***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: CONTEXT Many patients with chronic angina experience anginal episodes despite revascularization and antianginal medications . In a previous trial , antianginal monotherapy with ranolazine , a drug believed to partially inhibit fatty acid oxidation , increased treadmill exercise performance ; however , its long-term efficacy and safety have not been studied in combination with beta-blockers or calcium antagonists in a large patient population with severe chronic angina . OBJECTIVES To determine whether , at trough levels , ranolazine improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking st and ard doses of atenolol , amlodipine , or diltiazem  and to determine times to angina onset and to electrocardiographic evidence of myocardial ischemia , effect on angina attacks and nitroglycerin use , and effect on long-term survival in an open-label observational study extension . DESIGN , SETTING , AND PATIENTS A r and omized , 3-group parallel , double-blind , placebo-controlled trial of 823 eligible adults with symptomatic chronic angina who were r and omly assigned to receive placebo or 1 of 2 doses of ranolazine . Patients treated at the 118 participating ambulatory outpatient setting s in several countries were enrolled in the Combination Assessment of Ranolazine In Stable Angina ( CARISA ) trial from July 1999 to August 2001 and followed up through October 31 , 2002 . INTERVENTION Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine . Treadmill exercise 12 hours ( trough ) and 4 hours ( peak ) after dosing was assessed after 2 , 6 ( trough only ) , and 12 weeks of treatment . MAIN OUTCOME MEASURES Change in exercise duration , time to onset of angina , time to onset of ischemia , nitroglycerin use , and number of angina attacks . RESULTS Trough exercise duration increased by 115.6 seconds from baseline in both ranolazine groups ( pooled ) vs 91.7 seconds in the placebo group ( P = .01 ) . The times to angina and to electrocardiographic ischemia also increased in the ranolazine groups , at peak more than at trough . The increases did not depend on changes in blood pressure , heart rate , or background antianginal therapy and persisted throughout 12 weeks . Ranolazine reduced angina attacks and nitroglycerin use by about 1 per week vs placebo ( P<.02 ) . Survival of 750 patients taking ranolazine  during the CARISA trial or its associated long-term open-label study was 98.4 % in the first year and 95.9 % in the second year . CONCLUSION Twice-daily doses of ranolazine increased exercise capacity and provided additional antianginal relief to symptomatic patients with severe chronic angina taking st and ard doses of atenolol , amlodipine , or diltiazem , without evident adverse , long-term survival consequences over 1 to 2 years of therapy 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 group ( P=0.70 ) and 77.7 % in the insulin-sensitization group and 75.4 % in the insulin-provision group ( P=0.13 ) . In the PCI stratum , there was no significant difference in primary end points between the revascularization group and the medical-therapy group . In the CABG stratum , the rate of major cardiovascular events was significantly lower in the revascularization group ( 22.4 % ) than in the medical-therapy group ( 30.5 % , P=0.01 ; P=0.002 for interaction between stratum and study group ) . Adverse events and serious adverse events were generally similar among the groups , although severe hypoglycemia was more frequent in the insulin-provision group ( 9.2 % ) than in the insulin-sensitization group ( 5.9 % , P=0.003 ) . CONCLUSIONS Overall , there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision . ( Clinical Trials.gov number , NCT00006305 . OBJECTIVES The primary objective of the Monotherapy Assessment of Ranolazine In Stable Angina ( MARISA ) trial was to determine the dose-response relationship of ranolazine , a potentially new anti-anginal compound , on symptom-limited exercise duration . BACKGROUND Fatty acids rise precipitously in response to stress , including acute myocardial ischemia . Ranolazine is believed to partially inhibit fatty acid oxidation , shift metabolism toward carbohydrate oxidation , and increase the efficiency of oxygen use . METHODS Patients ( n = 191 ) with angina-limited exercise discontinued anti-anginal medications and were r and omized into a double-blind four-period crossover study of sustained-release ranolazine 500 , 1,000 , or 1,500 mg , or placebo , each administered twice daily for one week . Exercise testing was performed at the end of each treatment during both trough and peak ranolazine plasma concentrations . RESULTS Exercise duration at trough increased with ranolazine 500 , 1,000 , and 1,500 mg twice daily by 94 , 103 , and 116 s , respectively , all greater ( p < 0.005 ) than the 70-s increase on placebo . Dose-related increases in exercise duration at peak and in times to 1 mm ST-segment depression at trough and peak and to angina at trough and peak were also demonstrated ( all p < 0.005 ) . Ranolazine had negligible effects on heart rate and blood pressure . One year survival rate combining data from the MARISA trial and its open-label follow-on study was 96.3 + /- 1.7 % . CONCLUSIONS In chronic angina patients , ranolazine monotherapy was well tolerated and increased exercise performance throughout its dosing interval at all doses studied without clinical ly meaningful hemodynamic effects . One-year survival was not lower than expected in this high-risk patient population . This metabolic approach to treating myocardial ischemia may offer a new therapeutic option for chronic angina patients OBJECTIVES This study sought to determine whether initial medical therapy ( MT ) only or percutaneous coronary intervention plus medical therapy ( PCI+MT ) is better for patients with low-risk stable coronary artery disease ( CAD ) indicated for intervention in Japan . BACKGROUND Several multicenter studies have suggested that in the above patients , an initial management strategy of PCI+MT does not reduce the long-term risk of cardiovascular events more effectively than initial MT only . METHODS We conducted a r and omized comparative study ( JSAP [ Japanese Stable Angina Pectoris ] study ) in the previously mentioned patients . RESULTS The patients were r and omized to PCI+MT ( n = 192 ) or initial MT only group ( n = 192 ) , and the patient characteristics were very similar in the 2 groups . During the 3.3-year follow-up , there was no significant difference in the cumulative death rate  between PCI+MT ( 2.9 % ) and MT ( 3.9 % ) . However , the cumulative risk of death plus acute coronary syndrome was significantly smaller in PCI+MT . CONCLUSIONS In stable low-risk CAD , PCI+MT may improve long-term prognosis more effectively than MT Background Detection of asymptomatic ischemia in patients with coronary artery disease has been associated with increased risk for adverse outcome , but treatment of patients with asymptomatic ischemia remains controversial . Accordingly , the purpose of this study was to determine if treatment reduces adverse outcome in patients with daily life ischemia . Methods and Results A multicenter , r and omized , double-blind , placebo- controlled study of asymptomatic or minimally symptomatic out patients with daily life silent ischemia due to coronary artery disease was conducted . The primary outcome measure was event- free survival at 1 year by Kaplan-Meier analysis . Events were death , resuscitated ventricular tachycardia/ fibrillation , myocardial infa rct ion , hospitalization for unstable angina , aggravation of angina , or revascularization . The secondary outcome was ischemia during ambulatory ECG monitoring at 4 weeks . Three hundred six out patients with mild or no angina ( Canadian Cardiovascular Society class I or II ) , abnormal exercise tests , and ischemia on ambulatory monitoring were r and omized to receive either atenolol ( 100 mg/d ) or placebo . After 4 weeks of treatment , the number ( mean±SD , 3.6±4.2 versus 1.7±4.6 episodes , P<.001 ) and average duration ( 30±3.3 versus 16.4 + 6.7 minutes , P<.001 ) of ischemic episodes per 48 hours of ambulatory monitoring decreased in atenolol- compared with placebo-assigned patients ( 4.4±4.6 to 3.1±6.0 episodes and 36.6±4.1 to 30±5.5 minutes ) . Event-free survival improved in atenolol-treated patients ( P<.0066 ) , who had an increased time to onset of first adverse event ( 120 versus 79 days ) and fewer total first events compared with placebo ( relative risk , 0.44 ; 95 % confidence intervals , 0.26 to 0.75 ; P=.001 ) . There was a nonsignificant trend for fewer serious events ( death , resuscitation from ventricular tachycardia/fibrillation , nonfatal myocardial infa rct ion , or hospitalization for unstable angina ) in atenolol-treated patients ( relative risk , 0.55 ; 95 % confidence intervals , 0.22 to 1.33 ; P=.175 ) . The most powerful univariate and multivariate correlate of event-free survival was absence of ischemia on ambulatory monitoring at 4 weeks . Side effects were mild and generally similar comparing atenolol- and placebo-treated patients , although bradycardia was more frequent with atenolol . Conclusions Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo Background —Percutaneous transluminal coronary angioplasty of the infa rct -related artery in stable survivors of acute myocardial infa rct ion is often performed , even in patients without any symptoms or residual ischemia . Despite the lack of r and omized studies , it is widely believed that this intervention will improve the clinical outcome of these patients . Methods and Results —Three hundred patients with single vessel disease of the infa rct vessel and no or minor angina pectoris in the subacute phase ( 1 to 6 weeks ) after an acute myocardial infa rct ion were r and omized to angioplasty ( n=149 ) or medical therapy ( n=151 ) . Primary end point was the survival free of reinfa rct ion , (re)intervention , coronary artery bypass surgery , or readmission for severe angina pectoris at 1 year . The event-free survival at 1 year was 82 % in the medical group and 90 % in the angioplasty group ( P = 0.06 ) . This difference was mainly driven by the difference in the need for ( re ) interventions ( 20 versus 8 , P = 0.03 ) . At long-term follow-up ( mean , 56 months ) , survival was 89 % and 96 % ( P = 0.02 ) . Survival free of reinfa rct ion , (re)intervention , or coronary artery bypass surgery was 66 % and 80 % in the medically and interventionally treated patients , respectively ( P = 0.05 ) . The use of nitrates was significantly lower in the angioplasty group , both at 1 year ( 38 % versus 67 % , P = 0.001 ) and at long-term follow-up ( 36 % versus 55 % , P = 0.006 ) . Conclusions —Percutaneous revascularization of the infa rct -related coronary artery in stable patients with single vessel disease improves clinical outcome at long-term follow-up and reduces 
    Output:
    
The most commonly used antianginal agents ( beta-blockers , nitrates , calcium channel blockers , and ranolazine ) demonstrated equivalent efficacy in improving patient reported ischemic symptoms and quantitative exercise parameters .
With regards to mortality , beta-blockers are beneficial in the setting of depressed left ventricular systolic function .
In contrast , recent evidence points toward the lack of similar benefit of beta-blockers in patients with preserved systolic function , even in the setting of prior myocardial infa rct ion .
No survival benefit has been identified with the use of calcium channel blockers , nitrates , or ranolazine .