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: CONTEXT Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients , safety and efficacy of antihypertensive agents for coronary artery disease ( CAD ) have been discerned only from subgroup analyses in large trials . OBJECTIVE To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy ( CAS ) or a non-calcium antagonist strategy ( NCAS ) .  DESIGN , SETTING , AND PARTICIPANTS R and omized , open label , blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older , which was conducted September 1997 to February 2003 at 862 sites in 14 countries . INTERVENTIONS Patients were r and omly assigned to either CAS ( verapamil sustained release ) or NCAS ( atenolol ) . Strategies specified dose and additional drug regimens . Tr and olapril and /or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) of less than 140 mm Hg ( systolic ) and less than 90 mm Hg ( diastolic ) ; and less than 130 mm Hg ( systolic ) and less than 85 mm Hg ( diastolic ) if diabetes or renal impairment was present . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . MAIN OUTCOME MEASURES Primary : first occurrence of death ( all cause ) , nonfatal myocardial infa rct ion , or nonfatal stroke ; other : cardiovascular death , angina , adverse experiences , hospitalizations , and blood pressure control at 24 months . RESULTS At 24 months , in the CAS group , 6391 patients ( 81.5 % ) were taking verapamil sustained release ; 4934 ( 62.9 % ) were taking tr and olapril ; and 3430 ( 43.7 % ) were taking hydrochlorothiazide . In the NCAS group , 6083 patients ( 77.5 % ) were taking atenolol ; 4733 ( 60.3 % ) were taking hydrochlorothiazide ; and 4113 ( 52.4 % ) were taking tr and olapril . After a follow-up of 61 835 patient-years ( mean , 2.7 years per patient ) , 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies ( 9.93 % in CAS and 10.17 % in NCAS ; relative risk [ RR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) . Two-year blood pressure control was similar between groups . The JNC VI blood pressure goals were achieved by 65.0 % ( systolic ) and 88.5 % ( diastolic ) of CAS and 64.0 % ( systolic ) and 88.1 % ( diastolic ) of NCAS patients . A total of 71.7 % of CAS and 70.7 % of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg . CONCLUSION The verapamil-tr and olapril-based strategy was as clinical ly effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients Aims Whereas product labels of beta blockers list peripheral arterial disease ( PAD ) as a contraindication , current PAD guidelines state otherwise . We aim ed to evaluate the clinical efficacy and safety of the ß1 selective blocker nebivolol in hypertensive patients with PAD . Methods and results This multicentre , prospect i ve , double-blind , active controlled , parallel-group study compared once-daily treatment with nebivolol ( Neb ) 5 mg vs. hydrochlorothiazide ( HCTZ ) 25 mg , in hypertensive patients with Fontaine stage II ( intermittent claudication ) . The primary endpoint was the initial claudication distance ( ICD ) during treadmill exercise after 24-week treatment in the per protocol population , using a noninferiority statistical approach . A total of 177 patients ( mean age was 66.3 ± 9.2 years , 76.7 % men ) were r and omized to study treatment and 127 completed the study ; the intent-to-treat ( ITT ) analysis was performed on 163 patients , the per protocol analysis on 127 patients . Both drugs lowered blood pressure significantly . After 24-week treatment , ICD increased in the Neb group in the ITT population by 28.3 % ( 95 % CI 15.6–41.0 ) vs. in the HCTZ group by 26.5 % ( 14.4–38.5 ) , and in the per protocol population in the Neb group by 26.4 % ( 13.4–39.4 ) vs. in the HCTZ group by 32.1 % ( 18.4–45.7 ) . Thus , noninferiority of Neb could neither be confirmed nor rejected . An increase of absolute claudication distance ( ACD , mean percentage increase after 24 weeks on Neb 15.8 ± 33.2 vs. on HCTZ 20.2 ± 46.6 ) was observed without statistical differences between groups . Ankle-brachial index ( ABI ) increased slightly in both groups . Generally , both treatments were well tolerated . Conclusion The increases in ICD , ACD and ABI with nebivolol suggest that this medication does not have negative effects on hypertensive patients with symptomatic PAD , and can be used for treatment of hypertension in these patients at high cardiovascular risk without reducing the walking ability In a six month placebo-controlled cross-over trial twenty patients with hypertension and peripheral arterial disease were r and omised to captopril 25 mg twice daily , atenolol 100 mg once daily , labetalol 200 mg twice daily , or pindolol 10 mg twice daily for one month . Although all treatments were equally effective at lowering blood pressure , pain-free and maximum walking distances on a treadmill were decreased by  atenolol , labetalol , and  pindolol  , but not by captopril .  