Early intensive statin treatment for six months improves long-term clinical outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a follow-up study. The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study Intensive Statin Therapy in NSTE-ACS Patients Undergoing PCI: Clinical and Biochemical Effects. Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial) Brief psychological intervention in phase I of cardiac rehabilitation after acute coronary syndrome. Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696] 12-month follow-up results of high dose rosuvastatin loading before percutaneous coronary intervention in patients with acute coronary syndrome. Early Statin Treatment in Patients With Acute Coronary Syndrome: Demonstration of the Beneficial Effect on Atherosclerotic Lesions by Serial Volumetric Intravascular Ultrasound Analysis During Half a Year After Coronary Event: The ESTABLISH Study Early high-dose rosuvastatin for contrast-induced nephropathy prevention in acute coronary syndrome: Results from the PRATO-ACS Study (Protective Effect of Rosuvastatin and Antiplatelet Therapy On contrast-induced acute kidney injury and myocardial damage in patients with Acute Coronary Syndrome). The expanded Global Registry of Acute Coronary Events: baseline characteristics, management practices, and hospital outcomes of patients with acute coronary syndromes. The early glycoprotein IIb/IIIa inhibition in non-ST-segment elevation acute coronary syndrome (EARLY ACS) trial: a randomized placebo-controlled trial evaluating the clinical benefits of early front-loaded eptifibatide in the treatment of patients with non-ST-segment elevation acute coronary syndro Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin  Underuse of evidence-based treatment modalities in diabetic patients with non-ST elevation acute coronary syndrome. A prospective nation wide study on acute coronary syndrome (FINACS). Effect of statin dose on incidence of atrial fibrillation: data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials. Endogenous tissue plasminogen activator and risk of recurrent cardiac events after an acute coronary syndrome in the MIRACL study.
BACKGROUND The ESTABLISH trial found using volumetric intravascular ultrasound that atorvastatin therapy started early and continued for 6 months significantly reduced plaque volume in patients with acute coronary syndrome ( ACS ) . However , the benefits of early statin administration on long-term outcomes remain unclear . We therefore examined whether the early initiation of statin in patients with ACS improves long-term prognosis . METHODS AND RESULTS The Extended-ESTABLISH trial included 180 patients with ACS who underwent emergency percutaneous coronary intervention ( PCI ) . These patients were r and omized here to groups given either early intensive lipid-lowering therapy ( n=90 ; atorvastatin 20 mg/day ) or st and ard care ( control , n=90 ) within 48 h of events . Baseline characteristics between the two groups did not significantly differ at the time of ACS onset . Six months after PCI , all patients were treated with statins to achieve an LDL-C value of < 100 mg/dL. We compared the first occurrence of major adverse cardiac and cerebrovascular events ( MACCE ) . Prognostic data were fully documented during the entire follow-up period ( mean , 1538+/-707 days ) . Cumulative event-free survival was significantly higher in the atorvastatin , than in the control group ( p=0.041 ; log-rank test ) . Furthermore , by adjusting for vali date d prognosticators , early statin administration was identified as a good predictor of MACCE ( HR 0.46 , 95%CI 0.23 - 0.86 ; p=0.015 ) . CONCLUSIONS In-hospital initiation of statin therapy immediately after ACS conferred long-term benefits and 6 months of intensive lipid-lowering therapy improved long-term clinical outcomes after PCI in patients with ACS We investigated the effects of atorvastatin on inflammation and cardiac events during the inpatient period and initial 6-month follow-up in acute coronary syndrome ( ACS ) patients with low low-density lipoprotein ( LDL ) cholesterol level . One hundred and twelve consecutive ACS patients with LDL cholesterol less than 100 mg/dl were included in the study ( mean 78.2 ± 12.3 mg/dl ) . While 70 r and omly selected patients received a dose of 40 mg atorvastatin within the first 24 h on top of their st and ard treatment as the atorvastatin group , the remaining 42 patients considered as the control group were given the st and ard treatment only , i.e. , without any lipid-lowering drug therapy .  