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: Regression of hypertensive left ventricular hypertrophy ( LVH ) is associated with improved prognosis . The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension . Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information , both methods were applied in this trial . In the r and omized , double-blind , multicenter trial CardioVascular Irbesartan Project , 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months . Voltage criteria used for LVH were Sokolow index , Cornell index , Cornell voltage × QRS duration product and Lewis index . In parallel , left ventricular mass ( LVM ) was determined by 2-dimensional guided M-mode echocardiography . After 6 and 18 months , reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan . However , a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall . In contrast , reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits . In conclusion , treatment of hypertension with irbesartan result ed in a significant reduction in the voltage criteria for LVH , although an effect on LVM was only seen in subjects with high baseline LVM . In contrast , atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH . Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM , we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment Background — Heart failure ( HF ) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction ( PEF [ ≥50 % ] or REF [ < 50 % ] ) . In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , 42 418 high-risk hypertensive patients were r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin , providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF . Methods and Results — HF diagnostic criteria were prespecified in the ALLHAT protocol . EF estimated by contrast ventriculography , echocardiography , or radionuclide study was available in 910 of 1367 patients ( 66.6 % ) with hospitalized events meeting ALLHAT criteria . Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF ( overall and by PEF and REF ) . HF case fatality rates were examined . Of those with EF data , 44.4 % had HFPEF and 55.6 % had HFREF . Chlorthalidone reduced the risk of HFPEF compared with amlodipine , lisinopril , or doxazosin ; the hazard ratios were 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ; P=0.009 ) , 0.74 ( 95 % CI , 0.56 to 0.97 ; P=0.032 ) , and 0.53 ( 95 % CI , 0.38 to 0.73 ; P<0.001 ) , respectively . Chlorthalidone  reduced the risk of HFREF compared with amlodipine or doxazosin ; the hazard ratios were 0.74 ( 95 % CI , 0.59 to 0.94 ; P=0.013 ) and 0.61 ( 95 % CI , 0.47 to 0.79 ; P<0.001 ) , respectively . Chlorthalidone was similar to lisinopril with regard to incidence of HFREF ( hazard ratio , 1.07 ; 95 % CI , 0.82 to 1.40 ; P=0.596 ) . After HF onset , death occurred in 29.2 % of participants ( chlorthalidone/amlodipine/lisinopril ) with new-onset HFPEF versus 41.9 % in those with HFREF ( P<0.001 ; median follow-up , 1.74 years ) ; and in the chlorthalidone/doxazosin comparison that was terminated early , 20.0 % of HFPEF and 26.0 % of HFREF patients died ( P=0.185 ; median follow-up , 1.55 years ) . Conclusions — In ALLHAT , with adjudicated outcomes , chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin . Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril . Among high-risk hypertensive men and women , HFPEF has a better prognosis than HFREF BACKGROUND The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear . In prespecified analyses , we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients . METHODS As part of the LIFE study , in a double-masked , r and omised , parallel-group trial , we assigned a group of 1195 patients with diabetes , hypertension , and signs of left-ventricular hypertrophy ( LVH ) on electrocardiograms losartan-based or atenolol-based treatment . Mean age of patients was 67 years ( SD 7 ) and mean blood pressure 177/96 mm Hg ( 14/10 ) after placebo run-in . We followed up patients for at least 4 years ( mean 4.7 years [ 1.1 ] ) . We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality ( cardiovascular death , stroke , or myocardial infa rct ion ) . FINDINGS Mean blood pressure fell to 146/79 mm Hg ( 17/11 ) in losartan patients and 148/79 mm Hg ( 19/11 ) in atenolol patients . The primary endpoint occurred in 103 patients assigned losartan ( n=586 ) and 139 assigned atenolol ( n=609 ) ; relative risk 0.76 ( 95 % CI 0.58-.98 ) , p=0.031 . 38 and 61 patients in the losartan and atenolol groups , respectively , died from cardiovascular disease ; 0.63 ( 0.42 - 0.95 ) , p=0.028 . Mortality from all causes was 63 and 104 in losartan and atenolol groups , respectively ; 0.61 ( 0.45 - 0.84 ) , p=0.002 . INTERPRETATION Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension , diabetes , and LVH . Losartan seems to have benefits beyond blood pressure reduction In the main Valsartan Antihypertensive Long-Term Use Evaluation ( VALUE ) report , we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens .  