligong Lu, Center of Intervention Radiology, Zhuhai Precision Medicine Center, Zhuhai People’s Hospital, 79 Kangning Road, Zhuhai, Guangdong 519000, People’s Republic of China, Tel +861 380 251 1398, Email mamingfeng106@ 123456sina.com
                Liangping Luo, Department of Medical Imaging Center, The First Affiliated Hospital of Jinan University, 613 Huangpu West Road, Guangzhou, Guangdong 510630, People’s Republic of China, Tel +861 339 269 2103, Email liangpingluo@ 123456126.com
                Article
                dddt-13-1233
                10.2147/DDDT.S196588
                6585398
                © 2019 Ma et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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