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. Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696] 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). Prognosis of Patients With Familial Hypercholesterolemia After Acute Coronary Syndromes Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study Urinary albumin concentration and long-term cardiovascular risk in acute coronary syndrome patients: a PROVE IT-TIMI 22 substudy Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial) 12-month follow-up results of high dose rosuvastatin loading before percutaneous coronary intervention in patients with acute coronary syndrome. The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy. Design and rationale of a study in Asia of atorvastatin pretreatment in patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Impact of gender difference on long-term outcomes of percutaneous coronary intervention for coronary artery disease in patients under statin treatment Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. Early high-dose rosuvastatin and cardioprotection in the protective effect of rosuvastatin and antiplatelet therapy on contrast-induced acute kidney injury and myocardial damage in patients with acute coronary syndrome (PRATO-ACS) study. The effect of Mediterranean diet on the risk of the development of acute coronary syndromes in hypercholesterolemic people: a case–control study (CARDIO2000) The effect of different doses of fluvastatin on inflammatory markers in the early phase of acute coronary syndrome. The influence of low dose atorvastatin on inflammatory marker levels in patients with acute coronary syndrome and its potential clinical value. [The changes of electrocardiogram and impact of early invasive strategy in patients with acute coronary syndromes without ST-segment elevation]. 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 [The relationship between TIMI (thrombolysis in myocardial infarction) risk score and efficacy of conservative or interventional strategy in patients with non-ST-segment elevation acute coronary syndromes]. [The effect of early invasive strategy on early and late outcomes in high-risk non-ST-segment elevation acute coronary syndromes]. 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 Lipoprotein-Associated Phospholipase A2 and Its Association With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction) Trial
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 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 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 : Patients with heterozygous familial hypercholesterolemia ( FH ) and coronary heart disease have high mortality rates . However , in an era of high-dose statin prescription after acute coronary syndrome ( ACS ) , the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated . We compared coronary event rates between patients with and without FH after ACS . METHODS : We studied 4534 patients with ACS enrolled in a multicenter , prospect i ve cohort study in Switzerl and between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions : the American Heart Association definition , the Simon Broome definition , and the Dutch Lipid Clinic definition . We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infa rct ion and adjusted for age , sex , body mass index , smoking , hypertension , diabetes mellitus , existing cardiovascular disease , high-dose statin at discharge , attendance at cardiac rehabilitation , and the GRACE ( Global Registry of Acute Coronary Events ) risk score for severity of ACS . RESULTS : At the 1-year follow-up , 153 patients ( 3.4 % ) had died , including 104 ( 2.3 % ) of fatal myocardial infa rct ion . A further 113 patients ( 2.5 % ) experienced nonfatal myocardial infa rct ion . The prevalence of FH was 2.5 % with the American Heart Association definition , 5.5 % with the Simon Broome definition , and 1.6 % with the Dutch Lipid Clinic definition . Compared with patients without FH , the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses , although patients with FH were > 10 years younger . However , after multivariable adjustment including age , the risk was greater in patients with FH than without , with an adjusted hazard ratio of 2.46 ( 95 % confidence interval , 1.07–5.65 ; P=0.034 ) for the American Heart Association definition , 2.73 ( 95 % confidence interval , 1.46–5.11 ; P=0.002 ) for the Simon Broome definition , and 3.53 ( 95 % confidence interval , 1.26–9.94 ; P=0.017 ) for the Dutch Lipid Clinic definition . Depending on which clinical definition of FH was used , between 94.5 % and 99.1 % of patients with FH were discharged on statins and