human
***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Intensive statin therapy can lower the risk of recurrence of major cardiac events in patients with acute coronary syndromes . This could be related to the ability of statins to increase levels of Endothelial Progenitor Cells ( EPCs ) , which were demonstrated to be favorably associated with a better prognosis and post-infa rct ion left ventricular remodeling in patients with ischemic heart disease . AIM OF THE STUDY First , to evaluate , in a r and omized clinical trial , the effect of an intensive vs a st and ard treatment with statins on EPC mobilization in patients undergoing a successful primary or rescue percutaneous coronary intervention ; secondary , to evaluate whether left ventricular remodeling could be influenced by statin therapy through EPC mobilization . METHODS Forty ST-segment elevation myocardial infa rct ion ( STEMI ) patients undergoing a successful primary or rescue PCI were r and omized to receive atorvastatin 80 mg immediately after the admission ( Intensive Treatment , IT ) or atorvastatin 20 mg from the day of the discharge ( St and ard Treatment , ST ) . CD34+/KDR+ EPC count by flow cytometry and left ventricular function by 2-D Echo were measured on admission , at discharge and at 4 months follow up . RESULTS We found that EPC count was similar in the two groups of patients both on admission and at discharge . At follow up , however , EPC count was higher in patients r and omized to IT compared to patients r and omized to ST ( 7.59+/-7.30 vs 3.04+/-3.93 , p=0.04 ) . However , LV volumes , ejection fraction and wall motion score index were similar in both groups . CONCLUSIONS An intensive statin treatment after primary or rescue PCI is associated with a higher EPC count at follow up as compared to st and ard treatment . This beneficial effect did not translate in an improvement of LV function CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data CONTEXT Percutaneous coronary intervention ( PCI ) is associated with excellent short-term improvements in ischemic symptoms , yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events ( MACE ) . OBJECTIVE To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI . DESIGN AND SETTING R and omized , double-blind , placebo-controlled trial conducted at 77 referral centers in Europe , Canada , and Brazil . PATIENTS A total of 1677 patients ( aged 18 - 80 years ) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL ( 3.5 - 7.0 mmol/L ) , with fasting triglyceride levels of less than 400 mg/dL ( 4.5 mmol/L ) . INTERVENTIONS Patients were r and omly assigned to receive treatment with fluvastatin , 80 mg/d ( n = 844 ) , or matching placebo ( n = 833 ) at hospital discharge for 3 to 4 years . MAIN OUTCOME MEASURE Survival time free of MACE , defined as cardiac death , nonfatal myocardial infa rct ion , or reintervention procedure , compared between the treatment and placebo groups . RESULTS Median time between PCI and first dose of study medication was 2.0 days , and median follow-up was 3.9 years . MACE-free survival time was significantly longer in the fluvastatin group ( P = .01 ) . One hundred eighty-one ( 21.4 % ) of 844 patients in the fluvastatin group and 222 ( 26.7 % ) of 833 patients in the placebo group had at least 1 MACE ( relative risk [ RR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.64 - 0.95 ; P = .01 ) . This result was independent of baseline total cholesterol levels ( above [ RR , 0.76 ; 95 % CI , 0.56 - 1.04 ] vs below [ RR , 0.77 ; 95 % CI , 0.57 - 1.02 ] the median ) . In subgroup analysis , the risk of MACE was reduced in patients with diabetes ( n = 202 ; RR , 0.53 ; 95 % CI , 0.29 - 0.97 ; P = .04 ) and in those with multivessel disease ( n = 614 ; RR , 0.66 ; 95 % CI , 0.48 - 0.91 ; P = .01 ) who received fluvastatin compared with those who received placebo . There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group . CONCLUSION Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events 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 Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality .  Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials Effects of atorvastatin on  early recurrent ischemic events in acute coronary syndromes . The MIRACL study : A r and omized controlled trial 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 ) The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris ( UAP ) or non-Q-wave myocardial infa rct ion ( NQMI ) can influence the serum level of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and interleukin-8 ( IL-8 ) 24 h later . Forty-four patients with rest chest pain and subendocardial ischem 
    Output:
    
agent
