***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 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 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 1,000 mg ranolazine or placebo twice a day for 6 weeks . Primary end point was the frequency of angina episodes per week during the double-blind treatment phase . Efficacy was also assessed by  nitroglycerin consumption per week and the Seattle Angina Question naire ( SAQ ) . Adjustment for multiple testing of secondary end points used a hierarchic closed testing procedure . Efficacy was assessed in subgroups based on baseline angina frequency , concomitant long-acting nitrate use , gender , and age . Safety was assessed by adverse events and electrocardiogram evaluations . RESULTS A total of 565 patients were r and omized : 281 patients to ranolazine and 284 patients to placebo .  Baseline characteristics were similar between treatment groups . At baseline , angina frequency averaged 5.63 + /- 0.18 episodes/week , and nitroglycerin consumption averaged 4.72 + /- 0.21 tablets/week . Compared with placebo , ranolazine significantly reduced frequency of angina episodes ( 2.88 + /- 0.19 on ranolazine vs. 3.31 + /- 0.22 on placebo ; p = 0.028 ) and nitroglycerin consumption ( 2.03 + /- 0.20 on ranolazine vs. 2.68 + /- 0.22 ; p = 0.014 ) , with treatment effect that appeared consistent across subgroups . The median angina weekly episode rate at baseline was 4.5 per week . Subgroup analysis showed statistically significant reductions of angina frequency , nitroglycerin use , and SAQ angina frequency for patients with a baseline frequency > 4.5 per week but only of angina frequency for those with baseline frequency < or = 4.5 per week . Patients with more frequent angina appeared to have a more pronounced treatment effect . No hemodynamic changes were observed . Ranolazine was well tolerated . CONCLUSIONS Ranolazine significantly reduced frequency of angina and nitroglycerin consumption compared with placebo and was well tolerated . ( The ERICA [ Efficacy of Ranolazine In Chronic Angina ] Trial ; http:// clinical trials.gov ; NCT00091429 ) Objectives To estimate the cost-effectiveness of ranolazine when added to st and ard-of-care ( SoC ) antianginals compared with SoC alone in patients with stable coronary disease experiencing ≥3 attacks/week . Setting An economic model utilising a UK health system perspective , a 1-month cycle-length and a 1-year time horizon . Participants Patients with stable coronary disease experiencing ≥3 attacks/week starting in 1 of 4 angina frequency health states based on Seattle Angina Question naire Angina Frequency ( SAQAF ) scores ( 100=no ; 61–99=monthly ; 31–60=weekly ; 0–30=daily angina ) . Intervention Ranolazine added to SoC or SoC alone . Patients were allowed to transition between SAQAF states ( first cycle only ) or death ( any cycle ) based on probabilities derived from the r and omised , controlled Efficacy of Ranolazine in Chronic Angina trial and other studies . Patients not responding to ranolazine in month 1 ( not improving ≥1 SAQAF health state ) discontinued ranolazine and were assumed to behave like SoC patients . Primary and secondary outcomes measures Costs ( £ 2014 ) and quality -adjusted life-years ( QALYs ) for patients receiving and not receiving ranolazine .  Results Ranolazine patients lived a mean of 0.701 QALYs at a cost of £ 5208 . Those not receiving ranolazine lived 0.662 QALYs at a cost of £ 5318 . The addition of ranolazine to SoC was therefore a dominant economic strategy . The incremental cost-effectiveness ratio was sensitive to ranolazine cost ; exceeding £ 20 000/QALY when ranolazine 's cost was > £ 203/month . Ranolazine remained a dominant strategy when indirect costs were included and mortality rates were assumed to increase with worsening severity of SAQAF health states . Monte Carlo simulation found ranolazine to be a dominant strategy in ∼71 % of 10 000 iterations . Conclusions Although UK-specific data on ranolazine 's efficacy and safety are lacking , our analysis suggest ranolazine added to SoC in patients with weekly or daily angina is likely cost-effective from a UK health system perspective CONTEXT Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes ( ACS ) . OBJECTIVE To determine the efficacy and safety of ranolazine during long-term treatment of patients with non-ST-elevation ACS . DESIGN , SETTING , AND PATIENTS A r and omized , double-blind , placebo-controlled , multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine ( initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily , n = 3279 ) or matching placebo ( n = 3281 ) , and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8 , 2004 , and February 14 , 2007 . MAIN OUTCOME MEASURES The primary efficacy end point was a composite of cardiovascular death , myocardial infa rct ion ( MI ) , or recurrent ischemia through the end of study . The major safety end points were death from any cause and symptomatic documented arrhythmia . RESULTS The primary end point occurred in 696 patients ( 21.8 % ) in the ranolazine group and 753 patients ( 23.5 % ) in the placebo group ( hazard ratio [ HR ] , 0.92 ; 95 % confidence interval [ CI ] , 0.83 - 1.02 ; P = .11 ) . The major secondary end point ( cardiovascular death , MI , or severe recurrent ischemia ) occurred in 602 patients ( 18.7 % ) in the ranolazine group and 625 ( 19.2 % ) in the placebo group ( HR , 0.96 ; 95 % CI , 0.86 - 1.08 ; P = .50 ) . Cardiovascular death or MI occurred in 338 patients ( 10.4 % ) allocated to ranolazine and 343 patients ( 10.5 % ) allocated to placebo ( HR , 0.99 ; 95 % CI , 0.85 - 1.15 ; P = .87 ) . Recurrent ischemia was reduced in the ranolazine group ( 430 [ 13.9 % ] ) compared with the placebo group ( 494 [ 16.1 % ] ; HR , 0.87 ; 95 % CI , 0.76 - 0.99 ; P = .03 ) . QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients ( 0.9 % ) receiving ranolazine compared with 10 patients ( 0.3 % ) receiving placebo .  Symptomatic documented arrhythmias did not differ between the ranolazine ( 99 [ 3.0 % ] ) and placebo ( 102 [ 3.1 % ] ) groups ( P = .84 ) . No difference in total mortality was observed with ranolazine compared with placebo ( 172 vs 175 ; HR , 0.99 ; 95 % CI , 0.80 - 1.22 ; P = .91 ) . CONCLUSIONS The addition of ranolazine to st and ard treatment for ACS was not effective in reducing major cardiovascular events .  Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia . Our findings provide support for the safety 
    Output:
    
Ranolazine appears to be dominant or cost-effective , mainly due to its ability to decrease angina-related hospitalizations and also due to a marginal improvement in quality of life .
The acquisition cost of ranolazine was the variable with the greatest impact upon the ICER .
The existing evidence , although limited , indicates that ranolazine may be a dominant or cost-effective therapy option , for the treatment of patients with symptomatic CSA .