***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 —The use of a stent to deliver a drug may reduce in-stent restenosis .  Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules , thereby arresting mitosis . Methods and Results —On the basis of prior animal studies , the European evaLUation of the pacliTaxel Eluting Stent ( ELUTES ) pilot clinical trial ( n=190 ) investigated the safety and efficacy of V-Flex Plus coronary stents ( Cook Inc ) coated with escalating doses of paclitaxel ( 0.2 , 0.7 , 1.4 , and 2.7 & mgr;g/mm2 stent surface area ) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone . The primary efficacy end point was angiographic percent diameter stenosis at 6 months . At angiographic follow-up , percent diameter stenosis was 33.9±26.7 % in controls ( n=34 ) and 14.2±16.6 % in the 2.7-&mgr;g/mm2 group ( n=31 ; P = 0.006 ) . Late loss decreased from 0.73±0.73 to 0.11±0.50 mm ( P = 0.002 ) . Binary restenosis ( ≥50 % at follow-up ) decreased from 20.6 % to 3.2 % ( P = 0.056 ) , with no significant benefit from intermediate paclitaxel doses . Freedom from major adverse cardiac events in the highest ( effective ) dose group was 92 % , 89 % , and 86 % at 1 , 6 , and 12 months , respectively ( P = NS versus control ) . No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only . Conclusions —Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent , at a dose density of 2.7 & mgr;g/mm2 , reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects Background —The safety and efficacy of sirolimus-eluting stenting have been demonstrated , but the outcome of patients treated with this novel technology beyond the first year remains unknown . We sought to evaluate the angiographic , intravascular ultrasound ( IVUS ) , and clinical outcomes of patients treated with sirolimus-eluting stents 2 years after implantation . Methods and Results —This study included 30 patients treated with sirolimus-eluting Bx Velocity stenting ( slow release [ SR ] , n=15 , and fast release [ FR ] , n=15 ) in São Paulo , Brazil . Twenty-eight patients underwent 2-year angiographic and IVUS follow-up .  No deaths occurred during the study period . In-stent late loss was slightly greater in the FR group ( 0.28±0.4 mm ) than in the SR group ( −0.09±0.23 mm , P = 0.007 ) . No patient had in-stent restenosis . At 2-year follow-up , only 1 patient ( FR group ) had a 52 % diameter stenosis within the lesion segment , which required repeat revascularization . The target-vessel revascularization rate for the entire cohort was 10 % ( 3/30 ) at 2 years . All other patients had ≤35 % diameter stenosis . Angiographic lumen loss at the stent edges was also minimal ( in-lesion late loss was 0.33±0.42 mm [ FR ] and 0.13±0.29 mm [ SR ] ) . In-stent neointimal hyperplasia volume , as detected by IVUS , remained minimal after 2 years ( FR= 9.90±9 mm3 and SR=10.35±9.3 mm3 ) . Conclusions —This study demonstrates the safety and efficacy of sirolimus-eluting Bx Velocity stents 2 years after implantation in humans . In-stent lumen dimensions remained essentially unchanged at 2-year follow-up in the 2 groups , although angiographic lumen loss was slightly higher in the FR group . Restenosis “ catch-up ” was not found in our patient population 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 BACKGROUND The placement of stents in coronary arteries has been shown to reduce restenosis in comparison to balloon angioplasty . However , clinical use of intracoronary stents is impeded by the risk of subacute stent thrombosis and complications associated with the anticoagulant regimen . To reduce these complications , the hypothesis that systemic anticoagulation is not necessary when adequate stent expansion is achieved was prospect ively evaluated on a consecutive series of patients who received intracoronary stents .  METHODS AND RESULTS From March 1993 to January 1994 , 359 patients underwent Palmaz-Schatz coronary stent insertion .  After an initial successful angiographic result with < 20 % stenosis by visual estimation had been achieved , intravascular ultrasound imaging was performed . Further balloon dilatation of the stent was guided by observation of the intravascular ultrasound images . All patients with adequate stent expansion confirmed by ultrasound were treated only with antiplatelet therapy ( either ticlopidine for 1 month with short-term aspirin for 5 days or only aspirin ) after the procedure . Clinical success ( procedure success without early postprocedural events ) at 2 months was achieved in 338 patients ( 94 % ) . With an inflation pressure of 14.9 + /- 3.0 atm and a balloon-to-vessel ratio of 1.17 + /- 0.19 , optimal stent expansion was achieved in 321 of the 334 patients ( 96 % ) who underwent intravascular ultrasound evaluation , with these patients receiving only antiplatelet therapy after the procedure . Despite the absence of anticoagulation , there were only two acute stent thromboses ( 0.6 % ) and one subacute stent thrombosis ( 0.3 % ) at 2-month clinical follow-up . Follow-up angiography at 3 to 6 months documented two additional occlusions ( 0.6 % ) at the stent site . At 6-month clinical follow-up , angiographically documented stent occlusion had occurred in 5 patients ( 1.6 % ) . At 6-month clinical