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
***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Intensive statin therapy can lower the risk of recurrence of major cardiac events in patients with acute coronary syndromes . This could be related to the ability of statins to increase levels of Endothelial Progenitor Cells ( EPCs ) , which were demonstrated to be favorably associated with a better prognosis and post-infa rct ion left ventricular remodeling in patients with ischemic heart disease . AIM OF THE STUDY First , to evaluate , in a r and omized clinical trial , the effect of an intensive vs a st and ard treatment with statins on EPC mobilization in patients undergoing a successful primary or rescue percutaneous coronary intervention ; secondary , to evaluate whether left ventricular remodeling could be influenced by statin therapy through EPC mobilization . METHODS Forty ST-segment elevation myocardial infa rct ion ( STEMI ) patients undergoing a successful primary or rescue PCI were r and omized to receive atorvastatin 80 mg immediately after the admission ( Intensive Treatment , IT ) or atorvastatin 20 mg from the day of the discharge ( St and ard Treatment , ST ) . CD34+/KDR+ EPC count by flow cytometry and left ventricular function by 2-D Echo were measured on admission , at discharge and at 4 months follow up . RESULTS We found that EPC count was similar in the two groups of patients both on admission and at discharge . At follow up , however , EPC count was higher in patients r and omized to IT compared to patients r and omized to ST ( 7.59+/-7.30 vs 3.04+/-3.93 , p=0.04 ) . However , LV volumes , ejection fraction and wall motion score index were similar in both groups . CONCLUSIONS An intensive statin treatment after primary or rescue PCI is associated with a higher EPC count at follow up as compared to st and ard treatment . This beneficial effect did not translate in an improvement of LV function CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data CONTEXT Percutaneous coronary intervention ( PCI ) is associated with excellent short-term improvements in ischemic symptoms , yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events ( MACE ) . OBJECTIVE To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI . DESIGN AND SETTING R and omized , double-blind , placebo-controlled trial conducted at 77 referral centers in Europe , Canada , and Brazil . PATIENTS A total of 1677 patients ( aged 18 - 80 years ) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL ( 3.5 - 7.0 mmol/L ) , with fasting triglyceride levels of less than 400 mg/dL ( 4.5 mmol/L ) . INTERVENTIONS Patients were r and omly assigned to receive treatment with fluvastatin , 80 mg/d ( n = 844 ) , or matching placebo ( n = 833 ) at hospital discharge for 3 to 4 years . MAIN OUTCOME MEASURE Survival time free of MACE , defined as cardiac death , nonfatal myocardial infa rct ion , or reintervention procedure , compared between the treatment and placebo groups . RESULTS Median time between PCI and first dose of study medication was 2.0 days , and median follow-up was 3.9 years . MACE-free survival time was significantly longer in the fluvastatin group ( P = .01 ) . One hundred eighty-one ( 21.4 % ) of 844 patients in the fluvastatin group and 222 ( 26.7 % ) of 833 patients in the placebo group had at least 1 MACE ( relative risk [ RR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.64 - 0.95 ; P = .01 ) . This result was independent of baseline total cholesterol levels ( above [ RR , 0.76 ; 95 % CI , 0.56 - 1.04 ] vs below [ RR , 0.77 ; 95 % CI , 0.57 - 1.02 ] the median ) . In subgroup analysis , the risk of MACE was reduced in patients with diabetes ( n = 202 ; RR , 0.53 ; 95 % CI , 0.29 - 0.97 ; P = .04 ) and in those with multivessel disease ( n = 614 ; RR , 0.66 ; 95 % CI , 0.48 - 0.91 ; P = .01 ) who received fluvastatin compared with those who received placebo . There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group . CONCLUSION Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events 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 Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality .  Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials Effects of atorvastatin on  early recurrent ischemic events in acute coronary syndromes . The MIRACL study : A r and omized controlled trial 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 ) The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris ( UAP ) or non-Q-wave myocardial infa rct ion ( NQMI ) can influence the serum level of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and interleukin-8 ( IL-8 ) 24 h later . Forty-four patients with rest chest pain and subendocardial ischem 
    Output:
    