Lipid profile , high-sensitivity C-reactive protein ( hsCRP ) , and plasma amyloid A ( SAA ) levels were measured in all patients within the first 24 h of chest pain , on the 5th day , and in the 6th month . During the inpatient period and subsequent 6-month follow-up , all episodes of angina , reinfa rct ion , revascularization , heart failure , rehospitalization , cardiac mortality , and total number of cardiac events were recorded . In the atorvastatin group , hsCRP and SAA values on the 5th day and in the 6th month compared to the first 24 h were significantly lower than those of the control group ( P < 0.0001 ) . Mean LDL cholesterol level was significantly decreased in the atorvastatin group ( 55.7 ± 17.7 mg/dl ) , but there was no significant change in the control group at the 6th month . The frequency of heart failure during the inpatient period and angina , unstable angina pectoris , heart failure , and revascularization in the first 6 months were also significantly reduced in the atorvastatin group . Atorvastatin started in the first 24 h reduces inflammation and improves the prognosis during both the inpatient period and the first 6 months of clinical follow-up in ACS patients with low LDL cholesterol levels Context While the benefits of statins in the primary and secondary prevention of coronary artery disease are clear , the value of statin therapy in acute coronary syndromes is uncertain . Contribution Analyzing data from a large , international observational study of acute coronary syndromes , these investigators identified associations between statin use before and during acute coronary events and favorable outcomes . Caution s While these data suggest a potential benefit of statins during acute coronary events , trials are necessary to determine the most appropriate use of statins in the treatment of acute coronary events . The Editors Data from r and omized clinical trials support the efficacy of lipid-lowering medications , particularly statins , in the primary and secondary prevention of coronary artery disease ( 1 - 3 ) . The benefits of statins , however , were not readily apparent until after several months of therapy , suggesting that the drugs ' lipid-lowering capabilities were largely responsible . In vitro work has suggested that statins may have an abundance of pleiotropic effects ( 4 ) . These include modulation of inflammation , inhibition of platelet function and thrombosis , and enhancement of endothelial cell function . The demonstrated ability of statins to immediately affect basic pathophysiologic mechanisms has result ed in increased interest in their potential role in the setting of acute coronary syndromes . The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) trial found that early treatment with high-dose atorvastatin modestly reduced event rates of recurrent ischemia in statin-naive patients presenting with an acute coronary syndrome ( 5 ) . These observations , while intriguing , did not conclusively establish the role of statins in patients with acute coronary syndromes . In the MIRACL trial , the failure of statins to significantly affect more concrete trial end points ( for example , death or recurrent myocardial infa rct ion [ MI ] ) was disappointing . Whether this reflected a true lack of physiologic impact of early statin treatment or merely indicated that the study was underpowered to detect differences in these end points remains unclear . In a sub study using data from the Platelet Receptor Inhibition for Ischemic Syndrome Management ( PRISM ) trial in patients with acute coronary syndromes , patients already taking statins  had better short-term outcomes ( decreased risk for death or nonfatal MI ) than those not previously receiving statin therapy , unless statin therapy was discontinued in the hospital ( 6 ) . Initiation of statin therapy after the onset of an acute coronary syndrome appeared to be less effective than treatment with statins before symptom onset . Using data from the Global Registry of Acute Coronary Events ( GRACE ) project , a large , multinational , observational study of patients with acute coronary syndromes , we examined the association between previous statin therapy  , presentation characteristics of acute coronary syndromes , and hospital outcomes . We also examined the effect of early in-hospital statin therapy ( or withdrawal of statins ) on important hospital outcomes , including death or the development of recurrent MI or stroke . Methods Full details of the GRACE rationale and methods have been published elsewhere and are outlined below ( 7 - 9 ) . Site Selection The GRACE project is design ed to reflect an unbiased population of patients with acute coronary syndromes , regardless of geographic region . Currently , 94 hospitals located in 14 countries ( Argentina , Australia , Austria , Belgium , Brazil , Canada , France , Germany , Italy , New Zeal and , Pol and , Spain , the United Kingdom , and the United States ) are participating in this observational study . Patients entered in the registry must be at least 18 years of age and alive at the time of hospital presentation ; be admitted with an acute coronary syndrome as a presumptive diagnosis ( that is , have symptoms consistent with acute ischemia ) ; and have at least 1 of the following : electrocardiographic changes consistent with an acute coronary syndrome , serial increases in serum biochemical markers of cardiac necrosis , or documentation of coronary artery disease ( 7 - 9 ) . The qualifying acute coronary syndrome must not be precipitated by a