between 74.0 % and 82.3 % on high-dose statins  . CONCLUSIONS : Patients with FH and ACS have a > 2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins 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 Albuminuria has been shown to be associated with mortality and cardiovascular events , independent of traditional cardiovascular risk factors . This suggests that albuminuria may not just represent glomerular damage , but may be a marker of more diffuse endothelial dysfunction . We investigated the relationship between urinary albumin levels after an acute coronary syndrome and cardiovascular outcomes in  statin treated subjects after acute coronary syndromes ( ACS ) . Furthermore we assessed the effect of intensive statin treatment on albuminuria among patients in the PROVE IT-TIMI 22 trial , in which patients who had been hospitalized with ACS were r and omized to pravastatin 40 mg ( st and ard therapy ) or atorvastatin 80 mg daily ( intensive therapy ) . In univariate analyses , increasing urine albumin concentration was associated with increased risk of myocardial infa rct ion , stroke , heart failure , and composite of death , myocardial infa rct ion and stroke at 2 years . However , in a multivariable model containing traditional cardiovascular risk factors , albuminuria was not an independent predictor of the primary PROVE IT endpoint of death , myocardial infa rct ion , unstable angina , revascularization and stroke , and was only an independent predictor of all-cause mortality at urinary albumin concentration > 300 mcg/ml . There was no significant change in urinary albumin concentration from enrolment to end of study in either the st and ard or intensive statin therapy groups , and no significant difference between treatment groups . Our results suggest that after an acute coronary syndrome in statin treated patients , microalbuminuria may reflect traditional cardiovascular risk factor burden and offer little prognostic information independent of those factors 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 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 The A-to-Z Trial is an ongoing international , multicenter , r and omized study design ed to investigate 2 issues concerning contemporary care of patients with acute coronary syndromes ( ACS ) . The first issue is whether the use of low-molecular-weight heparin versus unfractionated heparin affects outcomes and safety when used as a therapy adjunctive to baseline treatment with tirofiban and aspirin in patients with non-ST-elevation ( nSTE ) ACS . The second issue is whether early use of an aggressively dosed statin is superior to a current trial-based " accepted care " regimen of a lower-dose statin started 3 to 6 months after an acute event . METHODS The study is conceptually and functionally divided into 2 sequential parts-the " A " Aggrastat and " Z " Zocar phases . The primary A-phase end point is a composite of all-cause mortality , myocardial infa rct ion ( MI ) , and documented refractory ischemia at 7 days .  Both nSTE-ACS patients from the A phase and patients with ST-elevation ACS who meet specific risk criteria are eligible to enter the subsequent " Z " ( Zocor ) chronic phase ( Z phase ) . The primary end point of the Z phase is a composite of cardiovascular death , MI , readmission for ACS , and stroke . The trial will continue until 970 primary events have occurred in the Z-phase population . CONCLUSION This trial is evaluating 2 temporally connected sequences of phamacotherapy for ACS . At completion , trial results will provide definitive evidence regarding efficacy and safety of early , intensive statin therapy and better define the role of low-molecular-weight heparin in patients with nSTE ACS BACKGROUND Studies in Western population s have shown the benefits of pretreatment with atorvastatin in preventing cardiovascular events in patients , including those with acute coronary syndromes ( ACS ) , undergoing percutaneous coronary intervention ( PCI ) . However , data concerning the value of such therapy in Asian patients are limited . The primary objective of the present study is to evaluate the efficacy of atorvastatin in reducing cardiovascular outcomes in Asian patients with non-ST-segment elevation (NSTE)-ACS following hospital admission for early PCI ( within 72 h of the onset of symptoms ) . Secondary objectives are to assess the effects of atorvastatin on cardiac biomarker levels , and the safety and tolerability profile of atorvastatin . METHODS This study is a prospect i ve , multicenter , open-label trial design ed to enroll 350 statin-naïve patients with NSTE-ACS scheduled for PCI in China and the Republic