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 Atrial fibrillation ( AF ) is a very common cardiac arrhythmia , and is associated with an increased mortality in patients with hypertension . Whether the best therapeutic approach for these patients is to restore sinus rhythm ( SR ) or to adequately control the ventricular rate is still controversial . The aim of this study is to compare both strategies in patients with hypertension . METHODS AND RESULTS Two hundred and twenty-one patients with hypertension and AF of duration > 48 h were r and omly assigned to either the rhythm ( n=155 ) or rate ( n=66 ) control group . Exercise capacity was improved in the rhythm control group in the 1st year of the study ( p<0.0001 ) . There were no statistically significant differences in the embolic event rate and the total mortality between the 2 groups at the end of the study ( p = NS ) . CONCLUSIONS Although restoring and maintaining SR had a beneficial effect on exercise capacity in patients with hypertension and AF , no significant difference was found in terms of the total mortality and the embolic event rates . Thus , rate control is an acceptable primary strategy in patients with AF and hypertension Recent trials have favoured ventricular rate control in atrial fibrillation ( AF ) management , however the present study investigated whether the restoration and maintenance of sinus rhythm with long-term anticoagulation therapy was superior in terms of embolic events and death in 534 patients with an AF duration > 48 h. Patients were r and omized and received sinus rhythm control with either aspirin ( group 1 ) or warfarin ( group 2 ) , or they were given ventricular rate control ( group 3 ) . Cardioversion to sinus rhythm was attempted in 425 patients and was successful in 387 ( 91.1 % ) of them . After 3 years ' follow-up there were 12 , two and 15 embolic events in groups 1 , 2 and 3 respectively ( significant difference between groups 1 and 2 , and 2 and 3 ) and overall mortalities were four , two and 12 , respectively ( significant difference between groups 2 and 3 ) . It is concluded that patients with an AF duration > 48 h might benefit considerably from sinus rhythm restoration and long-term warfarin therapy in terms of embolic events and mortality In a controlled study comprising 176 patients ,  quinidine in the form of Kinidin Durules was found to reduced significantly the recurrence of the atrial fibrillation  during a 1-year follow-up period after successful electric shock conversion . After one year , 51 per cent ( 52/101 ) of the patients in the quinidine group , and 28 per cent ( 21/75 ) in the control group remained in sinus rhythm ( P smaller than 0.001 ) . No less than 43 per cent of the patients converted to sinus rhythm during treatment with maintenance doses of quinidine sulphate before intended DC conversion . Gastrointestinal side-effects were not uncommon , and caused interruption of quinidine treatment in some cases We evaluated the efficacy and safety of azimilide , a new class III antiarrhythmic agent that blocks both the slow and fast components of the cardiac-delayed rectifier potassium currents in 4 r and omized , double-blind , placebo-controlled trials with similar protocol s. The purpose of this study was to assess the relation between dose and effect . A total of 1,380 patients with a documented history of symptomatic atrial fibrillation ( AF ) , atrial flutter , or both , were enrolled . After a 3-day loading period during which the assigned dose was given twice a day , subjects received placebo or azimilide ( 35 , 50 , 75 , 100 , or 125 mg once a day ) for the duration of the study period . The primary end point of the studies was the time to symptomatic arrhythmia recurrence with a transtelephonic electrocardiogram typical of AF , atrial flutter , or paroxysmal supraventricular tachycardia . For each study , Kaplan-Meier estimates of the median time to recurrence were computed for placebo and for each azimilide dose . Cox proportional-hazards modeling was used to estimate hazard ratios for each active dose . Each of the 2 highest azimilide doses ( 100 and 125 mg/day ) significantly prolonged the time to recurrence of arrhythmia . For the 100 mg/day dose , the hazard ratio was 1.34 , 95 % confidence interval 1.05 to 1.72 ; p = 0.02 . For the 125 mg/day dose , the hazard ratio was 1.32 , 95 % confidence interval 1.07 to 1.62 ; p = 0.01 . Patients with a history of either ischemic heart disease or congestive heart failure had a significantly greater treatment effect from azimilide than those without it . Torsades de Pointes occurred in 0.9 % of patients receiving either of the 2 effective doses . Thus , doses of azimilide < 100 mg/day are not effective for control of AF , whereas doses of 100 and 125 mg/day are effective with an acceptable risk of serious toxicity BACKGROUND Azimilide dihydrochloride ( azimilide ) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias . In patients with atrial fibrillation , it has shown excellent efficacy in some previous trials and minimal efficacy in others . METHODS Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter , r and omized , placebo-controlled clinical trial . Patients were admitted to a hospital and r and omly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily . Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital .  Recurrence of atrial fibrillation was documented by electrocardiogram . In the primary efficacy analysis , time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease . Safety was assessed as deaths , adverse events , and serious adverse events . RESULTS A total of 446 patients were r and omized in the study ; 314 were in the subgroup with structural heart disease . The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days , and the difference between treatments was not significant ( P = .4596 , n = 314 ) . The relative risk for recurrence ( placebo : azimilide ) was 1.104 ( 95 % CI 0.849 - 1.436 ) . There was 1 death in the placebo group and 3 in the azimilide group . CONCLUSIONS Azimilide did not demonstrate clinical ly important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm 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 —Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . This report describes the cause-specific modes of death in the AFFIRM treatment groups . Methods and Results —All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee , and a mode of death was assigned . In AFFIRM , 2033 patients were r and omized to a rhythm-control strategy and 2027 patients to a rate-control strategy .  During a mean follow-up of 3.5 years , there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients ( P = 0.07 ) . In the rhythm-control group , 129 patients ( 9 % ) died of a cardiac cause , and in the rate-control group , 130 patients ( 10 % ) died ( P = 0.95 ) . Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths . The numbers of vascular deaths were similar in the 2 groups : 35 ( 3 % ) in the rhythm-control group and 37 ( 3 % ) in the rate-control group ( P = 0.82 ) . There were no differences in the rates of ischemic stroke and central nervous system hemorrhage . In the rhythm-control group , there were 169 noncardiovascular deaths ( 47.5 % of the total number of deaths ) , whereas in the rate-control arm , there were 113 noncardiovascular deaths ( 36.5 % of the total number of deaths ) ( P = 0.0008 ) . Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths . Conclusions —Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate 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 
    Output:
    
agent
Assessment of the comparative effectiveness of individual AADs on CV hospitalization and mortality end points is not possible with the current evidence
***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 Atrial fibrillation ( AF ) is a very common cardiac arrhythmia , and is associated with an increased mortality in patients with hypertension . Whether the best therapeutic approach for these patients is to restore sinus rhythm ( SR ) or to adequately control the ventricular rate is still controversial . The aim of this study is to compare both strategies in patients with hypertension . METHODS AND RESULTS Two hundred and twenty-one patients with hypertension and AF of duration > 48 h were r and omly assigned to either the rhythm ( n=155 ) or rate ( n=66 ) control group . Exercise capacity was improved in the rhythm control group in the 1st year of the study ( p<0.0001 ) . There were no statistically significant differences in the embolic event rate and the total mortality between the 2 groups at the end of the study ( p = NS ) . CONCLUSIONS Although restoring and maintaining SR had a beneficial effect on exercise capacity in patients with hypertension and AF , no significant difference was found in terms of the total mortality and the embolic event rates . Thus , rate control is an acceptable primary strategy in patients with AF and hypertension Recent trials have favoured ventricular rate control in atrial fibrillation ( AF ) management , however the present study investigated whether the restoration and maintenance of sinus rhythm with long-term anticoagulation therapy was superior in terms of embolic events and death in 534 patients with an AF duration > 48 h. Patients were r and omized and received sinus rhythm control with either aspirin ( group 1 ) or warfarin ( group 2 ) , or they were given ventricular rate control ( group 3 ) . Cardioversion to sinus rhythm was attempted in 425 patients and was successful in 387 ( 91.1 % ) of them . After 3 years ' follow-up there were 12 , two and 15 embolic events in groups 1 , 2 and 3 respectively ( significant difference between groups 1 and 2 , and 2 and 3 ) and overall mortalities were four , two and 12 , respectively ( significant difference between groups 2 and 3 ) . It is concluded that patients with an AF duration > 48 h might benefit considerably from sinus rhythm restoration and long-term warfarin therapy in terms of embolic events and mortality In a controlled study comprising 176 patients ,  quinidine in the form of Kinidin Durules was found to reduced significantly the recurrence of the atrial fibrillation  during a 1-year follow-up period after successful electric shock conversion . After