human
***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 Several studies have indicated that treatment with angiotensin converting enzyme ( ACE ) inhibitors and angiotensin II type 1 receptor blockers ( ARBs ) may reduce the incidence of atrial fibrillation ( AF ) in hypertensive patients and patients with left ventricular dysfunction . However , there is limited data on the effect of ACE-inhibitors and ARBs in patients undergoing electrical cardioversion for persistent AF . We hypothesized that treatment with the ARB c and esartan , without adjunct antiarrhythmic therapy , would reduce the recurrence rate of AF after successful cardioversion . METHODS In a double blind , placebo-controlled study , 171 patients with persistent AF were r and omized to receive c and esartan 8 mg once daily ( n=86 ) or placebo ( n=85 ) for 3 - 6 weeks before and c and esartan 16 mg once daily or placebo for 6 months after electrical cardioversion . Primary endpoint was recurrence of AF . RESULTS A total of 68 patients in the c and esartan group and 69 patients in the placebo group were successfully cardioverted . Forty-eight patients ( 71 % ) in the c and esartan group and 45 ( 65 % ) in the placebo group had a recurrence of AF during 6 months follow-up . Median time to recurrence was 8 and 9 days in the c and esartan and placebo groups , respectively . The differences between the groups were not statistically significant . CONCLUSION Treatment with the ARB c and esartan for 3 - 6 weeks before and 6 months after electrical cardioversion had no effect on the recurrence rate of AF Background Although previous clinical trials demonstrated the non-inferiority of a rate control to rhythm control strategy for management of atrial fibrillation ( AF ) , the optimal treatment strategy for paroxysmal AF ( PAF ) remains unclear . Methods and Results A r and omized , multicenter comparison of rate control vs rhythm control in Japanese patients with PAF ( the Japanese Rhythm Management Trial for Atrial Fibrillation ( J-RHYTHM ) study ) was conducted . The primary endpoint was a composite of total mortality , symptomatic cerebral infa rct ion , systemic embolism , major bleeding , hospitalization for heart failure , or physical/psychological disability requiring alteration of treatment strategy . In the study , 823 patients with PAF were followed for a mean period of 578 days . The primary endpoint occurred in 64 patients ( 15.3 % ) assigned to rhythm control and in 89 patients ( 22.0 % ) to rate control ( P=0.0128 ) . No significant differences between the treatment strategies were observed in the incidences of death , stroke , bleeding and heart failure . Meanwhile , significantly fewer patients requested changes of assigned treatment strategy in the rhythm control vs the rate control group , which was accompanied by improvement in AF-specific quality of life scores . Conclusion The J-RHYTHM study showed that rhythm control was associated with fewer primary endpoints than rate control . However , mortality and cardiovascular morbidity were not affected by the treatment strategy ( umin-CTR No. C000000106 ) The aim of this study was to compare the effect of valsartan/amlodipine and atenolol/amlodipine combination in preventing the recurrence of atrial fibrillation ( AF ) in hypertensive diabetic patients with a history of recent paroxysmal atrial fibrillation . Two hundred ninty-six hypertensive patients with well-controlled type 2 diabetes in sinus rhythm but with at least 2 ECG-documented episodes of AF in the previous 6 months were r and omized to 160 mg of valsartan plus amlodipine ( titrated from 2.5 to 10 mg ) or to 100 mg of atenolol plus amlodipine ( 2.5 to 10 mg ) in addition to their previous antiarrhythmic treatment ( if any ) and were followed up for 1 year . Blood pressure ( BP ) and a 24-hour ECG were evaluated monthly . The patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible . SBP/DBP values were significantly reduced after 12 months with valsartan/amlodipine ( from 150.4/93.5 to 126.37/7.4 mm Hg , P < 0.001 ) and atenolol/amlodipine ( from 151.1/94.2 to 127.1/77.9 mm Hg , P < 0.001 ) , with no difference between the 2 regimens . At least 1 ECG-documented episode of AF was reported in 20.3 % of the patients treated with valsartan/amlodipine and in 34.1 % of those treated with atenolol/amlodipine , with a significant difference between treatments ( P < 0.01 ) . The positive effect of valsartan/amlodipine combination on AF recurrence was more evident in patients treated with amiodarone or propafenone than in patients treated with other antiarrhythmic drugs or without antiarrhythmic treatment . Despite similar BP reduction , valsartan/amlodipine combination was more effective in patients treated with amiodarone or propafenone than atenolol/amlodipine in preventing new episodes of AF in hypertensive diabetic patients BACKGROUND Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects .  Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects . METHODS In two identical multicenter , double-blind , r and omized trials , one conducted in Europe ( Clinical Trials.gov number , NCT00259428 [ Clinical Trials.gov ] ) and one conducted in the United States , Canada , Australia , South Africa , and Argentina ( termed the non-European trial , NCT00259376 [ Clinical Trials.gov ] ) , we evaluated the efficacy of dronedarone , with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo .  Rhythm was monitored transtelephonically on days 2 , 3 , and 5 ; at 3 , 5 , 7 , and 10 months ; during recurrence of arrhythmia ; and at nine scheduled visits during a 12-month period . The primary end point was the time to the first recurrence of atrial fibrillation or flutter . RESULTS In the European trial , the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group ( P=0.01 ) . The corresponding duration s in the non-European trial were 59 and 158 days ( P=0.002 ) . At the recurrence of arrhythmia in the European trial , the mean ( + /-SD ) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group ( P<0.001 ) ; the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute ( P<0.001 ) . Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group . CONCLUSIONS Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia BACKGROUND Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation . METHODS We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death . Patients were r and omly assigned to receive dronedarone , 400 mg twice a day , or placebo . The primary outcome was the first hospitalization due to cardiovascular events or death . Secondary outcomes were death from any cause , death from cardiovascular causes , and hospitalization due to cardiovascular events . RESULTS The mean follow-up period was 21+/-5 months , with the study drug discontinued prematurely in 696 of the 2301 patients ( 30.2 % ) receiving dronedarone and in 716 of the 2327 patients ( 30.8 % ) receiving placebo , mostly because of adverse events . The primary outcome occurred in 734 patients ( 31.9 % ) in the dronedarone group and in 917 patients ( 39.4 % ) in the placebo group , with a hazard ratio for dronedarone of 0.76 ( 95 % confidence interval [ CI ] , 0.69 to 0.84 ; P<0.001 ) . There were 116 deaths ( 5.0 % ) in the dronedarone group and 139 ( 6.0 % ) in the placebo group ( hazard ratio , 0.84 ; 95 % CI , 0.66 to 1.08 ; P=0.18 ) . There were 63 deaths from cardiovascular causes ( 2.7 % ) in the dronedarone group and 90 ( 3.9 % ) in the placebo group ( hazard ratio , 0.71 ; 95 % CI , 0.51 to 0.98 ; P=0.03 ) , largely due to a reduction in the rate of death from arrhythmia with dronedarone . The dronedarone group had higher rates of bradycardia , QT-interval prolongation , nausea , diarrhea , rash , and an increased serum creatinine level than the placebo group . Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups . CONCLUSIONS Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation . ( Clinical Trials.gov number , NCT00174785 . Background —In patients with left ventricular dysfunction , atrial fibrillation and flutter ( AF and AFl , respectively ) are common arrhythmias associated with increased morbidity and mortality . The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm , which might reduce mortality and hospitalizations . Methods and Results —In the Danish Investigations of Arrhythmia and Mortality ON  Dofetilide  ( DIAMOND ) studies , 506 patients were in AF-AFl at baseline . Over the course of study , cardioversion occurred in 148 ( 59 % ) dofetilide- and 86 ( 34 % ) placebo-treated patients . In these patients , the probability of maintaining sinus rhythm for 1 year was 79 % with dofetilide