In this report , we analyzed outcomes in 7080 patients ( 46.4 % ) who , at the end of the initial drug adjustment period ( 6 months ) , remained on monotherapy .  Baseline characteristics were similar in the  valsartan ( N=3263 ) and amlodipine ( N=3817 ) groups . Time on monotherapy was 3.2 years ( 78 % of treatment exposure time ) . The average in-trial blood pressure was similar in both groups . Event rates in the monotherapy group were 16 % to 39 % lower than in the main VALUE trial . In the first analysis , we censored patients when they discontinued monotherapy ( “ censored ” ) ; in the second , we counted events regardless of subsequent therapy ( intention-to-treat principle ) . We also assessed the impact of duration of monotherapy on outcomes . No difference was found in primary composite cardiac end points , strokes , myocardial infa rct ions , and all-cause deaths with both analyses . Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses ( hazard ratios : 0.63 , P=0.004 and 0.78 , P=0.045 , respectively ) . Longer duration of monotherapy amplified between-group differences in heart failure . New-onset diabetes was lower in the valsartan group with both analyses ( odds ratios : 0.78 , P=0.012 and 0.82 , P=0.034 ) . Thus , despite lower absolute event rates in monotherapy patients , the relative risks of heart failure and new-onset diabetes favored valsartan . Moreover , these findings support the feasibility of comparative prospect i ve trials in lower-risk hypertensive patients Hypertension is associated with reduced coronary vasodilatory capacity , possibly caused by structural changes in the coronary resistance vessels . Because vasodilatory treatment may correct abnormal structure better than nonvasodilating treatment , we compared whether long-term angiotensin-converting enzyme ( ACE ) inhibition has a greater effect on coronary reserve and cardiovascular structure than & bgr;-blockade in patients with essential hypertension . Thirty previously untreated hypertensive patients were r and omized in a double-blind design to treatment for 1 year with either perindopril ( 4 to 8 mg per day , n=15 ) or atenolol ( 50 to 100 mg per day , n=15 ) and furthermore compared with normotensive controls . Cardiac output and left ventricular mass were measured with echocardiography and resistance artery structure was determined in vitro . Using positron emission tomography , myocardial perfusion ( MP ) was determined at rest and during dipyridamole-induced hyperemia while still on medication . Perindopril  reduced left ventricular mass by 14±4 % ( P<0.01 ) , peripheral vascular resistance by 12±6 % ( P<0.01 ) , and media thickness-to-lumen diameter ratio of resistance arteries by 16±4 % ( P<0.05 ) , whereas atenolol had no effect . Resting MP was decreased both by perindopril ( −11±4 % , P<0.01 ) and by atenolol ( −25±4 % , P<0.01 ) in parallel to the reduction in rate pressure product . Hyperemic MP was unaltered by perindopril ( + 2±6 % , P = NS ) , but reduced by atenolol ( −32±5 % , P<0.01 ) . Compared with atenolol , perindopril treatment result ed in higher coronary reserve ( P<0.05 ) . We conclude that compared with & bgr;-blockade , ACE inhibition increases coronary reserve and results in regression of hypertensive resistance artery structure and left ventricular hypertrophy . Vasodilating may thus be superior to nonvasodilating treatment in repairing the hypertensive myocardial microcirculation The Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the & bgr;-blocker atenolol . We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates . Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy , r and om allocation to losartan-based treatment lowered the risk of fatal ( hazard ratio [ HR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.43 to 0.96 ; P=0.032 ) and atherothrombotic stroke ( HR , 0.72 ; 95 % CI , 0.59 to 0.88 ; P=0.001 ) compared with atenolol-based therapy . Although comparable risk reductions occurred for hemorrhagic and embolic stroke , these were not statistically significant . The number of neurological deficits per stroke was similar , but there were fewer strokes in the losartan group for nearly every level of stroke severity . Effects were consistent in all clinical subgroups except for those defined by age and ethnicity . The benefits of losartan on all strokes were independent of baseline and time-varying risk factors , including blood pressure . The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant , declining to 25 , 24 , and 9 for patients with cerebrovascular disease , isolated systolic hypertension , and atrial fibrillation , respectively . In conclusion , substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the ren 
    Output:
    
agent
We found predominantly moderate quality evidence that all-cause mortality is similar when first-line RAS inhibitors are compared to other first-line antihypertensive agents .
First-line thiazides caused less HF and stroke than first-line RAS inhibitors .
Compared with first-line CCBs , first-line RAS inhibitors reduced HF but increased stroke .
The magnitude of the reduction in HF exceeded the increase in stroke .
