***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: AIMS Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 ( CYP ) 3A4-oxi date d statins such as simvastatin . We assessed the hypothesis that simvastatin , in contrast to CYP 2C9-metabolized fluvastatin , reduces clopidogrel-mediated platelet inhibition . METHODS We performed a r and omized , double-blind , double-dummy , two period crossover study in 13 patients with cerebral ischaemia ( 8F , 5 M ) , aged 64.1 ± 8.0 years ( mean ± SD ) . After a 14 day period in which all patients received 75 mg clopidogrel day(-1 ) , patients additionally received either 20 mg simvastatin day(-1 ) or 80 mg fluvastatin day(-1 ) for 14 days . Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days . Platelet aggregation , clopidogrel active metabolite ( CAM ) plasma concentrations and routine laboratory parameters including prothrombin time ( PT ) Quick percent value were assessed at baseline and following each treatment phase . RESULTS Clopidogrel  reduced platelet aggregation in all patients as expected . Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel . Simvastatin  decreased PT Quick percent value ( decrease from 109 ± 10.5 % to 103 ± 11 % , P < 0.05 ) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel . CONCLUSIONS Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation . After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2 Background —The antiplatelet effect of clopidogrel may be attenuated by short-term coadministration of lipophilic statins . We investigated whether the coadministration of atorvastatin for 5 weeks in patients with acute coronary syndromes ( ACS ) could affect the antiplatelet potency of clopidogrel . Methods and Results —Forty-five hypercholesterolemic patients with the first episode of an ACS were included in the study . Patients were r and omized to receive daily either 10 mg of atorvastatin ( n=21 ) or 40 mg of pravastatin ( n=24 ) . Thirty patients who underwent percutaneous coronary intervention ( PCI ) received a loading dose of 375 mg of clopidogrel , followed by 75 mg/d for at least 3 months . In the remaining 15 patients who refused to undergo PCI , clopidogrel therapy was not administered . Eight normolipidemic patients with the first episode of an ACS were also included and received only clopidogrel . The serum levels of soluble CD40L and the adenosine 5′-diphosphate– or thrombin receptor activating peptide-14–induced platelet aggregation , as well as P-selectin and CD40L surface expression , were studied at baseline ( within 30 minutes after admission ) and 5 weeks later . Neither atorvastatin nor pravastatin significantly influenced the clopidogrel-induced inhibition of platelet activation , nor did clopidogrel influence the therapeutic efficacy of atorvastatin . Conclusions —Atorvastatin does not affect the antiplatelet potency of clopidogrel when coadministered for 5 weeks in ACS patients OBJECTIVES This study sought to evaluate the clinical relevance of potential clopidogrel drug-drug interactions . BACKGROUND Some studies have demonstrated that statins and calcium-channel blockers ( CCBs ) may attenuate the pharmacodynamic effects of clopidogrel . METHODS The TRITON-TIMI 38 ( Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infa rct ion 38 ) enrolled 13,608 patients with an acute coronary syndrome ( ACS ) and planned percutaneous coronary intervention ( PCI ) , and r and omized them to clopidogrel or prasugrel . Use of a statin or CCB was left to the discretion of the treating physician . A multivariable Cox model with propensity score was employed to evaluate the association between statin or CCB use and clinical outcomes . RESULTS Of the 6,795 subjects assigned to clopidogrel , 4,794 ( 70.6 % ) were on a CYP3A4-metabolized statin , and 966 ( 14.2 % ) were on a CCB at r and omization . The risk of cardiovascular ( CV ) death , myocardial infa rct ion ( MI ) , or stroke was similar regardless of baseline use of statins ( adjusted hazard ratio [ HR ] : 1.02 , 95 % confidence interval [ CI ] : 0.85 to 1.22 ) or CCBs ( adjusted HR : 1.16 ; 95 % CI : 0.94 to 1.43 ) in clopidogrel-treated patients . Further , the combined use of a CCB and atorvastatin 80 mg daily ( adjusted HR : 0.82 ; 95 % CI : 0.37 to 1.84 ) , or a CCB , statin , and proton pump inhibitor ( adjusted HR : 1.04 ; 95 % CI : 0.70 to 1.54 ) were not associated with an increased risk of CV death , MI , or stroke . The use of statins or CCBs did not modify the relative efficacy of prasugrel versus clopidogrel for the primary endpoint ( p for interaction = 0.43 , 0.55 , respectively ) . CONCLUSIONS In patients with ACS undergoing PCI , the use of statins or CCBs was not associated with an increased risk of CV events in clopidogrel-treated patients . Consistent results were observed when the drugs were administered alone , together , or in combination with proton pump inhibitors BACKGROUND The mechanism underlying statin-induced event reduction in patients with acute coronary syndrome remains unclear . AIMS To assess the efficacy of rosuvastatin 20 mg versus atorvastatin 80 mg in reducing