significant noncardiovascular comorbid condition ( for example , trauma or surgery ) . To ensure the enrollment of an unbiased sample , the first 10 to 20 consecutive patients ( depending on each site 's patient volume ) are recruited from each site on a monthly basis . Where required , study investigators received approval from their local hospital ethics or institutional review board . Data Collection At each site , a trained coordinator collected data using a st and ardized case-report form . Data on demographic characteristics , medical history , presenting symptoms , duration of prehospital delay , biochemical and electrocardiographic findings , treatment practice s , and hospital outcome were collected . St and ardized definitions of all patient-related variables and clinical diagnoses were used . All cases were assigned to 1 of the following categories : ST-segment elevation MI , nonST-segment elevation MI , unstable angina , and other cardiac or noncardiac diagnoses that have been previously described ( 7 - 9 ) . St and ardized definitions were also used for selected hospital complications and outcomes . Patient Sample For the current study , patients who were subsequently found to have noncardiac or other cardiac ( nonacute coronary syndrome ) primary diagnoses and those who transferred into or out of GRACE registry hospitals were excluded from further consideration . Treatments defined as previous use were those taken by the patient on a long-term basis at home and within 7 days of the presenting event , based on the review of information contained in medical records and abstract ed by trained study physicians and nurses . Treatments received in the hospital ( within the first 24 hours or thereafter ) were categorized as within hospital . Agents prescribed for use after discharge from participating hospitals were categorized as at discharge . Patient treatment categories were defined according to the following groupings : no previous treatment with statins and no treatment with statins during hospitalization , no previous therapy with statins but statin therapy  instituted during hospitalization , previous therapy with statins and statin therapy continued during hospitalization , and previous  therapy with statins but statin therapy not continued during the index hospitalization . Statistical Analysis We used the chi-square tests for discrete variables to analyze differences in demographic and clinical characteristics , treatment practice s , clinical presentation ( ST-segment elevation vs. nonST-segment elevation , large infa rct [ creatine phosphokinase level > 2 times the upper limit of normal ] vs. small infa rct ) , subsequent diagnosis ( ST-segment elevation MI , nonST-segment elevation MI , unstable angina ) , and hospital complications ( death , congestive heart failure or pulmonary edema , cardiogenic shock , stroke , ventricular tachycardia or ventricular fibrillation , and cardiac arrest ) in relation to statin use . The Wilcoxon rank-sum test was used to analyze differences between respective comparison groups for continuous variables . While controlling for potentially confounding variables , we performed multivariate regression analyses to examine the association between previous statin therapy and hospital presentation ( ST-segment elevation vs. no ST-segment elevation , creatine phosphokinase level 2 times normal vs. creatine phosphokinase level < 2 times the upper limit of normal ) , as well as any association between previous or in-hospital statin therapy and hospital outcomes ( death , recurrent MI or MI after 24 hours , and stroke ) or a composite end point of all 3 outcomes . C and i date variables for inclusion in the regression models evaluating previous statin use and hospital presentation included patient age , sex , smoking status , diabetes , history of vascular disease ( previous MI , stroke , positive angiogram , peripheral vascular disease , percutaneous coronary intervention , or coronary artery bypass graft surgery ) , hypertension , hyperlipidemia , and previous therapies ( aspirin , angiotensin-converting enzyme [ ACE ] inhibitors , -blockers , and other lipid-lowering agents ) . C and i date variables for regression models evaluating previous or in-hospital statin use and hospital outcomes included all of the previously listed characteristics plus characteristics present at the time of hospital admission ( heart rate , systolic blood pressure , Killip class , ST-segment elevation or left bundle-branch block pattern , and positive cardiac enzymes ) and receipt of in-hospital therapies ( aspirin and other antiplatelet agents , -blockers , unfractionated heparin , low-molecular-weight heparin , glycoprotein IIb/IIIa inhibitors , cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass graft surgery ) . C and i date variables possibly associated with the outcomes of interest ( P < 0.25 after univariate analysis ) were included in the multivariate models . Variables for which the P value exceeded 0.05 were eliminated in a stepwise fashion so that only those that