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      High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

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          Abstract

          Background

          Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention.

          Methods

          We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment.

          Results

          Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; P<0.00001) and 39% relative reduction in MACE (OR: 0.61; 95% CI: 0.45–0.83; P = 0.002). The benefit of high-dose statin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious.

          Conclusions

          High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for patients with acute coronary syndrome.

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          Most cited references48

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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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            Pravastatin Treatment Increases Collagen Content and Decreases Lipid Content, Inflammation, Metalloproteinases, and Cell Death in Human Carotid Plaques: Implications for Plaque Stabilization

            Background —The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. Methods and Results —Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less lipid by oil red O staining (8.2±8.4% versus 23.9±21.1% of the plaque area, P <0.05), less oxidized LDL immunoreactivity (13.3±3.6% versus 22.0±6.5%, P <0.001), fewer macrophages (15.0±10.2% versus 25.3±12.5%, P <0.05), fewer T cells (11.2±9.3% versus 24.3±13.4%, P <0.05), less matrix metalloproteinase 2 (MMP-2) immunoreactivity (3.6±3.9% versus 8.4±5.3%, P <0.05), greater tissue inhibitor of metalloproteinase 1 (TIMP-1) immunoreactivity (9.0±6.2% versus 3.1±3.9%, P <0.05), and a higher collagen content by Sirius red staining (12.4±3.1% versus 7.5±3.5%, P <0.005). Cell death by TUNEL staining was reduced in the pravastatin group (17.7±7.8% versus 32.0±12.6%, P <0.05). Conclusions —Pravastatin decreased lipids, lipid oxidation, inflammation, MMP-2, and cell death and increased TIMP-1 and collagen content in human carotid plaques, confirming its plaque-stabilizing effect in humans.
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              Efficacy of atorvastatin reload in patients on chronic statin therapy undergoing percutaneous coronary intervention: results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial.

              This study was designed to investigate whether an acute atorvastatin reload before percutaneous coronary intervention (PCI) protects patients receiving chronic statin therapy from periprocedural myocardial damage. Previous ARMYDA (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) studies demonstrated that short-term pre-treatment with atorvastatin reduces myocardial infarction during PCI in statin-naïve patients with both stable angina and acute coronary syndromes. A total of 383 patients (age 66 +/- 10 years, 305 men) with stable angina (53%) or non-ST-segment elevation acute coronary syndromes (47%) and chronic statin therapy (55% atorvastatin) undergoing PCI were randomized to atorvastatin reload (80 mg 12 h before intervention, with a further 40-mg pre-procedural dose [n = 192]) or placebo (n = 191). All patients received long-term atorvastatin treatment thereafter (40 mg/day). The primary end point was 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, or unplanned revascularization). The primary end point occurred in 3.7% of patients treated with atorvastatin reload and in 9.4% in the placebo arm (p = 0.037); this difference was mostly driven by reduction in periprocedural myocardial infarction. There was lower incidence of post-procedural creatine kinase-myocardial band and troponin-I elevation greater than the upper limit of normal in the atorvastatin arm (13% vs. 24%, p = 0.017, and 37% vs. 49%, p = 0.021, respectively). Multivariable analysis identified atorvastatin reload as a predictor of decreased risk of 30-day incidence of major adverse cardiac events (odds ratio: 0.50, 95% confidence interval: 0.20 to 0.80; p = 0.039), mainly in patients with acute coronary syndromes (82% relative risk reduction; p = 0.027). The ARMYDA-RECAPTURE trial suggests that reloading with high-dose atorvastatin improves the clinical outcome of patients on chronic statin therapy undergoing PCI. These findings may support a strategy of routine reload with high-dose atorvastatin early before intervention even in the background of chronic therapy.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                4 December 2014
                : 9
                : 12
                : e113352
                Affiliations
                [1]Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-Related Cardiovascular Disease, Ministry of Education, Beijing 100029, China
                Istituto Clinico S. Ambrogio, Italy
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: Y. Zhou. Performed the experiments: LW PP OZ XX SY. Analyzed the data: LW PP Y. Zhao. Wrote the paper: LW.

                Article
                PONE-D-14-17261
                10.1371/journal.pone.0113352
                4256370
                25473831
                72dece23-547b-4139-9142-ff62851c5945
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 May 2014
                : 22 October 2014
                Page count
                Pages: 21
                Funding
                This work was supported by the National Natural Science Foundation of China NO. 81270285 and NO. 81100198, the National Construction Program of Key Clinical specialist facility Project and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support code: ZY201303 ( http://www.bjah.gov.cn/gzdt/kyjy/xzzq/201403/P020140304488636040596.pdf). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Cardiology
                Clinical Medicine
                Oral Medicine
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.

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