of Korea . Patients are r and omized to either usual care or atorvastatin treatment groups , with patients in both treatment groups receiving usual care including atorvastatin 40 mg/day for 30 days post-PCI . Patients in the atorvastatin group receive additional doses of atorvastatin 80 mg at 12 h pre-PCI and 40 mg at 2 h pre-PCI . The primary end point is the incidence of major adverse cardiac events ( death , myocardial infa rct ion , and target vessel revascularization ) at 30 days post-PCI . CONCLUSIONS The present study will provide valuable insights into whether the benefits of atorvastatin pretreatment extend to Asian patients with ACS undergoing interventions . Enhanced treatment of these patients will be an important contribution towards alleviating the increasing burden of cardiovascular disease in Asian countries BACKGROUND Following acute coronary syndrome ( ACS ) , the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol ( LDL-C ) even within the setting of intensive statin treatment . Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab , a fully human monoclonal antibody to PCSK9 , improves cardiovascular outcomes after ACS . DESIGN This Phase 3 study will r and omize approximately 18,000 patients to receive biweekly injections of alirocumab ( 75 - 150 mg ) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infa rct ion or unstable angina . Qualifying patients are treated with atorvastatin 40 or 80 mg daily , rosuvastatin 20 or 40 mg daily , or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria : LDL-C ≥ 70 mg/dL , non-high-density lipoprotein cholesterol ≥ 100 mg/dL , or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death , acute myocardial infa rct ion , hospitalization for unstable angina , or ischemic stroke . The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years , providing 90 % power to detect a 15 % hazard reduction . Adverse events of special interest include allergic events and injection site reactions . Interim analyses are planned when approximately 50 % and 75 % of the targeted number of primary end points have occurred . SUMMARY ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS The incidence of adverse outcomes after percutaneous coronary intervention ( PCI ) is higher in women than in men . Statins reduce the likelihood of cardiovascular events arising in patients with coronary artery disease ( CAD ) , but the impact of gender difference on long-term outcomes of PCI for CAD under statin treatment has not been established . We prospect ively enrolled 3,580 consecutive patients with CAD who were treated by PCI at our institution between 2000 and 2011 . Among these , 2,009 ( 43.9 % ; male , n = 1619 ; female , n = 390 ) were under statin therapy at the time of PCI . We evaluated the incidence of major adverse cardiac events ( MACE ) including all-cause death and acute coronary syndrome ( ACS ) . Age was significantly more advanced and the prevalences of hypertension and chronic kidney disease were higher among the female , than the male patients . Low-density lipoprotein cholesterol levels were significantly higher in women than in men ( 111.5 ± 38.9 vs. 107.5 ± 3 3.9 mg/dL , p = 0.04 ) . During a median follow-up period of 6.3 years , MACE that occurred in 336 ( 16.7 % ) patients included 206 ( 10.2 % ) with all-cause death and 154 ( 7.7 % ) with ACS . The cumulative rate of MACE tended to be higher in women than in men but the difference did not reach significance ( 19.7 vs. 16.0 % ; p = 0.08 , log-rank test ) . Multivariable Cox regression analysis showed that being female was not associated with MACE after adjusting for age ( HR 1.22 ; 95 % CI 0.94–1.57 ; p = 0.13 ) and other variables ( HR 1.14 ; 95 % CI 0.86–1.49 ; p = 0.35 ) . Long-term clinical outcomes were comparable between male and female patients with coronary artery disease who were administered with statins and underwent PCI even though the baseline characteristics were worse among the females OBJECTIVES This study sought to investigate potential protective effects of atorvastatin in patients with acute coronary syndromes ( ACS ) undergoing percutaneous coronary intervention ( PCI ) . BACKGROUND R and omized studies have shown that pretreatment with atorvastatin may reduce periprocedural myocardial infa rct ion in patients with stable angina during elective PCI ; however , this therapy has not been tested in patients with ACS . METHODS A total of 171 patients with non-ST-segment elevation ACS were r and omized 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 infa rct ion , or unplanned revascularization ) . RESULTS 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 infa rct