***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: Objective Secondary prevention in patients with critical limb ischemia ( CLI ) is crucial for the reduction of cardiovascular morbidity and mortality . Nonetheless , current recommendations are extrapolated from other high‐risk population s because of the lack of CLI‐dedicated trials . The aim of this explorative study was to evaluate the association of statin therapy with the outcomes of CLI patients . Methods The First‐Line  Treatments in Patients With Critical Limb Ischemia ( CRITISCH ) registry is a prospect i ve multicenter registry analyzing the effectiveness of all available treatment strategies in 1200 CLI patients . For the purpose s of this analysis , patients were divided into two groups based on statin administration . Treatment crossovers and nonadherent patients were excluded from analysis . The primary composite end point of this study was the amputation‐free survival ( AFS ) . Major adverse cardiovascular and cerebral events ( MACCEs ) , time to death , and time to major amputation were also analyzed . Results Statin therapy was applied in 445 individuals ( 37 % ) , 371 ( 31 % ) patients received no statins , and 384 subjects were excluded from analysis ( treatment crossovers ) . Patients receiving statins were more likely to be younger ( P < .001 ) and to have a history of coronary heart disease ( P < .001 ) or previous intervention at index limb ( P < .001 ) . Patients receiving statin therapy had a lower hazard regarding AFS ( hazard ratio [ HR ] , 0.45 ; 95 % confidence interval [ CI ] , 0.34‐0.63 ; P < .001 ) and death ( HR , 0.40 ; 95 % CI , 0.24‐0.66 ; P < .001 ) as well as lower odds of MACCE ( odds ratio , 0.41 ; 95 % CI , 0.23‐0.69 ; P = .001 ) . However , statin therapy was not associated with reduced amputation rates ( HR , 1.02 ; 95 % CI , 0.67‐1.56 ; P = .922 ) . Statin effect on AFS was consistent among diabetics ( HR , 0.47 ; 95 % CI , 0.31‐0.70 ; P < .001 ) , patients with chronic kidney disease ( HR , 0.53 ; 95 % CI , 0.32‐0.87 ; P = .012 ) , and patients older than 75 years ( HR , 0.40 ; 95 % CI , 0.26‐0.60 ; P < .001 ) . Statin administration was also associated with an improved AFS in patients with antiplatelet medication ( HR , 0.64 ; 95 % CI , 0.41‐0.99 ; P = .049 ) and without antiplatelet medication ( HR , 0.26 ; 95 % CI , 0.12‐0.57 ; P = .001 ) and after both endovascular therapy ( HR , 0.51 ; 95 % CI , 0.34‐0.76 ; P = .001 ) and bypass revascularization ( HR , 0.38 ; 95 % CI , 0.21‐0.68 ; P = .001 ) . Conclusions Statin therapy in CLI patients is associated with an increased AFS and lower rates of mortality and MACCEs without improving , however , the salvage rates of the affected limb In patients with peripheral artery disease ( PAD ) , statins may improve the symptoms of claudication . The Intermittent Claudication Proof of Principle ( ICPOP ) study tested the hypothesis that the combination of extended release niacin plus lovastatin would improve exercise performance in patients with PAD and claudication compared with a diet intervention . A phase 3 double-blind , parallel-group , multi-center , 28-week multi-national study evaluated subjects with a history of claudication who had an ankle — brachial index ( ABI ) ≤ 0.90 , a reproducible peak treadmill walking time ( PWT ) of 1—20 minutes , and a low-density lipoprotein (LDL)-cholesterol level < 160 mg/dl ( < 4.1 mmol/l ) . Subjects were r and omly assigned to low-dose niacin 1000 mg plus lovastatin 40 mg ( low niacin — statin ) , high-dose niacin 2000 mg plus lovastatin 40 mg ( high niacin — statin ) , or diet intervention ( diet ) . The co- primary efficacy endpoint of percent change in PWT and claudication onset time ( COT ) at 28 weeks was assessed using a grade d treadmill protocol . At completion , 385 subjects were analyzed for safety and 370 subjects were analyzed for efficacy . The primary efficacy analysis showed no statistical significance for overall treatment effect at week 28 for the co- primary endpoint of PWT and COT . The PWT component of the primary endpoint increased 26.5 % on diet , 37.8 % on high niacin — statin ( p = 0.137 ) and 38.6 % on low niacin — statin ( p = 0.096 ) . Flushing as the most common event leading to discontinuation and treatment was associated with increases in liver enzymes , fasting blood glucose concentration and a decrease in platelet count OBJECTIVE A population -based point-prevalence study was conducted to determine the prevalence of peripheral arterial disease ( PAD ) in Sweden , with special attention to critical limb ischemia and sex differences . METHODS An age-st and ardized r and omly selected population sample of 8000 women and men , aged 60 to 90 years , from four different regions in Sweden was invited to participate . The sample had the same age and gender distribution as the Swedish population in this age group . Participating subjects completed question naires on medical history , present medication , and symptoms , and their ankle-brachial index ( ABI ) was measured . Subjects were analyzed for presence of PAD according to reported symptoms and an ABI<0.9 . RESULTS A total of 5080 subjects were included , giving a participation rate of 64 % . The prevalence of any PAD , asymptomatic PAD , intermittent claudication , and severe limb ischemia was , respectively , 18 % ( 95 % confidence interval [ CI ] , 16 % to 20 % ) 