had a statistically significant association with the outcome of interest were included in the final regression models . Because of their clinical relevance and potential importance , age , sex , and history of hyperlipidemia were retained in the final multivariable models for clinical outcomes regardless of statistical significance . Final models were evaluated for goodness of fit by the HosmerLemeshow test . Because between-hospital variation in use of statin treatment could be considerable and potentially affect our study results , we adjusted for hospital r and om effects on the observed outcomes . We used a generalized estimating equation modeling technique , assuming patients were repeated measures within each hospital . Variable Early initiation of statin therapy in acute coronary syndrome patients has a favorable prognostic impact because of its anti-inflammatory and antithrombotic properties . In this study , we explored the effect of atorvastatin-loading , followed by intensive atorvastatin therapy , on clinical and biochemical outcomes in non-ST-segment-elevation acute coronary syndrome patients who were scheduled for percutaneous coronary intervention . We prospect ively enrolled 140 patients ( mean age , 56 ± 9 years , 68 % men ) . Once eligible , patients were r and omly assigned to receive either a moderate 20-mg daily dose of atorvastatin ( Group A ) or a 160-mg loading dose followed by an intensified 80-mg daily dose ( Group B ) . High-sensitivity C-reactive protein ( hs-CRP ) levels were recorded before and after intervention . Evaluation after 6 months included hs-CRP levels , left ventricular systolic function , and major adverse cardiac events . We found no significant difference between the 2 groups in regard to the interventional data . However , blood sampling after coronary intervention , and again 6 months later , revealed a significant decline in mean hs-CRP level among Group B patients ( P < 0.001 ) . Moreover , patients in Group B manifested a higher left ventricular ejection fraction than did patients in Group A ( P < 0.05 ) . After 6 months , we found no significant difference between groups in the incidence of major adverse cardiac events . We conclude that intensive atorvastatin therapy in non-ST-segment-elevation acute coronary syndrome patients is associated with lower hs-CRP levels and with higher left ventricular ejection fraction after 6 months , with no significant impact on adverse cardiac events Background Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome ( ACS ) . The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear . The aim of our study was , therefore , to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS . Methods The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were r and omized at admission to fluvastatin 80 mg ( N = 78 ) or placebo ( N = 78 ) . Study medication was administered immediately after r and omization and then once daily for 30 days ; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75 % in the fluvastatin group and 78 % in the placebo group were on statin therapy . Results We did not demonstrate any difference between groups in the level of C-reactive protein , interleukin 6 , and pregnancy-associated plasma protein A on Day 2 and Day 30 ( primary endpoint ) . Fluvastatin-therapy , however , significantly reduced one-year occurrence of major adverse cardiovascular events ( 11.5 % vs. 24.4 % , odds ratio ( OR ) 0.40 , 95 % CI 0.17 - 0.95 , P = 0.038 ) . This difference was caused mainly by reduction of recurrent symptomatic ischemia ( 7.7 % vs. 20.5 % , OR 0.32 , 95 % CI 0.12 - 0.88 , P = 0.037 ) . Conclusions This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability . Fluvastatin therapy was , however , safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.Trial registration INTRODUCTION Acute coronary syndrome ( ACS ) is an important cause of mortality and significant personal and financial costs . Cardiac rehabilitation ( CR ) programs have shown positive effects in reducing cardiovascular mortality and improving functional capacity . However , adherence is low and appears to be influenced by psychosocial factors , such as patients ' cognitions and emotional state . The objective was to evaluate the efficacy of a brief in-hospital psychological intervention to promote cognitive and emotional adaptation after ACS . METHODS One hundred and twenty-one patients with ACS , admitted to a coronary care unit in a central hospital , were r and omized to an experimental group ( EG , n=65 ) and a control group ( CG , n=56 ) . Portuguese versions of the HADS and BIPQ  were used to measure emotional well-being and illness cognitions . Two 1 h 15 min sessions were conducted 2 - 3 days after hospital admission , and a 20-minute follow-up session took place one month after discharge . Patients were assessed at four different time points : pre-test , post-test , and at 1- and 2-month follow-up . RESULTS The intervention had significant effects on anxiety , depression and illness cognitions . Anxiety and depression were significantly reduced and illness cognitions improved significantly in the EG compared to the control group . For the EG , these changes were maintained or enhanced at 1- and 2-month follow-up , whereas for the CG there was a deterioration in psychosocial adjustment . CONCLUSIONS These results indicate that a brief psychological intervention program delivered during hospitalization for ACS and combined with st and ard medical care can have positive effects in terms of psychosocial outcomes that have proven impact on cardiac rehabilitation and prognosis Background Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture , which can lead to the development of acute coronary syndrome ( ACS ) . Elevated levels of serum inflammatory markers such as C-reactive protein ( CRP ) represent independent risk factors for further cardiovascular events . Recent evidence indicates that in addition to lowering cholesterol levels , statins also decrease levels of inflammatory markers . Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were design ed for very early secondary prevention . To our knowledge , no controlled trials have evaluated the potential benefits of statin therapy , beginning immediately at the time of hospital admission . A previous pilot study performed by our group focused on early initiation of cerivastatin therapy . We demonstrated a highly significant reduction in levels of inflammatory markers ( CRP and interleukin-6 ) . Based on these preliminary findings , we are conducting a clinical trial to evaluate the efficacy of another statin , fluvastatin , as an early intervention in patients with ACS . Methods The FACS-trial ( Fluvastatin in the therapy of Acute Coronary Syndrome ) is a multicenter , r and omized , double-blind , placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission . The study will enroll 1,000 participants admitted to hospital for ACS ( both with and without ST elevation ) . The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers ( CRP and interleukin-6 ) and on pregnancy associated plasma protein A ( PAPP-A ) . A combined secondary endpoint is 30-day and one-year occurrence of death , nonfatal myocardial infa rct ion , recurrent symptomatic ischemia , urgent revascularization , and cardiac arrest . Conclusion The primary objective of the FACS trial is to demonstrate that statin therapy , when started immediately after hospital admission for ACS , results in reduction of inflammation and improvement of prognosis . This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins BACKGROUND Statin pretreatment before percutaneous coronary intervention ( PCI ) is associated with a reduced incidence of short-term adverse events and periprocedural myocardial infa rct ion ( MI ) . However , the long-term effects of statin pretreatment have not been evaluated . METHODS Consecutive 445 patients with acute coronary syndrome ( ACS ) who underwent PCI were r and omly assigned to receive no statin treatment before PCI ( control group , n=220 ) or to receive 40 mg rosuvastatin loading before PCI ( rosuvastatin group , n=225 ) . The incidence of major adverse cardiac events ( MACE ) , including cardiac death , non-fatal MI , non-fatal stroke , and any ischemia-driven revascularization , was assessed after 12 months . RESULTS During 11±3 months of follow-up , MACE occurred in 20.5 % of patients in the control group and 9.8 % of patients in the rosuvastatin group ( p=0.002 ) . The Kaplan-Meier curves showed that the incidence of death and non-fatal MI was significantly greater in the control group than in the rosuvastatin group ( hazard ratio , 3.71 ; p=0.021 ) . High-sensitivity C-reactive protein levels were less elevated in the rosuvastatin group than in the control group at 24 h after PCI . Multivariate analysis revealed that rosuvastatin loading was an independent predictor of a reduction in the risk of MACE at 12 months ( odds ratio , 0.5 ; p=0.006 ) . CONCLUSIONS High dose rosuvastatin loading before PCI significantly improved 12-month clinical outcomes in patients with ACS who underwent an early invasive strategy Background —Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome ( ACS ) . We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol ( LCL-C ) lowering . The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS . Methods and Results —Seventy patients with ACS were enrolled . All patients underwent emergency coronary angiography and percutaneous coronary intervention ( PCI ) .  They were r and omized to intensive lipid-lowering therapy ( n=35 ; atorvastatin 20 mg/d ) or control ( n=35 ) groups after PCI . Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients ( atorvastatin , n=24 ; control , n=24 ) . LDL-C level was significantly decreased by 41.7 % in the atorvastatin group compared with the control group , in which LDL-C was increased by 0.7 % ( P<0.0001 ) . Plaque volume was significantly reduced in the atorvastatin group ( 13.1±12.8 % decrease ) compared with the control group ( 8.7±14.9 % increase ; P<0.0001 ) . Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level ( R=0.456 , P=0.0011 ) and percent LDL-C reduction ( R=0.612 , P<0.0001 ) , even in patients with baseline LDL-C < 125 mg/dL. Conclusions —Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS . Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction , even in patients with low baseline OBJECTIVES This study sought to determine if in addition to st and ard preventive measures on-admission , high-dose rosuvastatin exerts a protective effect against contrast-induced acute kidney injury ( CI-AKI ) . BACKGROUND Patients with acute coronary syndrome ( ACS ) are at high risk for CI-AKI , and the role of statin pre-treatment in preventing renal damage remains uncertain . METHODS Consecutive statin-naïve non-ST elevation ACS patients scheduled to undergo early invasive strategy were r and omly assigned to receive rosuvastatin ( 40 mg on admission , followed by 20 mg/day ; statin group n = 252 ) or no statin treatment ( control group n = 252 ) . CI-AKI was defined as an increase in creatinine concentration of ≥0.5 mg/dl or ≥25 % above baseline within 72 h after contrast administration . RESULTS The incidence of CI-AKI was significantly lower in the statin group than in controls ( 6.7 % vs. 15.1 % ; adjusted odds ratio : 0.38 ; 95 % confidence interval [ CI ] : 0.20 to 0.71 ; p = 0.003 ) . The benefits against CI-AKI were consistent , even applying different CI-AKI definition criteria and in all the pre-specified risk categories . The 30-day incidence of adverse cardiovascular and renal events ( death , dialysis , myocardial infa rct ion , stroke , or persistent renal damage ) was significantly lower in the statin group ( 3.6 % vs. 7.9 % , respectively ; p = 0.036 ) . Moreover , statin treatment given on admission was associated with a lower rate of death or nonfatal myocardial infa rct ion at 6 month follow-up ( 3.6 % vs. 7.2 % , respectively ; p = 0.07 ) . CONCLUSIONS High-dose rosuvastatin given on admission to statin-naïve patients with ACS who are scheduled for an early invasive procedure can prevent CI-AKI and improve short-term clinical outcome . ( Statin Contrast Induced Nephropathy Prevention [ PRATO-ACS ] ; NCT01185938 ) BACKGROUND The Global Registry of Acute Coronary Events (GRACE)-a prospect i ve , multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was design ed to improve the quality of care for patients with an ACS . Exp and ed GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practice s to an international reference cohort . METHODS We describe the objectives ; study design ; study and data management ; and the characteristics , management , and hospital outcomes of patients > or = 18 years old enrolled with a presumptive diagnosis of ACS . RESULTS From 2001 to 2007 , 31,982 patients were enrolled at 184 hospitals in 25 countries ; 30 % were diagnosed with ST-segment elevation myocardial infa rct ion , 31 % with non-ST-segment myocardial infa rct ion , 26 % with unstable angina , and 12 % with another cardiac/noncardiac final diagnosis . The median age was 65 ( interquartile range 55 - 75 ) years ; 24 % were > 75 years old , and 33 % were women . In general , increases were observed over time across the spectrum of ACS ( 1 ) in the use in the first 24 hours and at discharge of aspirin , clopidogrel , beta-blockers , and angiotensin-converting enzyme inhibitors/receptor blockers ; ( 2 ) in the use at discharge of statins ; ( 3 ) in the early use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin ; and ( 4 ) in the use of cardiac catheterization and percutaneous coronary intervention . An increase in the use of primary percutaneous coronary intervention and a similar decrease in the use of fibrinolysis in ST-segment elevation myocardial infa rct ion were also seen . CONCLUSIONS Over the course of 7 years , general increases in the use of evidence -based therapies for ACS patients were observed in the exp and ed GRACE BACKGROUND The recent North American and European practice guidelines in patients with non-ST-segment elevation acute coronary syndrome ( nSTE ACS ) recommend glycoprotein IIb/IIIa ( GpIIb-IIIa ) inhibition in patients undergoing an early invasive treatment strategy . However , the guidelines are not explicit regarding the timing of initiation of GpIIb-IIIa antagonists , and there is marked variation in clinical practice regarding their use . STUDY DESIGN The EARLY ACS trial will enroll 10,500 patients in a prospect i ve , r and omized , double blind , international , multicenter investigation of early eptifibatide compared with placebo ( with provisional eptifibatide in the catheterization laboratory ) in patients with high-risk nSTE ACS in whom an invasive strategy is planned no sooner than the next calendar day . The primary efficacy end point is the 96-hour composite of all-cause mortality , nonfatal myocardial infa rct ion , recurrent ischemia requiring urgent revascularization , or need for thrombotic bailout with GpIIb-IIIa inhibitor during percutaneous coronary intervention . The key secondary end point is the composite of death or nonfatal myocardial infa rct