ion 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 ) . CONCLUSIONS 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 BACKGROUND There is a strong correlation between adverse clinical events and peak values of myocardial necrosis markers in non-ST-elevation acute coronary syndrome patients . In this clinical setting , high-dose statin treatment exerts acute beneficial effects against renal and myocardial damage . The aim of this report was to evaluate if , on admission , high-dose rosuvastatin can exert cardioprotective effects when administered in addition to high-dose clopidogrel . METHODS In the PRATO-ACS trial , 504 consecutive statin-naïve non-ST-elevation acute coronary syndrome patients scheduled for early invasive strategy and pretreated with high-dose clopidogrel  were r and omly assigned to rosuvastatin ( 40 mg on admission followed by 20 mg/d ; statin group , n = 252 ) or no statin treatment ( control group , n = 252 ) . Serial myocardial biomarker sample s were collected before and after angiography and /or percutaneous coronary intervention . The primary end point was the peak level of cardiac troponin I ( cTnI ) during the index event . RESULTS Statin-treated patients presented median cTnI peak values similar to controls ( 3.9 [ 0.6 - 12.8 ] vs 3.5 [ 1.2 - 11.9 ] ng/mL , respectively ; P = .60 ] ; no differences were found between the 2 groups in cTnI and creatine kinase-MB values at any time point , in either preangiography and postangiography peak values or their cumulative release . In patients su bmi tted to percutaneous coronary intervention , periprocedural myocardial infa rct ion occurred in 8 ( 4.7 % ) of 171 statin-treated and 7 ( 4.3 % ) of 162 control patients ( P = .87 ) . CONCLUSION In the PRATO-ACS trial , early high-dose rosuvastatin did not show cardioprotective effects when administered in addition to high-dose clopidogrel Background Hypercholesterolemia has been identified as a major risk factor for the development of coronary artery disease . The aim of this study was to assess the effect of a Mediterranean diet on the development of non-fatal acute coronary syndromes ( ACS ) in hypercholesterolemic people , with or without statin treatment . Methods During 2000–2001 , 848 r and omly selected patients with a first event of coronary heart disease and 1078 cardiovascular disease-free people , matched to the patients by sex , age and region , were studied . Treatment of hypercholesterolemia with statin and the adoption of a Mediterranean diet were recorded . Results Hypercholesterolemia was present in 534 ( 63 % ) out of 848 coronary patients and 399 ( 37 % ) out of 1078 control participants . One hundred and seventy-one ( 32 % ) of the hypercholesterolemic patients and 168 ( 42 % ) of the hypercholesterolemic control participants were treated with statins and also followed a Mediterranean diet . The analysis showed that the combination of a Mediterranean diet and  statin medical therapy is associated with an additional reduction of the coronary risk ( odds ratio = 0.57 , P < 0.01 ) , independently from cholesterol levels and the other cardiovascular factors . Conclusion The adoption of a Mediterranean diet by hypercholesterolemic people seems to reinforce the benefits from statin treatment on lipid levels and reduces the risk of developing ACS . However , it is hard to cl aim that our findings suggest causal evidence , and in order to explain the potential common mechanism between diet and statin treatment much remains to be learned BACKGROUND Inflammation promotes acute coronary syndromes ( ACS ) and ensuing clinical complications . It is well known that statins decrease the risk of coronary events and may benefit the stabilization of atherosclerotic plaque with their anti-inflammatory effects . We investigated the effects of different doses of fluvastatin on serum concentrations of high-sensitive C-reaction protein ( hs-CRP ) and tumor necrosis factor-alpha ( TNF-alpha ) in the early phase of ACS . METHODS We prospect ively r and omized 60 patients with ACS to 3 groups : ( 1 ) group A ( n=20 ) : were given routine therapy ; ( 2 ) group B ( n=20 ) : were administrated routine therapy with 40 mg/d oral fluvastatin ;  ( 3 ) group C ( n=20 ) : received routine therapy with 80 mg/d oral fluvastatin .  