versus 42 % with placebo ( P < 0.001 ) . Dofetilide had no effect on all-cause mortality , but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality ( risk ratio [ RR ] , 0.44 ; 95 % CI , 0.30 to 0.64;P < 0.0001 ) . In addition , dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause ( RR , 0.70 ; 95 % CI , 0.56 to 0.89;P ≤0.005 ) or congestive heart failure ( RR , 0.69 ; 95 % CI , 0.51 to 0.93;P ≤0.02 ) rehospitalization . Conclusions —Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease . The present study suggests that restoration of sinus rhythm is associated with improved survival BACKGROUND Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone , but it does not contain iodine and thus does not cause iodine-related adverse reactions . Therefore , it may be of value in the treatment of patients with heart failure . METHODS In a multicenter study with a double-blind design , we planned to r and omly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of  dronedarone twice a day or placebo . The primary end point was the composite of death from any cause or hospitalization for heart failure . RESULTS After inclusion of 627 patients ( 310 in the dronedarone group and 317 in the placebo group ) , the trial was prematurely terminated for safety reasons , at the recommendation of the data and safety monitoring board , in accordance with the board 's predefined rules for termination of the study . During a median follow-up of 2 months , 25 patients in the dronedarone group ( 8.1 % ) and 12 patients in the placebo group ( 3.8 % ) died ( hazard ratio in the dronedarone group , 2.13 ; 95 % confidence interval [ CI ] , 1.07 to 4.25 ; P=0.03 ) . The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group . The primary end point did not differ significantly between the two groups ; there were 53 events in the dronedarone group ( 17.1 % ) and 40 events in the placebo group (  
    Output:
    
agent
In patients with AF and HF , rate control compared with rhythm control showed inferior risk of hospitalisation
***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 Several studies have indicated that treatment with angiotensin converting enzyme ( ACE ) inhibitors and angiotensin II type 1 receptor blockers ( ARBs ) may reduce the incidence of atrial fibrillation ( AF ) in hypertensive patients and patients with left ventricular dysfunction . However , there is limited data on the effect of ACE-inhibitors and ARBs in patients undergoing electrical cardioversion for persistent AF . We hypothesized that treatment with the ARB c and esartan , without adjunct antiarrhythmic therapy , would reduce the recurrence rate of AF after successful cardioversion . METHODS In a double blind , placebo-controlled study , 171 patients with persistent AF were r and omized to receive c and esartan 8 mg once daily ( n=86 ) or placebo ( n=85 ) for 3 - 6 weeks before and c and esartan 16 mg once daily or placebo for 6 months after electrical cardioversion . Primary endpoint was recurrence of AF . RESULTS A total of 68 patients in the c and esartan group and 69 patients in the placebo group were successfully cardioverted . Forty-eight patients ( 71 % ) in the c and esartan group and 45 ( 65 % ) in the placebo group had a recurrence of AF during 6 months follow-up . Median time to recurrence was 8 and 9 days in the c and esartan and placebo groups , respectively . The differences between the groups were not statistically significant . CONCLUSION Treatment with the ARB c and esartan for 3 - 6 weeks before and 6 months after electrical cardioversion had no effect on the recurrence rate of AF Background Although previous clinical trials demonstrated the non-inferiority of a rate control to rhythm control strategy for management of atrial fibrillation ( AF ) , the optimal treatment strategy for paroxysmal AF ( PAF ) remains unclear . Methods and Results A r and omized , multicenter comparison of rate control vs rhythm control in Japanese patients with PAF ( the Japanese Rhythm Management Trial for Atrial Fibrillation ( J-RHYTHM ) study ) was conducted . The primary endpoint was a composite of total mortality , symptomatic cerebral infa rct ion , systemic embolism , major bleeding , hospitalization for heart failure , or physical/psychological disability requiring alteration of treatment strategy . In the study , 823 patients with PAF were followed for a mean period of 578 days . The primary endpoint occurred in 64 patients ( 15.3 % ) assigned to rhythm control and in 89 patients ( 22.0 % ) to rate control ( P=0.0128 ) . No significant differences between the treatment strategies were observed in the incidences of death , stroke , bleeding and heart failure . Meanwhile , significantly fewer patients requested changes of assigned treatment strategy in the rhythm control vs the rate control group , which was accompanied by improvement in AF-specific quality of life scores . Conclusion The J-RHYTHM study showed that rhythm control was associated with fewer primary endpoints than rate control . However , mortality and cardiovascular morbidity were not affected by the treatment strategy ( umin-CTR No. C000000106 ) The aim of this study was to compare the effect of valsartan/amlodipine and atenolol/amlodipine combination in preventing the recurrence of atrial fibrillation ( AF ) in hypertensive diabetic patients with a history of recent paroxysmal atrial fibrillation . Two hundred ninty-six hypertensive patients with well-controlled type 2 diabetes in sinus rhythm but with at least 2 ECG-documented episodes of AF in the previous 6 months were r and omized to 160 mg of valsartan plus amlodipine ( titrated from 2.5 to 10 mg ) or to 100 mg of atenolol plus amlodipine ( 2.5 to 10 mg ) in addition to their previous antiarrhythmic treatment ( if any ) and were followed up for 1 year . Blood pressure ( BP ) and a 24-hour ECG were evaluated monthly . The patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible . SBP/DBP values were significantly reduced after 12 months with valsartan/amlodipine ( from 150.4/93.5 to 126.37/7.4 mm Hg , P < 0.001 ) and atenolol/amlodipine ( from 151.1/94.2 to 127.1/77.9 mm Hg , P < 0.001 ) , with no difference between the 2 regimens . At least 1 ECG-documented episode of AF was reported in 20.3 % of the patients treated with valsartan/amlodipine and in 34.1 % of those treated with atenolol/amlodipine , with a significant difference between treatments ( P < 0.01 ) . The positive effect of valsartan/amlodipine combination on AF recurrence was more evident in patients treated with amiodarone or propafenone than in patients treated with other antiarrhythmic drugs or without antiarrhythmic treatment . Despite similar BP reduction , valsartan/amlodipine combination was more effective in patients treated with amiodarone or propafenone than atenolol/amlodipine in preventing new episodes of AF in hypertensive diabetic patients BACKGROUND Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects .  Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects . METHODS In two identical multicenter , double-blind , r and omized trials , one conducted in Europe ( Clinical Trials.gov number , NCT00259428 [ Clinical Trials.gov ] ) and one conducted in the United States , Canada , Australia , South Africa , and Argentina ( termed the non-European trial , NCT00259376 [ Clinical Trials.gov ] ) , we evaluated the efficacy of dronedarone , with 828 patients receiving 400 mg of the drug twice daily and 409 patients receiving placebo .  Rhythm was monitored transtelephonically on days 2 , 3 , and 5 ; at 3 , 5 , 7 , and 10 months ; during recurrence of arrhythmia ; and at nine scheduled visits during a 12-month period . The primary end point was the time to the first recurrence of atrial fibrillation or flutter . RESULTS In the European trial , the median times to the recurrence of arrhythmia were 41 days in the placebo group and 96 days in the dronedarone group ( P=0.01 ) . The corresponding duration s in the non-European trial were 59 and 158 days ( P=0.002 ) . At the recurrence of arrhythmia in the European trial , the mean ( + /-SD ) ventricular rate was 117.5+/-29.1 beats per minute in the placebo group and 102.3+/-24.7 beats per minute in the dronedarone group ( P<0.001 ) ; the corresponding rates in the non-European trial were 116.6+/-31.9 and 104.6+/-27.1 beats per minute ( P<0.001 ) . Rates of pulmonary toxic effects and of thyroid and liver dysfunction were not significantly increased in the dronedarone group . CONCLUSIONS Dronedarone was significantly more effective than placebo in maintaining sinus rhythm and in reducing the ventricular rate during recurrence of