***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 — A Department of Veterans Affairs Cooperative Study r and omized high-risk patients with medically refractory myocardial ischemia , a group largely excluded from previous trials , to urgent revascularization with either  percutaneous coronary intervention ( PCI ) or coronary artery bypass grafting ( CABG ) . The present study examined the cost-effectiveness of PCI versus CABG for these high-risk patients . Methods and Results — Of 454 patients at 16 Department of Veterans Affairs medical centers , 445 were available for the economic analysis ( 218 PCI and 227 CABG patients ) .  Total costs were assessed at 3 and 5 years from the third-party payer ’s perspective , and effectiveness was measured by survival . After 3 years , average total costs were $ 63 896 for PCI versus $ 84 364 for CABG patients , a difference of $ 20 468 ( 95 % confidence interval [ CI ] $ 13 918 to $ 27 569 ) . CIs were estimated by bootstrapping . Survival at 3 years was 0.82 for PCI versus 0.79 for CABG patients ( P=0.34 ) . Precision of the cost-effectiveness estimates were assessed by bootstrapping . PCI was less costly and more effective at 3 years in 92.6 % of the bootstrap replications . After 5 years , average total costs were $ 81 790 for PCI versus $ 100 522 for CABG patients , a difference of $ 18 732 ( 95 % CI $ 9873 to $ 27 831 ) , whereas survival at 5 years was 0.75 for PCI patients versus 0.70 for CABG patients ( P=0.21 ) . At 5 years , PCI remained less costly and more effective in 89.4 % of the bootstrap replications . Conclusions — PCI was less costly and at least as effective for the urgent revascularization of medically refractory , high-risk patients over 5 years BACKGROUND The Valsartan Heart Failure Trial ( Val-HeFT ) compared valsartan versus placebo in 5010 patients taking prescribed background therapy for New York Heart Association class II to IV heart failure .  Valsartan reduced the risk of heart failure hospitalization and improved clinical signs and symptoms of heart failure . We sought to compare re source use , costs , and health outcomes among patients taking prescribed therapy for heart failure and r and omly assigned to receive valsartan or placebo .  METHODS Measures of re source use were based on data collected during the trial . Unit cost estimates were collected from individual countries and converted to 1999 US dollars . Total costs were estimated for hospitalizations , inpatient and outpatient physician services , ambulance transportation , deaths outside the hospital , and outpatient cardiovascular medications . RESULTS Mean follow-up was 23 months . Mean costs for heart failure hospitalizations were 423 dollars lower among patients receiving valsartan ( 95 % CI , -706 to -146 ) . Mean total costs were 9008 dollars for patients receiving valsartan and 8464 dollars for patients receiving placebo , a net incremental cost of 545 dollars ( 95 % CI , -149 to 1148 ) , including the cost of valsartan . There was an overall reduction in total costs of 929 dollars ( 95 % CI , -3243 to 1533 ) among patients not receiving an ACE inhibitor at baseline but a slight increase in costs of 334 dollars ( 95 % CI , -497 to 1199 ) among those receiving an ACE inhibitor without a beta-blocker and a 1246 dollars increase ( 95 % CI , 54 to 2230 ) in patients receiving both an ACE inhibitor and a beta-blocker at baseline . CONCLUSIONS Valsartan provided clinical benefits at a mean incremental cost of 285 dollars per year during the trial . In patients not taking ACE inhibitors , valsartan was economically attractive , increasing survival while reducing or marginally increasing overall costs OBJECTIVE To determine the incremental cost-effectiveness of clopidogrel plus aspirin ( C + A ) compared with aspirin ( A ) alone during the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management and Avoidance ( CHARISMA ) trial from a US payer perspective . BACKGROUND Although the CHARISMA trial did not find a benefit of adding clopidogrel to aspirin in its overall study cohort , a benefit was suggested in a prespecified subgroup of patients with established cardiovascular ( CV ) disease . The cost-effectiveness of dual antiplatelet therapy in this population is unknown . METHODS Medical re source utilization was assessed prospect ively , and costs for hospitalizations , physician services , outpatient care , and medications were assigned using 2007 US dollars . Life expectancy was estimated contingent on fatal and nonfatal CV events using statistical models of long-term survival from the Saskatchewan Health data base . RESULTS C + A was associated with a 12.5 % relative reduction in CV death , myocardial infa rct ion , or stroke compared with A alone ( 6.9 % vs. 7.9 % , P = 0.048 ) over a median 28 months of follow-up . Severe or moderate bleeding events were higher in patients receiving C + A versus A alone ( 3.6 % vs. 2.5 % , P < 0.001 ) . Mean cost/patient was $ 2607 higher for C + A , while projected life expectancy increased by an average of 0.072 years due to fewer in-trial events . The result ing incremental cost-effectiveness ratio ( ICER ) for C + A was $ 36,343/year of life gained . Findings were insensitive to discount rate , life expectancy projections , post-event costs , and indirect costs from lost productivity ; the ICER was most sensitive to the cost of clopidogrel . Bootstrap analysis demonstrated that the ICER for C + A remained < $ 50,000/life-year gained in 70.6 % of bootstrap replicates and < $ 100,000/life-year gained in 87.4 % . CONCLUSIONS Among patients with established CV disease , adding clopidogrel to aspirin appears to increase life expectancy modestly at a cost generally considered acceptable within the US health-care system BACKGROUND Functional benefit in  heart failure due to idiopathic dilated cardiomyopathy has been observed after beta-blockade , but improvement in survival has not been established in a large-scale r and omized trial . This was the main objective of the Cardiac Insufficiency Bisoprolol Study ( CIBIS ) . METHODS AND RESULTS Six hundred forty-one patients with chronic heart failure of various etiologies and a left ventricular ejection fraction of < 40 % entered this placebo-controlled , r and omized , double-blind study . Patients were in New York Heart Association functional class III ( 95 % ) or IV ( 5 % ) at inclusion . All received background diuretic and vasodilator therapy ( an angiotensin-converting enzyme inhibitor in 90 % of cases ) . A total of 320 patients was r and omized to bisoprolol  and 321 to placebo .  