11 % ( 9 % to 13 % ) , 7 % ( 6.5 to 7 % ) and 1.2 % ( 1 % to 1.5 % ) . Women had a higher prevalence than men when PAD was diagnosed with ABI only ; that is , asymptomatic PAD ( 12.6 % vs 9.4 % , P=.03 ) and severe limb ischemia ( 1.5 % vs 0.8 % , P<.008 ) . The prevalence of any PAD was 7.9 % in the age group 60 to 65 years and increased to 47.2 % among the age group 85 to 90 years . Severe limb ischemia occurred in 0.3 % in the youngest age group , was highest in the age group 80 to 84 years at 3.3 % , and declined to 2.5 % among the oldest . The prevalence of PAD differed between regions ( P<.0001 ) . CONCLUSIONS PAD is common in Sweden , and almost a fifth of all elderly individuals have some stage of this disease . Women are more often afflicted than men . The prevalence of severe ischemia , as a measure of critical limb ischemia , is about 1 % the population Background —Cholesterol modification reduces cardiovascular events in patients with atherosclerosis , including those with peripheral arterial disease . The purpose of this study was to determine whether cholesterol lowering with atorvastatin improves walking performance in patients with intermittent claudication . Methods and Results —This r and omized , double-blind , parallel- design study included 354 persons with claudication attributable to peripheral arterial disease . Patients were treated with placebo , atorvastatin ( 10 mg per day ) , or atorvastatin ( 80 mg per day ) for 12 months . The outcome measures included change in treadmill exercise time and patient-reported measures of physical activity and quality of life based on question naires . Maximal walking time after 12 months of treatment with atorvastatin did not change significantly . However , there was improvement in pain-free walking time after 12 months of treatment for the 80-mg ( P = 0.025 ) group compared with placebo . A physical activity question naire demonstrated improvement in ambulatory ability for the 10- and 80-mg groups ( P = 0.011 ) , whereas 2 quality of life instruments , the Walking Impairment Question naire and Short Form 36 Question naire , did not show significant change . Conclusions —Atorvastatin improves pain-free walking distance and community-based physical activity in patients with intermittent claudication . When treated with atorvastatin , patients with peripheral arterial disease may experience improvement in symptoms to complement the anticipated reduction in cardiovascular events reported in other studies of statins Background : The PCSK9 ( proprotein convertase subtilisin/kexin type 9 ) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial ( Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk ) . We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease ( PAD ) as well as the effect on major adverse limb events . Methods : FOURIER was a r and omized trial of evolocumab versus placebo  in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years . Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of < 0.85 , or if they had a prior peripheral vascular procedure . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , stroke , hospital admission for unstable angina , or coronary revascularization . The key secondary end point was a composite of cardiovascular death , myocardial infa rct ion , or stroke . An additional outcome of interest was major adverse limb events defined as acute limb ischemia , major amputation , or urgent peripheral revascularization for ischemia . Results : Three thous and six hundred forty-two patients ( 13.2 % ) had PAD ( 1505 with no prior myocardial infa rct ion or stroke ) . Evolocumab significantly reduced the primary end point consistently in patients with PAD ( hazard ratio [ HR ] 0.79 ; 95 % confidence interval [ CI ] , 0.66–0.94 ; P=0.0098 ) and without PAD ( HR 0.86 ; 95 % CI , 0.80–0.93 ; P=0.0003 ; Pinteraction=0.40 ) . For the key secondary end point , the HRs were 0.73 ( 0.59–0.91 ; P=0.0040 ) for those with PAD and 0.81 ( 0.73–0.90 ; P<0.0001 ) for those without PAD ( Pinteraction=0.41 ) . Because of their higher risk , patients with PAD had larger absolute risk reductions for the primary end point ( 3.5 % with PAD , 1.6 % without PAD ) and the key secondary end point ( 3.5 % with PAD , 1.4 % without PAD ) . Evolocumab reduced the risk of major adverse limb events in all patients ( HR , 0.58 ; 95 % CI , 0.38–0.88 ; P=0.0093 ) with consistent effects in those with and without known PAD . There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events ( P=0.026 for the beta coefficient ) that extended down to < 10 mg/dL. Conclusions : Patients with PAD are at high risk of cardiovascular events , and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions . Moreover , lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01764633 Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies OBJECTIVES The Heart Protection Study ( HPS ) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events ( defined as myocardial infa rct ion , coronary death , stroke , or revascularization ) in patients with peripheral arterial disease ( PAD ) . In addition , the 
    Output:
    
Statin therapy was also associated with increased overall patency rates and lower incidence of MACCE .
In conclusion , statins are associated with decreased risk for amputation , mortality , and MACCE , as well as increased overall patency rates among patients with CLI .