one year , 51 per cent ( 52/101 ) of the patients in the quinidine group , and 28 per cent ( 21/75 ) in the control group remained in sinus rhythm ( P smaller than 0.001 ) . No less than 43 per cent of the patients converted to sinus rhythm during treatment with maintenance doses of quinidine sulphate before intended DC conversion . Gastrointestinal side-effects were not uncommon , and caused interruption of quinidine treatment in some cases We evaluated the efficacy and safety of azimilide , a new class III antiarrhythmic agent that blocks both the slow and fast components of the cardiac-delayed rectifier potassium currents in 4 r and omized , double-blind , placebo-controlled trials with similar protocol s. The purpose of this study was to assess the relation between dose and effect . A total of 1,380 patients with a documented history of symptomatic atrial fibrillation ( AF ) , atrial flutter , or both , were enrolled . After a 3-day loading period during which the assigned dose was given twice a day , subjects received placebo or azimilide ( 35 , 50 , 75 , 100 , or 125 mg once a day ) for the duration of the study period . The primary end point of the studies was the time to symptomatic arrhythmia recurrence with a transtelephonic electrocardiogram typical of AF , atrial flutter , or paroxysmal supraventricular tachycardia . For each study , Kaplan-Meier estimates of the median time to recurrence were computed for placebo and for each azimilide dose . Cox proportional-hazards modeling was used to estimate hazard ratios for each active dose . Each of the 2 highest azimilide doses ( 100 and 125 mg/day ) significantly prolonged the time to recurrence of arrhythmia . For the 100 mg/day dose , the hazard ratio was 1.34 , 95 % confidence interval 1.05 to 1.72 ; p = 0.02 . For the 125 mg/day dose , the hazard ratio was 1.32 , 95 % confidence interval 1.07 to 1.62 ; p = 0.01 . Patients with a history of either ischemic heart disease or congestive heart failure had a significantly greater treatment effect from azimilide than those without it . Torsades de Pointes occurred in 0.9 % of patients receiving either of the 2 effective doses . Thus , doses of azimilide < 100 mg/day are not effective for control of AF , whereas doses of 100 and 125 mg/day are effective with an acceptable risk of serious toxicity BACKGROUND Azimilide dihydrochloride ( azimilide ) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias . In patients with atrial fibrillation , it has shown excellent efficacy in some previous trials and minimal efficacy in others . METHODS Patients who had symptomatic atrial fibrillation for > 48 hours but < 6 months were eligible for this multicenter , r and omized , placebo-controlled clinical trial . Patients were admitted to a hospital and r and omly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily . Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital .  Recurrence of atrial fibrillation was documented by electrocardiogram . In the primary efficacy analysis , time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease . Safety was assessed as deaths , adverse events , and serious adverse events . RESULTS A total of 446 patients were r and omized in the study ; 314 were in the subgroup with structural heart disease . The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days , and the difference between treatments was not significant ( P = .4596 , n = 314 ) . The relative risk for recurrence ( placebo : azimilide ) was 1.104 ( 95 % CI 0.849 - 1.436 ) . There was 1 death in the placebo group and 3 in the azimilide group . CONCLUSIONS Azimilide did not demonstrate clinical ly important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm 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 —Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . This report describes the cause-specific modes of death in the AFFIRM treatment groups . Methods and Results —All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee , and a mode of death was assigned . In AFFIRM , 2033 patients were r and omized to a rhythm-control strategy and 2027 patients to a rate-control strategy .  During a mean follow-up of 3.5 years , there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients ( P = 0.07 ) . In the rhythm-control group , 129 patients ( 9 % ) died of a cardiac cause , and in the rate-control group , 130 patients ( 10 % ) died ( P = 0.95 ) . Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths . The numbers of vascular deaths were similar in the 2 groups : 35 ( 3 % ) in the rhythm-control group and 37 ( 3 % ) in the rate-control group ( P = 0.82 ) . There were no differences in the rates of ischemic stroke and central nervous system hemorrhage . In the rhythm-control group , there were 169 noncardiovascular deaths ( 47.5 % of the total number of deaths ) , whereas in the rate-control arm , there were 113 noncardiovascular deaths ( 36.5 % of the total number of deaths ) ( P = 0.0008 ) . Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths . Conclusions —Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate 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 
    Output:
    