Twenty patients with stable coronary heart disease served as controls . The following-up period was 7 days . By immunoturbidimetric assay and ELISA methods the serum concentrations of hs-CRP and TNF-alpha were measured before and after therapy . RESULTS ( 1 ) The serum concentrations of hs-CRP and TNF-alpha in patients with ACS was significantly higher than those in the control group ( P<0.05 ) . ( 2 ) After 1 week of therapy , the serum concentrations of hs-CRP and TNF-alpha were significantly lower in group B and group C ( all P<0.01 ) , especially in group C. ( 3 ) The serum concentrations of hs-CRP and TNF-alpha did not correlate to the concentrations of TC , TG , LDL-C , or HDL-C. CONCLUSION Early fluvastatin intervention decreases dose-dependently the serum concentrations of hs-CRP and TNF-alpha of patients with ACS . The high-dose fluvastatin invention may play a stronger anti-inflammatory effect in ACS patients . The anti-inflammatory effect of fluvastatin may be beyond the lipid lowering BACKGROUND High-dose statins are used in acute coronary syndromes ( ACS ) to reduce inflammation . The aim of the study was the evaluation of the influence of low-dose atorvastatin ( 20 mg ) on selected inflammatory parameters and clinical outcomes after ACS . METHODS Seventy eight patients ( pts ) with ACS were r and omly divided into group A ( 39 pts ) taking atorvastatin , and group NA ( 39 pts ) not taking any statin for the following six weeks . C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , monocyte chemoattractant protein-1 ( MCP-1 ) and tumour necrosis factor alpha ( TNFa ) levels were measured on the first and the fifth days and six weeks after ACS . RESULTS There was no significant CRP and IL-6 level decrease in group A ( CRP--62 % ; IL-6 - 73 % ) or group NA ( CRP-44 % ; IL-6 - 62 % ) . There was also no significant change in TNFa levels . The MCP-1 level finally reached the level of significant difference ( p < 0.04 ) . Cardiovascular events ( MACE ) and the restenosis rates did not differ between the groups . CONCLUSIONS Low-dose atorvastatin does not have a significant influence on cooling down inflammation in ACS , and MCP-1 can be used as an early indicator of statin anti-inflammatory activity . Furthermore , it does not reduce MACE or restenosis rates despite its influence on MCP-1 levels OBJECTIVE To investigate the changes of electrocardiogram ( ECG ) and impact of early invasive strategy in patients with acute coronary syndrome ( ACS ) without ST-segment elevation . METHODS Five hundred and forty-five consecutive ACS patients without ST-segment elevation were r and omly assigned to early conservative treatment group and early invasive treatment group . The combined cardiovascular events , including cardiac death , nonfatal myocardial infa rct ion , nonfatal heart failure , and re-hospitalization due to recurrent ischemia angina , within 30 days and 6 months were analyzed and the effects of varied ECG changes and different intervention strategies on outcomes of patients were evaluated . RESULTS The incidences of each and combined cardiovascular events were higher in the patients with ST-segment depression than in those without ST-segment depression . ST-segment depression was one of independent predictive factors for an increase in cardiovascular events within 6 months ( OR 3.864 , 95 % CI : 1.668 approximately 9.451 , P < 0.001 ) . Early invasive strategy was associated with a lower rate of re-hospitalization due to recurrent ischemia angina within 30 days and a decreased incidence of combined cardiovascular events within 30 days and 6 months in comparison with the early conservative treatment group ( all P < 0.05 ) . Subgroup analysis implied that incidences of combined cardiovascular events within 30 days and 6 months decreased significantly only in patients with ST-segment depression treated with early invasive strategy , and no such benefit was seen in the patients without ST-segment depression . CONCLUSION ST-segment depression is an effective indicator for identifying those patients with non-ST segment elevation ACS most likely to benefit from early invasive strategy . Early invasive strategy markedly decreases the cardiovascular events in ACS patients with ST-segment depression than early conservative strategy 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 OBJECTIVE To investigate the relationship between thrombolysis in myocardial infa rct ion ( TIMI ) risk score and efficacy of different treatment strategies in patients with non-ST-segment elevation acute coronary syndromes ( NSTE-ACS ) . METHODS From Oct. 2001 to Oct. 2003 , 545 consecutive patients with NSTE-ACS were r and omly assigned to early conservative strategy ( n = 284 ) or early invasive strategy group ( n = 261 ) . The combined cardiovascular events ( a combination of cardiac death , nonfatal myocardial infa rct ion , nonfatal heart failure and re-hospital admission due to recurrent ischemia angina ) within 30 days and 6 months were analyzed and related to the TIMI risk score