follow-up , there was a 5.7 % incidence of myocardial infa rct ion , a 6.4 % rate of coronary bypass surgery , and a 1.9 % incidence of death . Emergency intervention ( emergency angioplasty or bailout stent ) for a stent thrombosis event was performed in 3 patients ( 0.8 % ) . The overall event rate was relatively high because of intraprocedural complications that occurred in 16 patients ( 4.5 % ) . Intraprocedural complications , however , decreased to 1 % when angiographically appropriately sized balloons were used for final stent dilations . There was one ischemic vascular complication that occurred at the time of the procedure and one ischemic vascular complication that occurred at the time of angiographic follow-up . By 6 months , repeat angioplasty for symptomatic restenosis was performed in 47 patients ( 13.1 % ) . CONCLUSIONS The Palmaz-Schatz stent can be safely inserted in coronary arteries without subsequent anticoagulation provided that stent expansion is adequate and there are no other flow-limiting lesions present . The use of high-pressure final balloon dilatations and confirmation of adequate stent expansion by intravascular ultrasound provide assurance that anticoagulation therapy can be safely omitted . This technique significantly reduces hospital time and vascular complications and has a low stent thrombosis rate Background —We have previously reported the safety and effectiveness of sirolimus-eluting stents for the treatment of de novo coronary lesions . The present investigation explored the potential of this technology to treat in-stent restenosis . Methods and Results —Twenty-five patients with in-stent restenosis were successfully treated with the implantation of 1 or 2 sirolimus-eluting Bx VELOCITY stents in São Paulo , Brazil . Nine patients received 2 stents ( 1.4 stents per lesion ) . Angiographic and volumetric intravascular ultrasound ( IVUS ) images were obtained after the procedure and at 4 and 12 months . All vessels were patent at the time of 12-month angiography . Angiographic late loss averaged 0.07±0.2 mm in-stent and −0.05±0.3 mm in-lesion at 4 months , and 0.36±0.46 mm in-stent and 0.16±0.42 mm in-lesion after 12 months . No patient had in-stent or stent margin restenosis at 4 months , and only one patient developed in-stent restenosis at 1-year follow-up . Intimal hyperplasia by 3-dimensional IVUS was 0.92±1.9 mm3 at 4 months and 2.55±4.9 mm3 after 1 year . Percent volume obstruction was 0.81±1.7 % and 1.76±3.4 % at the 4- and 12-month follow-up , respectively . There was no evidence of stent malapposition either acutely or in the follow-up IVUS images , and there were no deaths , stent thromboses , or repeat revascularizations . Conclusion —This study demonstrates the safety and the potential utility of sirolimus-eluting Bx VELOCITY stents for the treatment of in-stent restenosis Background —We have previously reported a virtual absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting stents . The aim of the present investigation was to determine whether these results are sustained over a period of 1 year . Methods and Results —Forty-five patients with de novo coronary disease were successfully treated with the implantation of a single sirolimus-eluting Bx VELOCITY stent in São Paulo , Brazil ( n=30 , 15 fast release [ group I , GI ] and 15 slow release [ GII ] ) and Rotterdam , The Netherl and s ( 15 slow release , GIII ) . Angiographic and volumetric intravascular ultrasound ( IVUS ) follow-up was obtained at 4 and 12 months ( GI and GII ) and 6 months ( GIII ) . In-stent minimal lumen diameter and percent diameter stenosis remained essentially unchanged in all groups ( at 12 months , GI and GII ; at 6 months , GIII ) . Follow-up in-lesion minimal lumen diameter was 2.28 mm ( GIII ) , 2.32 mm ( GI ) , and 2.48 mm ( GII ) . No patient approached the ≥50 % diameter stenosis at 1 year by angiography or IVUS assessment , and no edge restenosis was observed . Neointimal hyperplasia , as detected by IVUS , was virtually absent at 6 months ( 2±5 % obstruction volume , GIII ) and at 12 months ( GI=2±5 % and GII=2±3 % ) . Conclusions —This study demonstrates a sustained suppression of neointimal proliferation by sirolimus-eluting Bx VELOCITY stents 1 year after implantation Background —Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient population s. Methods and Results —We conducted a r and omized , double-blind trial of 536 patients at 38 medical centers evaluating slow-release ( SR ) and moderate-release ( MR ) formulations of a polymer-based paclitaxel-eluting stent ( TAXUS ) for revascularization of single , primary lesions in native coronary arteries . Cohort I compared TAXUS-SR with control stents , and Cohort II compared TAXUS-MR with a second control group . The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound . Secondary end points were 6-month angiographic restenosis and 6- and 12-month inc 
    Output:
    
At 12-month follow-up , sirolimus- or paclitaxel-eluting stents were effective and safe in patients with de novo lesions and low or medium risk of restenosis .
At current market prices , the widespread use of these stents would involve an increase in health care expenditure for the different sensitivity scenarios we evaluated .