arrhythmia BACKGROUND Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation . METHODS We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death . Patients were r and omly assigned to receive dronedarone , 400 mg twice a day , or placebo . The primary outcome was the first hospitalization due to cardiovascular events or death . Secondary outcomes were death from any cause , death from cardiovascular causes , and hospitalization due to cardiovascular events . RESULTS The mean follow-up period was 21+/-5 months , with the study drug discontinued prematurely in 696 of the 2301 patients ( 30.2 % ) receiving dronedarone and in 716 of the 2327 patients ( 30.8 % ) receiving placebo , mostly because of adverse events . The primary outcome occurred in 734 patients ( 31.9 % ) in the dronedarone group and in 917 patients ( 39.4 % ) in the placebo group , with a hazard ratio for dronedarone of 0.76 ( 95 % confidence interval [ CI ] , 0.69 to 0.84 ; P<0.001 ) . There were 116 deaths ( 5.0 % ) in the dronedarone group and 139 ( 6.0 % ) in the placebo group ( hazard ratio , 0.84 ; 95 % CI , 0.66 to 1.08 ; P=0.18 ) . There were 63 deaths from cardiovascular causes ( 2.7 % ) in the dronedarone group and 90 ( 3.9 % ) in the placebo group ( hazard ratio , 0.71 ; 95 % CI , 0.51 to 0.98 ; P=0.03 ) , largely due to a reduction in the rate of death from arrhythmia with dronedarone . The dronedarone group had higher rates of bradycardia , QT-interval prolongation , nausea , diarrhea , rash , and an increased serum creatinine level than the placebo group . Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups . CONCLUSIONS Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation . ( Clinical Trials.gov number , NCT00174785 . Background —In patients with left ventricular dysfunction , atrial fibrillation and flutter ( AF and AFl , respectively ) are common arrhythmias associated with increased morbidity and mortality . The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm , which might reduce mortality and hospitalizations . Methods and Results —In the Danish Investigations of Arrhythmia and Mortality ON  Dofetilide  ( DIAMOND ) studies , 506 patients were in AF-AFl at baseline . Over the course of study , cardioversion occurred in 148 ( 59 % ) dofetilide- and 86 ( 34 % ) placebo-treated patients . In these patients , the probability of maintaining sinus rhythm for 1 year was 79 % with dofetilide versus 42 % with placebo ( P < 0.001 ) . Dofetilide had no effect on all-cause mortality , but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality ( risk ratio [ RR ] , 0.44 ; 95 % CI , 0.30 to 0.64;P < 0.0001 ) . In addition , dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause ( RR , 0.70 ; 95 % CI , 0.56 to 0.89;P ≤0.005 ) or congestive heart failure ( RR , 0.69 ; 95 % CI , 0.51 to 0.93;P ≤0.02 ) rehospitalization . Conclusions —Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease . The present study suggests that restoration of sinus rhythm is associated with improved survival BACKGROUND Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone , but it does not contain iodine and thus does not cause iodine-related adverse reactions . Therefore , it may be of value in the treatment of patients with heart failure . METHODS In a multicenter study with a double-blind design , we planned to r and omly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of  dronedarone twice a day or placebo . The primary end point was the composite of death from any cause or hospitalization for heart failure . RESULTS After inclusion of 627 patients ( 310 in the dronedarone group and 317 in the placebo group ) , the trial was prematurely terminated for safety reasons , at the recommendation of the data and safety monitoring board , in accordance with the board 's predefined rules for termination of the study . During a median follow-up of 2 months , 25 patients in the dronedarone group ( 8.1 % ) and 12 patients in the placebo group ( 3.8 % ) died ( hazard ratio in the dronedarone group , 2.13 ; 95 % confidence interval [ CI ] , 1.07 to 4.25 ; P=0.03 ) . The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group . The primary end point did not differ significantly between the two groups ; there were 53 events in the dronedarone group ( 17.1 % ) and 40 events in the placebo group (  
    Output:
    