ion within 30 days of enrollment . IMPLICATION S The EARLY ACS trial will be the largest study to date to evaluate the utility of early GpIIb-IIIa inhibition in patients with nSTE ACS in whom an invasive approach is planned . This trial will provide important evidence regarding the benefit of initiating eptifibatide early after presentation with high-risk ACS versus delayed provisional use after coronary angiography . Furthermore , it will explore the ability of biomarkers to identify high-risk patients who may benefit from such an early aggressive approach CONTEXT Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome ( ACS ) event affect clinical outcome . OBJECTIVE To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS . DESIGN , SETTING , AND PARTICIPANTS International , r and omized , double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter ( n = 2265 ) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin ( n = 2232 ) , who were enrolled in phase Z of the A to Z trial between December 29 , 1999 , and January 6 , 2003 . MAIN OUTCOME MEASURE The primary end point was a composite of cardiovascular death , nonfatal myocardial infa rct ion , readmission for ACS , and stroke . Follow-up was for at least 6 months and up to 24 months . RESULTS Among the patients in the placebo plus simvastatin group , the median low-density lipoprotein ( LDL ) cholesterol level achieved while taking placebo was 122 mg/dL ( 3.16 mmol/L ) at 1 month and was 77 mg/dL ( 1.99 mmol/L ) at 8 months while taking 20 mg/d of simvastatin . Among the patients in the simvastatin only group , the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL ( 1.76 mmol/L ) and was 63 mg/dL ( 1.63 mmol/L ) at 8 months while taking 80 mg/d of simvastatin . A total of 343 patients ( 16.7 % ) in the placebo plus simvastatin group experienced the primary end point compared with 309 ( 14.4 % ) in the simvastatin only group ( 40 mg/80 mg ) ( hazard ratio [ HR ] , 0.89 ; 95 % confidence interval [ CI ] 0.76 - 1.04 ; P = .14 ) . Cardiovascular death occurred in 109 ( 5.4 % ) and 83 ( 4.1 % ) patients in the 2 groups ( HR , 0.75 ; 95 % CI , 0.57 - 1.00 ; P = .05 ) but no differences were observed in other individual components of the primary end point . No difference was evident during the first 4 months between the groups for the primary end point ( HR , 1.01 ; 95 % CI , 0.83 - 1.25 ; P = .89 ) , but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group ( HR , 0.75 ; 95 % CI , 0.60 - 0.95 ; P = .02 ) . Myopathy ( creatine kinase > 10 times the upper limit of normal associated with muscle symptoms ) occurred in 9 patients ( 0.4 % ) receiving simvastatin 80 mg/d , in no patients receiving lower doses of simvastatin , and in 1 patient receiving placebo ( P = .02 ) . CONCLUSIONS The trial did not achieve the prespecified end point . However , among patients with ACS , the early initiation of an aggressive simvastatin regimen result ed in a favorable trend toward reduction of major cardiovascular events OBJECTIVES The objective of this study was to evaluate whether the regressive effects of aggressive lipid-lowering therapy with atorvastatin on coronary plaque volume ( PV ) in patients with acute coronary syndrome ( ACS ) are generalized for other statins in multicenter setting . BACKGROUND A previous single-center study reported beneficial regressive effects of atorvastatin in patients with ACS on PV of the nonculprit site by intravascular ultrasound ( IVUS ) evaluation . The effect of statins other than atorvastatin on PV has not been evaluated in the setting of ACS . METHODS The JAPAN-ACS ( Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ) study was a prospect i ve , r and omized , open-label , parallel group study with blind end point evaluation conducted at 33 centers in Japan . A total of 307 patients with ACS undergoing IVUS-guided percutaneous coronary intervention were r and omized , and 252 patients had evaluable IVUS examinations at baseline and 8 to 12 months ' follow-up . Patients were r and omly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin . The primary end point was the percentage change in nonculprit coronary PV . RESULTS The mean percentage change in PV was -16.9 + /- 13.9 % and -18.1 + /- 14.2 % ( p = 0.5 ) in the pitavastatin and atorvastatin groups , respectively , which was associated with negative vessel remodeling . The upper limit of 95 % confidence interval of the mean difference in percentage change in PV between the 2 groups ( 1.11 % , 95 % confidence interval : -2.27 to 4.48 ) did not exceed the pre-defined noninferiority margin of 5 % . CONCLUSIONS The administration of pitavastatin or atorvastatin in patients with ACS equivalently result ed in significant regression of coronary PV ( Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ; NCT00242944 ) This study was design ed to evaluate how new treatment guidelines of acute coronary syndrome ( ACS ) without ST elevation have been implemented in clinical practice especially in diabetic patients . A prospect i ve follow-up was performed on 501 consecutive