at admission . RESULTS Rehospitalization due to recurrent ischemia angina of 30 days and the combined cardiovascular events of 30 days and 6 months were significantly lower in early invasive strategy group ( 3.5 % , 10.0 % , 21.1 % ) compared with early conservative strategy group ( 8.1 % , 16.9 % , 28.2 % , all P < 0.05 ) . Subgroup analysis indicated early invasive strategy could significantly decrease the 30 d incidence of the combined end point events in patients with high TIMI risk score and the 6 months incidence of the combined end point events in patients with moderate and high TIMI risk score ( all P < 0.01 ) , but the incidence was similar between the two different strategies in patients with low TIMI risk score . CONCLUSIONS Early invasive strategy may significantly reduce combined cardiovascular events in NSTE-ACS patients with moderate and high TIMI risk score compared with early conservative strategy OBJECTIVE To investigate the effect of early invasive strategy on early and late outcomes in high-risk patients with non-ST-segment elevation acute coronary syndromes ( ACS ) . METHODS Five hundred and forty-five patients of ACS without ST-segment elevation were r and omly assigned to an  early conservative strategy  ( 284 cases ) or early invasive strategy group  ( 261 cases ) , who were enrolled consecutively from Oct. , 2001 to Oct. , 2003 . The combined cardiovascular events ( a combination of cardiac death , nonfatal myocardial infa rct ion , nonfatal heart failure and hospital readmission due to recurrent ischemic angina ) within 30 days and 6 months were analyzed and the effects of early invasive strategy on early and late outcomes in high-risk patients with increased TnI or hs-CRP levels were evaluated . RESULTS As compared with early conservative strategy , early invasive strategy lowered the rate of hospital readmission due to recurrent ischemic angina of 30 d and the combined cardiovascular events of 30 d and 6 months ( all P < 0.05 ) . Subgroup analysis indicated early invasive strategy could significantly decrease the incidences of the combined cardiovascular events of 30 d and 6 months and the hard end point events of 6 months in patients with increased TnI or hs-CRP levels ( all P < 0.01 ) , but no such changes could be seen in patients with normal TnI or hs-CRP levels , as compared with early conservative strategy . CONCLUSIONS Early invasive strategy decreases significantly cardiovascular events and improves the early and late outcomes in high-risk patients with increased TnI or hs-CRP levels 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 Background — Lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) is associated with the risk of cardiovascular ( CV ) events in population -based studies . The prognostic value of Lp-PLA2 in patients with acute coronary syndromes ( ACS ) has not been established . Methods and Results — Plasma levels of Lp-PLA2 activity were measured at baseline ( n=3648 ) and 30 days ( n=3265 ) in patients r and omized to atorvastatin 80 mg/d or pravastatin 40 mg/d after ACS in the PROVE IT-TIMI 22 ( PRavastatin Or atorVastatin  Evaluation and Infection Therapy – Thrombolysis In Myocardial Infa rct ion ) trial . The primary end point was death , myocardial infa rct ion , unstable angina , revascularization , or stroke ( mean follow-up 24 months ) . At baseline after ACS , the risk of recurrent CV events was similar across all quintiles of Lp-PLA2 activity ( Ptrend=0.88 ) . Overall , mean levels of Lp-PLA2 were lower at 30 days of follow-up than at baseline ( 35.7 versus 40.9 nmol · min−1 · mL−1 , P<0.001 ) . In particular , treatment with atorvastatin 80 mg/d was associated with a 20 % reduction in Lp-PLA2 activity ( P<0.001 ) , whereas Lp-PLA2 rose 3.6 % with pravastatin 40 mg/d ( P<0.001 ) . Patients with 30-day Lp-PLA2 activity in the highest quintile were at significantly increased risk of recurrent CV events compared with those in the lowest quintile ( 26.4 % versus 17.6 % , Ptrend=0.002 ) . After adjustment for cardiac risk factors , treatments , achieved low-density lipoprotein ( LDL ) , and C-reactive protein , Lp-PLA2 activity in the highest quintile remained independently associated with a higher risk of recurrent CV events ( adjusted hazard ratio 1.33 , 95 % confidence interval [ CI ] 1.01 to 1.74 ) . Conclusions — Lp-PLA2 is not useful for risk stratification when measured early after ACS . At 30 days , Lp-PLA2 activity is significantly lowered with high-dose statin therapy and is associated with an increased risk of CV events independent of C-reactive protein and LDL cholesterol levels
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 .