the apolipoprotein B/apolipoprotein A-1 ( apoB/apoA-1 ) ratio at 3 months . Non-inferiority of rosuvastatin 20 mg versus atorvastatin 80 mg in reducing low-density lipoprotein cholesterol at 1 and 3 months was also assessed . METHODS Patients with non-ST-elevation acute coronary syndrome were enrolled into this r and omized , double blind , parallel-group trial . RESULTS In total , 753 patients ( 369 , rosuvastatin 20 mg ; 384 , atorvastatin 80 mg ) were included in the intention-to-treat analysis ; 478 patients ( 226 , rosuvastatin 20 mg ; 252 , atorvastatin 80 mg ) were included in the per- protocol analysis . Rosuvastatin 20 mg was more effective than atorvastatin 80 mg in decreasing apoB/apoA-1 ratio at 1 month ( -44.4 % vs -42.9 % , p=0.02 ) but not at 3 months ( both -44.4 % , p=0.87 ) . Low-density lipoprotein cholesterol decreased by approximately 50 % after 1 and 3 months in both groups . Non-inferiority of rosuvastatin 20 mg versus atorvastatin 80 mg was demonstrated at 1 month ( difference , -0.3 % [ 95 % confidence interval , -2.7 ; + 2.1 ] ) , but not at 3 months ( + 1.0 % [ -1.6 ; 3.5 ] ) ( intention-to-treat analysis ) . In the per- protocol analysis , non-inferiority of rosuvastatin 20 mg was demonstrated at both 1 ( -0.7 % [ -3.5 ; 2.0 ] ) and 3 ( -0.5 % [ -3.5 ; 2.5 ] ) months . CONCLUSION In patients with non-ST-elevation acute coronary syndrome , rosuvastatin 20 mg decreased apoB/apoA-1 ratio at 1 month more than atorvastatin 80 mg . No difference could be shown at 3 months ; thus , the primary endpoint was not met OBJECTIVES The goal of this study was to investigate the impact of high-dose atorvastatin on the pharmacodynamic ( PD ) effects of double-dose clopidogrel in statin-naive patients with stable coronary artery disease ( CAD ) and high-on-treatment platelet reactivity ( HTPR ) while on st and ard-dose clopidogrel before percutaneous coronary intervention ( PCI ) . BACKGROUND Patients with HTPR are at increased risk of adverse cardiovascular events after PCI . High-dose statins improve prognosis in high-risk patients by lipid- and nonlipid-related mechanisms , including antithrombotic effects . METHODS The ACHIDO ( Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity ) study was a r and omized PD study of high-dose ( 80 mg ) atorvastatin in addition to double-dose ( 150 mg ) clopidogrel ( atorvastatin group , n = 38 ) versus double-dose clopidogrel alone ( control group , n = 38 ) in patients with HTPR . HTPR was defined as P2Y(12 ) reaction units ( PRU ) ≥235 by the VerifyNow P2Y12 assay . Platelet reactivity was evaluated immediately before PCI and at 10 and 30 days . RESULTS Patients r and omized to atorvastatin had lower PRU values ( 188 ± 48 vs. 223 ± 53 PRU , p < 0.01 ; primary endpoint ) and HTPR rates ( 16 % vs. 42 % , p < 0.01 ) at 30 days than patients in the control group . Statin treatment ( odds ratio [ OR ] : 3.8 , p = 0.011 ) , baseline PRU < 298 ( OR : 10.7 , p = 0.0001 ) , noncarrier status of CYP2C19 * 2 loss-of-function allele ( OR : 2.9 , p = 0.043 ) , and age ( OR : 0.94 , p = 0.032 ) were variables significantly associated with optimal PD response ( PRU < 235 ) at 30 days . No correlations were found between PRU and lipid fractions . CONCLUSIONS High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in our stable CAD patients with HTPR undergoing PCI  ( Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity [ ACHIDO ] ; NCT01335048 ) OBJECTIVE The objective of the present study was to observe the effects of different doses of rosuvastatin on cardiac protection in patients with acute coronary syndrome ( ACS ) after stent implantation . PATIENTS AND METHODS A total of 137 patients with ACS were selected from March 2014 to January 2015 and r and omly divided into : 1 . The conventional treatment group : 45 patients were treated with conventional drugs such as aspirin , clopidogrel , nitrates , and a β-blocker ; 2 . The conventional rosuvastatin dose group : 45 patients received 10 mg/d rosuvastatin before sleep in addition to routine therapy ; 3 . The large rosuvastatin dose group : 47 patients received 20 mg/d rosuvastatin before sleep in addition to routine therapy . The course of treatment was 12 weeks . At 1 , 6 , and 12 week , ultrasound echocardiography , electrocardiogram ( ECG ) , high-sensitivity C-reactive protein ( hs-CRP ) , and pro-brain natriuretic peptide ( pro-BNP ) levels were tested to evaluate the therapeutic effects . The ultrasonic imaging criteria included left ventricular end diastolic diameter ( LVEDD ) , left ventricular end systolic diameter ( LVESD ) , left ventricular end diastolic volume ( LVEDV ) , left ventricular end systolic volume ( LVESV ) , and left ventricular ejection fraction ( LVEF ) . RESULTS After 1 week , hs-CRP , pro-BNP , and echocardiography of the patients in the three groups showed no significant differences ( p>0.05 ) ; after 6 and 12 weeks , the levels of hs-CRP , M 
    Output:
    
Conclusions This meta- analysis confirmed that statins  reduce mortality in patients undergoing clopidogrel treatment without affecting platelet activation and aggregation