patients with suspected ACS without ST elevation admitted to nine hospitals in Finl and between 15 January and 11 March 2001 . The study group included 143 ( 29 % ) diabetic patients . Their risk profile was more severe than in non-diabetic patients ; ST-depression on admission electrocardiography 57 versus 38 % ; P<0.0001 , elevated troponin levels 66 versus 56 % ; P<0.05 . Six months composite incidence of death , new myocardial infa rct ion ( MI ) , refractory angina or readmission for unstable angina was 39 % in diabetic patients and 20 % in non-diabetic patients ( P<0.0001 ) . In spite of this more severe risk profile , glycoprotein ( GP ) IIb/IIIa receptor antagonists and statins were used with similar frequency in non-diabetic and diabetic patients ( 15 vs. 19 and 48 vs. 54 % , respectively ; P = NS for both ) . In diabetic patients mean delay for in hospital coronary angiography was longer ( 6.4 vs. 4.2 days , P<0.05 ) and it was performed less often ( 32 vs. 45 % P<0.05 ) . Our results show that diabetic patients with ACS have higher risk profile and worse outcome than non-diabetic patients . Despite their indisputable benefits in diabetic patients , statins , GP IIb/IIIa receptor antagonists and invasive strategy were underused or often neglected . Further education is needed to change attitudes and to better implement new guidelines into clinical practice BACKGROUND Inflammation has been suggested as a factor in the initiation and maintenance of  atrial fibrillation ( AF ) . Several observational studies have suggested that statins , presumably through their anti-inflammatory properties , decrease the risk of AF . METHODS We analyzed 2 large , r and omized trials , PROVE IT-TIMI 22 and phase Z of the A to Z trial , which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up . We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy . From each trial , patients experiencing the onset of AF during follow-up were identified from the adverse event reports . RESULTS Neither study showed a decreased AF risk with higher-dose statin . In PROVE IT-TIMI 22 , 2.9 % versus 3.3 % in the high- versus st and ard-dose statin therapy , respectively , experienced the onset of AF over 2 years ( OR 0.86 , 95 % CI 0.61 - 1.23 , P = .41 ) . In A to Z , rates were 1.6 % versus 0.99 % , respectively ( OR 1.58 , 95 % CI 0.92 - 2.70 , P = .096 ) . In both trials , C-reactive protein levels ( plasma or serum ) tended to be higher among patients experiencing the onset of AF . CONCLUSION Our r and omized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with st and ard dose statin treatment OBJECTIVE To examine the relationship of baseline tissue plasminogen activator ( t-PA ) to early cardiovascular risk after an acute coronary syndrome , and the effect of intensive statin therapy . METHODS We measured plasma t-PA in 2860 of the 3086 ( 93 % ) subjects in the MIRACL study , an international r and omized trial of atorvastatin 80 mg daily versus placebo in patients with acute coronary syndromes . The relationship of t-PA to death , non-fatal acute myocardial infa rct ion , cardiac arrest , or worsening angina over 16 weeks was assessed by Cox Proportional Hazards . D-dimer was measured in a r and om sample of 395 subjects . RESULTS Higher baseline t-PA was significantly related to the risk of recurrent events ( HR=1.25 , p=0.0014 ) . This relationship was unaffected by adjustment for age , sex , troponin , hsCRP , and lipids ( HR=1.17 , p=0.029 ) , but was attenuated by adjustment including body mass index and smoking ( HR=1.14 , p=0.08 ) . D-dimer and t-PA concentrations were not related . Atorvastatin reduced the risk of recurrent events , but did not affect t-PA or D-dimer concentrations or the relationship of t-PA to outcomes . CONCLUSION In patients with acute coronary syndromes , increasing t-PA concentration was related to a higher early risk of recurrent events , paradoxically reflecting impaired endogenous fibrinolysis . This relationship is due in part to the association of t-PA with age , body mass index and smoking . Although statins lower the risk of recurrent events after acute coronary syndromes , it is unlikely that this benefit is achieved through thrombolytic and fibrinolytic pathways
Based on moderate quality evidence , due to concerns about risk of bias and imprecision , initiation of statin therapy within 14 days following ACS does not reduce death , myocardial infa rct ion , or stroke up to four months , but reduces the occurrence of unstable angina at four months following ACS .
Serious side effects were rare
BACKGROUND The early period following the onset of acute coronary syndrome ( ACS ) represents a critical stage of coronary heart disease , with a high risk of recurrent events and deaths .
The short-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from ACS are unclear .
This is an up date of a review previously published in 2011 .
OBJECTIVES To assess the effects , both harms and benefits , of early administered statins in patients with ACS , in terms of mortality and cardiovascular events .