The small differences in effect on blood pressure between the different classes of drugs did not correlate with the differences in the primary outcomes
***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: Regression of hypertensive left ventricular hypertrophy ( LVH ) is associated with improved prognosis . The aim of this trial was to compare the effects of irbesartan versus atenolol on LVH in subjects with essential hypertension . Because electrocardiographic and echocardiographic parameters of LVH carry disparate prognostic information , both methods were applied in this trial . In the r and omized , double-blind , multicenter trial CardioVascular Irbesartan Project , 240 patients with essential hypertension were treated with irbesartan or atenolol for 18 months . Voltage criteria used for LVH were Sokolow index , Cornell index , Cornell voltage × QRS duration product and Lewis index . In parallel , left ventricular mass ( LVM ) was determined by 2-dimensional guided M-mode echocardiography . After 6 and 18 months , reductions of LVM and voltage criteria for LVH were only found in subjects treated with irbesartan . However , a reduction of LVM was only detectable in subjects within the highest quartile of baseline LVM but not overall . In contrast , reductions of voltage criteria for LVH were detectable after 6 and 18 months even within commonly used normal limits . In conclusion , treatment of hypertension with irbesartan result ed in a significant reduction in the voltage criteria for LVH , although an effect on LVM was only seen in subjects with high baseline LVM . In contrast , atenolol did not lead to reductions in electrocardiographic or echocardiographic parameters of LVH . Because voltage criteria for LVH have been shown to predict cardiovascular outcome independently from LVM , we suggest that both methods should be used to accurately assess the benefits of antihypertensive treatment Background — Heart failure ( HF ) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction ( PEF [ ≥50 % ] or REF [ < 50 % ] ) . In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , 42 418 high-risk hypertensive patients were r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin , providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF . Methods and Results — HF diagnostic criteria were prespecified in the ALLHAT protocol . EF estimated by contrast ventriculography , echocardiography , or radionuclide study was available in 910 of 1367 patients ( 66.6 % ) with hospitalized events meeting ALLHAT criteria . Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF ( overall and by PEF and REF ) . HF case fatality rates were examined . Of those with EF data , 44.4 % had HFPEF and 55.6 % had HFREF . Chlorthalidone reduced the risk of HFPEF compared with amlodipine , lisinopril , or doxazosin ; the hazard ratios were 0.69 ( 95 % confidence interval [ CI ] , 0.53 to 0.91 ; P=0.009 ) , 0.74 ( 95 % CI , 0.56 to 0.97 ; P=0.032 ) , and 0.53 ( 95 % CI , 0.38 to 0.73 ; P<0.001 ) , respectively . Chlorthalidone  reduced the risk of HFREF compared with amlodipine or doxazosin ; the hazard ratios were 0.74 ( 95 % CI , 0.59 to 0.94 ; P=0.013 ) and 0.61 ( 95 % CI , 0.47 to 0.79 ; P<0.001 ) , respectively . Chlorthalidone was similar to lisinopril with regard to incidence of HFREF ( hazard ratio , 1.07 ; 95 % CI , 0.82 to 1.40 ; P=0.596 ) . After HF onset , death occurred in 29.2 % of participants ( chlorthalidone/amlodipine/lisinopril ) with new-onset HFPEF versus 41.9 % in those with HFREF ( P<0.001 ; median follow-up , 1.74 years ) ; and in the chlorthalidone/doxazosin comparison that was terminated early , 20.0 % of HFPEF and 26.0 % of HFREF patients died ( P=0.185 ; median follow-up , 1.55 years ) . Conclusions — In ALLHAT , with adjudicated outcomes , chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin . Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril . Among high-risk hypertensive men and women , HFPEF has a better prognosis than HFREF BACKGROUND The most suitable antihypertensive drug to reduce the risk of cardiovascular disease in patients with hypertension and diabetes is unclear . In prespecified analyses , we compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in diabetic patients . METHODS As part of the LIFE study , in a double-masked , r and omised , parallel-group trial , we assigned a group of 1195 patients with diabetes , hypertension , and signs of left-ventricular hypertrophy ( LVH ) on electrocardiograms losartan-based or atenolol-based treatment . Mean age of patients was 67 years ( SD 7 ) and mean blood pressure 177/96 mm Hg ( 14/10 ) after placebo run-in . We followed up patients for at least 4 years ( mean 4.7 years [ 1.1 ] ) . We used Cox regression analysis with baseline Framingham risk score and electrocardiogram-LVH as covariates to compare the effects of the drugs on the primary composite endpoint of cardiovascular morbidity and mortality ( cardiovascular death , stroke , or myocardial infa rct ion ) . FINDINGS Mean blood pressure fell to 146/79 mm Hg ( 17/11 ) in losartan patients and 148/79 mm Hg ( 19/11 ) in atenolol patients . The primary endpoint occurred in 103 patients assigned losartan ( n=586 ) and 139 assigned atenolol ( n=609 ) ; relative risk 0.76 ( 95 % CI 0.58-.98 ) , p=0.031 . 38 and 61 patients in the losartan and atenolol groups , respectively , died from cardiovascular disease ; 0.63 ( 0.42 - 0.95 ) , p=0.028 . Mortality from all causes was 63 and 104 in losartan and atenolol groups , respectively ; 0.61 ( 0.45 - 0.84 ) , p=0.002 . INTERPRETATION Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension , diabetes , and LVH . Losartan seems to have benefits beyond blood pressure reduction In the main Valsartan Antihypertensive Long-Term Use Evaluation ( VALUE ) report , we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens .  In this report , we analyzed outcomes in 7080 patients ( 46.4 % ) who , at the end of the initial drug adjustment period ( 6 months ) , remained on monotherapy .  Baseline characteristics were similar in the  valsartan ( N=3263 ) and amlodipine ( N=3817 ) groups . Time on monotherapy was 3.2 years ( 78 % of treatment exposure time ) . The average in-trial blood pressure was similar in both groups . Event rates in the monotherapy group were 16 % to 39 % lower than in the main VALUE trial . In the first analysis , we censored patients when they discontinued monotherapy ( “ censored ” ) ; in the second , we counted events regardless of subsequent therapy ( intention-to-treat principle ) . We also assessed the impact of duration of monotherapy on outcomes . No difference was found in primary composite cardiac end points , strokes , myocardial infa rct ions , and all-cause deaths with both analyses . Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses ( hazard ratios : 0.63 , P=0.004 and 0.78 , P=0.045 , respectively ) . Longer duration of monotherapy amplified between-group differences in heart failure . New-onset diabetes was lower in the valsartan group with both analyses ( odds ratios : 0.78 , P=0.012 and 0.82 , P=0.034 ) . Thus , despite lower absolute event rates in monotherapy patients , the relative risks of heart failure and new-onset diabetes favored valsartan . Moreover , these findings support the feasibility of comparative prospect i ve trials in lower-risk hypertensive patients Hypertension is associated with reduced coronary vasodilatory capacity , possibly caused by structural changes in the coronary resistance vessels . Because vasodilatory treatment may correct abnormal structure better than nonvasodilating treatment , we compared whether long-term angiotensin-converting enzyme ( ACE ) inhibition has a greater effect on coronary reserve and cardiovascular structure than & bgr;-blockade in patients with essential hypertension . Thirty previously untreated hypertensive patients were r and omized in a double-blind design to treatment for 1 year with either perindopril ( 4 to 8 mg per day , n=15 ) or atenolol ( 50 to 100 mg per day , n=15 ) and furthermore compared with normotensive controls . Cardiac output and left ventricular mass were measured with echocardiography and resistance artery structure was determined in vitro . Using positron emission tomography , myocardial perfusion ( MP ) was determined at rest and during dipyridamole-induced hyperemia while still on medication . Perindopril  reduced left ventricular mass by 14±4 % ( P<0.01 ) , peripheral vascular resistance by 12±6 % ( P<0.01 ) , and media thickness-to-lumen diameter ratio of resistance arteries by 16±4 % ( P<0.05 ) , whereas atenolol had no effect . Resting MP was decreased both by perindopril ( −11±4 % , P<0.01 ) and by atenolol ( −25±4 % , P<0.01 ) in parallel to the reduction in rate pressure product . Hyperemic MP was unaltered by perindopril ( + 2±6 % , P = NS ) , but reduced by atenolol ( −32±5 % , P<0.01 ) . Compared with atenolol , perindopril treatment result ed in higher coronary reserve ( P<0.05 ) . We conclude that compared with & bgr;-blockade , ACE inhibition increases coronary reserve and results in regression of hypertensive resistance artery structure and left ventricular hypertrophy . Vasodilating may thus be superior to nonvasodilating treatment in repairing the hypertensive myocardial microcirculation The Losartan Intervention For Endpoint reduction in hypertension ( LIFE ) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the & bgr;-blocker atenolol . We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates . Among 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy , r and om allocation to losartan-based treatment lowered the risk of fatal ( hazard ratio [ HR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.43 to 0.96 ; P=0.032 ) and atherothrombotic stroke ( HR , 0.72 ; 95 % CI , 0.59 to 0.88 ; P=0.001 ) compared with atenolol-based therapy . Although comparable risk reductions occurred for hemorrhagic and embolic stroke , these were not statistically significant . The number of neurological deficits per stroke was similar , but there were fewer strokes in the losartan group for nearly every level of stroke severity . Effects were consistent in all clinical subgroups except for those defined by age and ethnicity . The benefits of losartan on all strokes were independent of baseline and time-varying risk factors , including blood pressure . The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant , declining to 25 , 24 , and 9 for patients with cerebrovascular disease , isolated systolic hypertension , and atrial fibrillation , respectively . In conclusion , substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the ren 
    Output:
    