Mean follow-up was 1.9 years . Bisoprolol was well tolerated without between group difference in premature treatment withdrawals ( 82 on placebo , 75 on bisoprolol ; NS ) . The observed difference in mortality between groups did not reach statistical significance : 67 patients died on placebo , 53 on bisoprolol ( P = .22 ; relative risk , 0.80 ; 95 % confidence interval , 0.56 to 1.15 ) . No significant difference was observed in sudden death rate ( 17 on placebo , 15 on bisoprolol ) or death related to documented ventricular tachycardia or fibrillation ( 7 on placebo , 4 on bisoprolol ) . Bisoprolol significantly improved the functional status of the patients ; fewer patients in the bisoprolol group required hospitalization for cardiac decompensation ( 90 on placebo versus 61 on bisoprolol , P < .01 ) , and more patients improved by at least one New York Heart Association functional class ( 48 on placebo versus 68 on bisoprolol , P = .04 ) by the end of follow-up period . CONCLUSIONS These results confirm previous trials evidence that a progressively increasing dose of beta-blocker in severe heart failure confers functional benefit . Subgroup analysis suggested that benefit from beta-blockade therapy was greater for those with nonischemic cardiomyopathy . However , improvement in survival while on beta-blockade remains to be demonstrated OBJECTIVES To compare the clinical - and cost-effectiveness of minimally invasive direct coronary artery bypass grafting ( MIDCAB ) and percutaneous transluminal coronary angioplasty ( PTCA ) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery ( LAD ) . DESIGN Multi-centre r and omised trial without blinding . The computer-generated sequence of r and omised assignments was stratified by centre , allocated participants in blocks and was concealed using a central ised telephone facility . SETTING Four tertiary cardiothoracic surgery centres in Engl and . PARTICIPANTS Patients with ischaemic heart disease with at least 50 % proximal stenosis of the LAD , suitable for either PTCA or MIDCAB , and with no significant disease in another vessel . INTERVENTIONS Patients r and omised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure . Patients r and omised to MIDCAB had general anaesthetic . The chest was opened through an 8 - 10-cm left anterior thoracotomy . The ribs were retracted and the left internal thoracic artery ( LITA ) harvested . The pericardium was opened in the line of the LAD to confirm the feasibility of operation . The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD . All operators were experienced in carrying out MIDCAB . MAIN OUTCOME MEASURES The primary outcome measure was survival free from cardiac-related events . Relevant events were death , myocardial infa rct ion , repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up . Secondary outcome measures were complications , functional outcome , disease-specific and generic quality of life , health and social services re source use and their costs . RESULTS A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001 . Of the 1091 patients with proximal stenosis of the LAD , 127 were eligible and consented to take part ; 100 were r and omised and the remaining 27 consented to follow-up . All r and omised participants were included in an intention-to-treat analysis of survival free from cardiac-related events , which found a non-significant benefit from MIDCAB .  Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2 % for MIDCAB and PTCA , respectively . There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life . The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA , respectively . The costs of re sources used during 1 year of follow-up were 1033 British pounds and 843 British pounds , respectively . CONCLUSIONS The study found no evidence that MIDCAB was more effective than PTCA . The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA . Given these findings , it is unlikely that MIDCAB represents a cost-effective use of re sources in the reference population . Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB . At the same time , cardiologists are treating more patients with multi-vessel disease by PTCA . Future primary research should focus on this comparison . Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review BACKGROUND Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established . METHODS We r and omly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy . Primary end points were the rate of death and a composite of death , myocardial infa rct ion , or stroke ( major cardiovascular events ) . R and omization was stratified according to the choice of percutaneous coronary intervention ( PCI ) or coronary-artery bypass grafting ( CABG ) as the more appropriate intervention . RESULTS At 5 years , rates of survival did not differ significantly between the revascularization group ( 88.3 % ) and the medical-therapy group ( 87.8 % , P=0.97 ) or between the insulin-sensitization group ( 88.2 % ) and the insulin-provision group ( 87.9 % , P=0.89 ) . The rates of freedom from major cardiovascular events also did not differ significantly among the groups : 77.2 % in the revascularization group and 75.9 % in the medical-treatment 
    Output:
    
Conclusions Economic evaluations of RCTs in the 2012 ACC/AHA ischemic heart disease guideline largely had high QHES scores but method ological issues existed among “ high‐ quality ” studies .