***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 The use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practice d despite lack of proven benefit . We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and /or severity of acute gout flares . METHODS Patients starting allopurinol for crystal-proven chronic gouty arthritis were r and omized to receive colchicine 0.6 mg po bid or placebo in a r and omized , prospect i ve , double blind , placebo controlled trial . Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl . Treatment arms were analyzed regarding frequency of flares , likelihood of any flare or multiple flares , severity of flares on the visual analog scale ( VAS ) , and length of flares in days . RESULTS Forty-three subjects were studied . Subjects treated with colchicine experienced fewer total flares ( 0.52 vs 2.91 , p = 0.008 ) , fewer flares from 0 to 3 months ( 0.57 vs 1.91 , p = 0.022 ) , fewer flares 3 - 6 months ( 0 vs 1.05 , p = 0.033 ) , less severe flares as reported on VAS ( 3.64 vs 5.08 , p = 0.018 ) , and fewer recurrent gout flares ( p = 0.001 ) . Colchicine was well tolerated . CONCLUSION Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares , and reduces the likelihood of recurrent flares . Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data Background — Although gout and hyperuricemia are related to several conditions that are associated with reduced survival , no prospect i ve data are available on the independent impact of gout on mortality . Furthermore , although many studies have suggested that hyperuricemia is associated with cardiovascular disease ( CVD ) , limited data are available on the impact of gout on CVD . Methods and Results — Over a 12-year period , we prospect ively examined the relation between a history of gout  and the risk of death and myocardial infa rct ion in 51 297 male participants of the Health Professionals Follow-Up Study . During the 12 years of follow-up , we documented 5825 deaths from all causes , which included 2132 deaths from CVD and 1576 deaths from coronary heart disease ( CHD ) . Compared with men without history of gout and CHD at baseline , the multivariate relative risks among men with history of gout were 1.28 ( 95 % confidence interval [ CI ] , 1.15 to 1.41 ) for total mortality , 1.38 ( 95 % CI , 1.15 to 1.66 ) for CVD deaths , and 1.55 ( 95 % CI , 1.24 to 1.93 ) for fatal CHD . The corresponding relative risks among men with preexisting CHD were 1.25 ( 95 % CI , 1.09 to 1.45 ) , 1.26 ( 95 % CI , 1.07 to 1.50 ) , and 1.24 ( 95 % CI , 1.04 to 1.49 ) , respectively . In addition , men with gout had a higher risk of nonfatal myocardial infa rct ion than men without gout ( multivariate relative risk , 1.59 ; 95 % CI , 1.04 to 2.41 ) . Conclusions — These prospect i ve data indicate that men with gout have a higher risk of death from all causes . Among men without preexisting CHD , the increased mortality risk is primarily a result of an elevated risk of CVD death , particularly from CHD Objectives : To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout , and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment . Methods : Prospect i ve , multicentre , open-label , two-stage r and omised controlled trial in gout patients with normal renal function . Enrolled patients were given 300 mg allopurinol for 2 months ( stage 1 ) . Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration ( sUr ) ⩽0.30 mmol/l ( 5.0 mg/dl ) , which was defined as successful , were r and omised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months ( stage 2 ) . Results : 96 patients were enrolled in stage 1 . 82 patients ( 85 % ) were eligible for the analysis at the end of stage 1 : there was a mean ( SD ) decrease in sUr concentration of 35 (11)% from baseline ; 20 patients ( 24 % ) attained target sUr ⩽0.30 mmol/l ; and 9 patients ( 11 % ) stopped allopurinol because of adverse drug reactions . 62 patients were enrolled in stage 2 . 27 patients received benzbromarone ( 3 patients not eligible for analysis ) and 35 received probenecid ( 4 patients not eligible for analysis ) . Treatment with benzbromarone was successful in 22/24 patients ( 92 % ) and with probenecid in 20/31 patients ( 65 % ) ( p = 0.03 compared with benzbromarone ) . Compared with baseline values , there was a mean ( SD ) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid ( p<0.001 ) . Conclusion : This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr ⩽0.30 mmol/l , following 2 months of treatment . In stage 2 , benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day . Trial registration number : IS RCT N21473387 Aim Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents . Methods Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [ baseline serum urate levels ( sUA ) ≥8.0 mg/dl ] enrolled in a 6-month r and omized controlled trial comparing  urate-lowering efficacy ( ULE ) and safety of daily xanthine oxidase inhibitors ( XOIs ) febuxostat ( 40 mg or 80 mg ) and allopurinol ( 200 mg or 300 mg ) . We compared baseline demographic , gout and co-morbid characteristics , ULE , and safety  of XOI treatment in diabetic and non-diabetic gout patients .  ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl . Safety was monitored throughout the trial . Results Diabetic gout patients were older , more frequently female , and had longer gout duration . Co-morbidities were more frequent among diabetic patients : cardiovascular disease ; impaired renal function ; hyperlipidemia ; and obesity ( body mass index > 30 kg/m2 ) ( p < 0.001 for all comparisons ) . Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol ( p < 0.050 ) at all levels of renal function , achieving sUA goal range in the majority of diabetic and non-diabetic patients . Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events . Conclusions Despite higher co-morbidity rates in diabetic patients , febuxostat and allopurinol were safe in both groups at the doses tested . Febuxostat 80 mg achieved sUA < 6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses Introduction The purpose of this study was to compare urate-lowering ( UL ) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate ( sUA ) ≥ 8.0 mg/dL in a six-month trial . Methods Subjects ( n = 2,269 ) were r and omized to febuxostat 40 mg or 80 mg , or allopurinol 300 mg ( 200 mg in moderate renal impairment ) . Endpoints included the proportion of all subjects with sUA < 6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA < 6.0 mg/dL. Safety assessment s included blinded adjudication of each cardiovascular ( CV ) adverse event ( AE ) and death . Results Comorbidities included : renal impairment ( 65 % ) ; obesity ( 64 % ) ; hyperlipidemia ( 42 % ) ; and hypertension ( 53 % ) . In febuxostat 40 mg , febuxostat 80 mg , and allopurinol groups , primary endpoint was achieved in 45 % , 67 % , and 42 % , respectively . Febuxostat 40 mg UL was statistically non-inferior to allopurinol , but febuxostat 80 mg was superior to both ( P < 0.001 ) . Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg ( 72 % ; P < 0.001 ) compared with febuxostat 40 mg ( 50 % ) or allopurinol ( 42 % ) , but febuxostat 40 mg showed greater efficacy than allopurinol ( P = 0.021 ) . Rates of AEs did not differ across treatment groups . Adjudicated ( APTC ) CV event rates were 0.0 % for febuxostat 40 mg and 0.4 % for both febuxostat 80 mg and allopurinol . One death occurred in each febuxostat group and three in the allopurinol group . Conclusions Urate-lowering efficacy  of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol ( 300/200 mg ) , which were comparable . In subjects with mild/moderate renal impairment , both febuxostat doses were more efficacious than allopurinol and equally safe . At the doses tested , safety of febuxostat and allopurinol was comparable . Clinical Trial Registration Introduction Gout affects 2.5 % of the UK 's adult population and is now the most common type of inflammatory arthritis . The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors , such as allopurinol . Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008 . The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol , which has been named the Febuxostat versus Allopurinol Streamlined trial ( FAST ) . Methods and analysis FAST is a cardiovascular safety study using the prospect i ve , r and omised , open , blinded endpoint design . FAST is recruiting in the UK and Denmark . Recruited patients are aged over 60 years , prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor . After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism ( EULAR ) urate targets ( serum urate < 357 µmol/L ) , patients are r and omised to either continue optimal dose allopurinol or to use febuxostat . Patients are followed-up for an average of 3 years . The primary endpoint is first occurrence of the Anti-Platelet Trialists ’ Collaboration ( APTC ) cardiovascular endpoint of non-fatal myocardial infa rct ion , non-fatal stroke or cardiovascular death . Secondary endpoints are all cause mortality and hospitalisations for heart failure , unstable , new or worsening angina , coronary or cerebral revascularisation , transient ischaemic attack , non-fatal cardiac arrest , venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia . The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3 . Ethics and dissemination FAST ( IS RCT N72443728 ) has ethical approval in the UK and Denmark , and results will be published in a peer review ed journal . Trial Registration number FAST is registered in the EU Clinical Trials Register ( EUDRACT No : 201 
    Output:
    
CV events did not decrease over time .
Comparing shorter studies ( < 52 weeks ) to longer ones did not reveal any statistical differences .
However , in long-term studies with febuxostat vs allopurinol , results were nearly significant , with more CVE occurring with febuxostat treatment .
Conclusion RCT data do not suggest differences in CV events among ULTs in gout .
Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid