***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 Incomplete revascularisation is common after percutaneous coronary intervention and is associated with increased mortality and adverse cardiovascular events . We aim ed to assess whether adjunctive anti-ischaemic pharmacotherapy with ranolazine would improve the prognosis of patients with incomplete revascularisation after percutaneous coronary intervention . METHODS We performed this multicentre , r and omised , parallel-group , double-blind , placebo-controlled , event-driven trial at 245 centres in 15 countries in Europe , Israel , Russia , and the USA . Patients ( aged ≥18 years ) with a history of chronic angina with incomplete revascularisation after percutaneous coronary intervention ( defined as one or more lesions with ≥50 % diameter stenosis in a coronary artery ≥2 mm diameter ) were r and omly assigned ( 1:1 ) , via an interactive web-based block r and omisation system ( block sizes of ten ) , to receive either twice-daily oral ranolazine 1000 mg or matching placebo . R and omisation was stratified by diabetes history ( presence vs absence ) and acute coronary syndrome presentation ( acute coronary syndrome vs non-acute coronary syndrome ) . Study investigators , including all research teams , and patients were masked to treatment allocation . The primary endpoint was time to first occurrence of ischaemia-driven revascularisation or ischaemia-driven hospitalisation without revascularisation . Analysis was by intention to treat . This study is registered at Clinical Trials.gov , number NCT01442038 . FINDINGS Between Nov 3 , 2011 , and May 27 , 2013 , we r and omly assigned 2651 patients to receive ranolazine ( n=1332 ) or placebo ( n=1319 ) ; 2604 ( 98 % ) patients comprised the full analysis set . After a median follow-up of 643 days ( IQR 575 - 758 ) , the composite primary endpoint occurred in 345 ( 26 % ) patients assigned to ranolazine and 364 ( 28 % ) patients assigned to placebo ( hazard ratio 0·95 , 95 % CI 0·82 - 1·10 ; p=0·48 ) . Incidence of ischaemia-driven revascularisation and ischaemia-driven hospitalisation did not differ significantly between groups . 189 ( 14 % ) patients in the ranolazine group and 137 ( 11 % ) patients in the placebo group discontinued study drug because of an adverse event ( p=0·04 ) . INTERPRETATION Ranolazine did not reduce the composite rate of ischaemia-driven revascularisation or hospitalisation without revascularisation in patients with a history of chronic angina who had incomplete revascularisation after percutaneous coronary intervention . Further studies are warranted to establish whether other treatment could be effective in improving the prognosis of high-risk patients in this population . FUNDING Gilead Sciences , Menarini 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 Background Patients with ischemic cardiomyopathy ( ICM ) may continue to experience persistent chest pain and /or dyspnea despite pharmacologic therapy and revascularization . We hypothesized that ranolazine would reduce anginal symptoms or dyspnea in optimally treated ICM patients . Methods In this r and omized , double-blind , crossover- design pilot study , 28 patients with ICM ( ejection fraction less or equal 40 % ) were included after providing informed consent . A total of 24 patients completed both placebo and ranolazine treatments and were analyzed . All patients were on treatment with a  beta blocker  , an angiotensin-converting enzyme inhibitor ( or angiotensin receptor blocker ) , and at least one additional antianginal drug . After r and omization , patients received up to 1,000 mg ranolazine orally twice a day , as tolerated , versus placebo . The primary end point was change in angina as assessed by the Seattle Angina Question naire ( SAQ ) , or in dyspnea as assessed by the Rose Dyspnea Scale ( RDS ) . Change in the RDS and SAQ score from baseline was compared , for ranolazine and placebo , using the Wilcoxon signed rank test or paired t-test . Results Patients had the following demographic and clinical variables : mean age of 71.5 years ; male ( 82.1 % ) ; prior coronary bypass surgery ( 67.9 % ) ; prior coronary percutaneous intervention ( 85.7 % ) ; prior myocardial infa rct ion ( 82.1 % ) ; diabetes ( 67.9 % ) ; and mean ejection fraction of 33.1 % . No statistical difference was seen between baseline RDS score and that after placebo or ranolazine ( n=20 ) ( P≥0.05 ) . There was however , an improvement in anginal frequency ( 8/10 patients ) ( P=0.058 ) , quality of life ( 8/10 patients ) ( P=0.048 ) , and mean score of all components of the SAQ question naire ( n=10 ) ( P=0.047 ) with ranolazine compared with placebo . Conclusion In optimally treated ICM patients with continued chest pain or dyspnea , ranolazine possibly had a positive impact on quality of life , a reduction in anginal frequency , and an overall improvement in the mean SAQ component score compared with baseline . Ranolazine did not change the dyspnea score compared with baseline OBJECTIVES We conducted a pilot study for a large definitive clinical trial evaluating the impact of ranolazine in women with angina , evidence of myocardial ischemia , and no obstructive coronary artery disease ( CAD ) . BACKGROUND Women with angina , evidence of myocardial ischemia , but no obstructive CAD frequently have microvascular coronary dysfunction . The impact of ranolazine in this patient group is unknown . METHODS A pilot r and omized , double-blind , placebo-controlled , crossover trial was conducted in 20 women with angina , no obstructive CAD , and ≥ 10 % ischemic myocardium on adenosine stress cardiac magnetic resonance ( CMR ) imaging . Participants were assigned to ranolazine or placebo for 4 weeks separated by a 2-week washout . The Seattle Angina Question naire and CMR were evaluated after each treatment . Invasive coronary flow reserve ( CFR ) was available in patients who underwent clinical ly indicated coronary reactivity testing . CMR data analysis included the percentage of ischemic myocardium and quantitative myocardial perfusion reserve index ( MPRI ) . RESULTS The mean age of subjects was 57 ± 11 years . Compared with placebo , patients on ranolazine had significantly higher ( better ) Seattle Angina Question naire scores , including physical functioning ( p = 0.046 ) , angina stability ( p = 0.008 ) , and quality of life ( p = 0.021 ) . There was a trend toward a higher ( better ) CMR mid-ventricular MPRI ( 2.4 [ 2.0 minimum , 2.8 maximum ] vs. 2.1 [ 1.7 minimum , 2.5 maximum ] , p = 0.074 ) on ranolazine . Among women with coronary reactivity testing ( n = 13 ) , those with CFR ≤ 3.0 had a significantly improved MPRI  on ranolazine versus placebo compared to women with CFR > 3.0 ( Δ in MPRI 0.48 vs. -0.82 , p = 0.04 ) . CONCLUSIONS In women with angina , evidence of ischemia , and no obstructive CAD , this pilot r and omized , controlled trial revealed that ranolazine  improves angina . Myocardial ischemia may also improve , particularly among women with low CFR . These data document approach feasibility and provide outcome variability estimates for planning a definitive large clinical trial to evaluate the role of ranolazine in women with microvascular coronary dysfunction . ( Microvascular Coronary Disease In Women : Impact Of Ranolazine ; NCT00570089 ) OBJECTIVES The purpose of this study was to determine if ranolazine improves angina in stable coronary patients with persisting symptoms despite maximum recommended dose of amlodipine . BACKGROUND Ranolazine is a unique antianginal agent that has been effective in stable angina , but it has not been studied in the setting of maximum recommended doses of conventional antianginal agents . METHODS Stable patients with coronary disease and > or =3 anginal attacks per week despite maximum recommended dosage of amlodipine ( 10 mg/day ) were r and omized to 
    Output:
    
We found very low quality evidence showing that people with stable angina who received ranolazine  as monotherapy had increased risk of presenting non-serious adverse events compared to those given placebo .
We found low quality evidence indicating that people with stable  angina who received ranolazine showed uncertain effect on the risk of cardiovascular death ( for ranolazine given as monotherapy ) , all-cause death and non-fatal AMI , and the frequency of angina episodes ( for ranolazine given as monotherapy ) compared to those given placebo .
Moderate quality evidence indicated that people with stable angina who received ranolazine showed uncertain effect on quality of life compared with people who received placebo .
Moderate quality evidence also indicated that people with stable angina who received ranolazine as add-on therapy had fewer angina episodes but increased risk of presenting non-serious adverse events compared to those given placebo