Post-exercise calf blood flow availability was impaired by  atenolol , labetalol , and  pindolol  , but not by captopril . Despite ancillary characteristics of cardioselectivity , intrinsic sympathomimetic activity , or combination with alpha-blockade , beta-blockers seem to impair the lower limb circulation in such patients , whereas captopril seems to preserve it , possibly by maintaining the collateral blood supply BACKGROUND Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were r and omly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril ( C 50 mg bid ) or Ticlopidine ( T 250 mg bid ) for three months and then with the association C plus T for three months again . After placebo administration for one month , patients were further treated with C plus T at low doses ( 25 mg bid and respectively 250 mg daily ) . In the first part of the study , patients of Group II received an inverse sequence of the drugs ( before Ticlopidine 250 mg bid and then Captopril 50 bid ) . In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD , TWD , and WI . T did not modify blood pressure but slightly increased PFWD , TWD , and WI . The improvement was more evident during administration of C plus T , whereas placebo administration induced a trend toward baseline values . Finally , the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters . In conclusion , chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication  , improving significantly PFWD and TWD Context Few therapies substantially reduce symptoms and improve exercise performance in patients with peripheral arterial disease ( PAD ) . Contribution In this double-blind trial , investigators r and omly assigned 40 older adults without diabetes and with symptomatic PAD to receive either ramipril or placebo , 10 mg once daily for 24 weeks . Compared with placebo , ramipril increased maximum and pain-free walking time and walking speed and distance . Caution s The trial was small and involved selected patients with limited mobility and exercise tolerance . Implication s Ramipril may improve symptoms in some patients with PAD . The Editors This article has been retracted . See Notice of Retraction . Peripheral arterial disease ( PAD ) is a common disorder , with 12 % of adults older than 50 years of age having an anklebrachial index ( ABI ) that is diagnostic of PAD ( < 0.9 ) ( 1 ) . Approximately one third of these patients experience intermittent claudication during walking , limiting normal activities . Medical treatments to improve walking distance are limited . The angiotensin-converting enzyme ( ACE ) inhibitor ramipril reduced cardiovascular morbidity and mortality compared with placebo in patients with established atherosclerotic disease , including PAD , in the Heart Outcomes Prevention Evaluation ( HOPE ) study ( 2 ) . This effect seemed to be independent of blood pressure reduction ( 3 ) and may relate to the known benefits of ACE inhibitors on both coronary and brachial endothelial function ( 4 ) . No previous controlled studies have investigated the effect of ACE inhibitors on symptoms of intermittent claudication . Given the positive effects of ramipril in the HOPE trial and its convenient once-daily dosing formulation , we hypothesized that therapy with ramipril would improve intermittent claudication symptoms . We aim ed to examine the effect of 6-month ramipril therapy on walking distance and claudication pain in a defined group of patients with claudication due to infrainguinal PAD by using a double-blind , r and omized , placebo-controlled design . Methods This article has been retracted . See Notice of Retraction . We screened 152 patients with PAD from general practice clinics in the Melbourne , Australia , metropolitan area ( Figure 1 ) . Of them , 40 patients ( mean age , 66 years [ SD , 4 ] ) were recruited and completed the trial . All patients gave written informed consent to participate in the study . The Ethics Committee of the Alfred Hospital , Melbourne , Australia , approved the study , and we performed the study in accordance with the Declaration of Helsinki 2000 . All participants had an ABI less than 0.9 at rest in at least 1 leg ; had a history of intermittent claudication ( unilateral or bilateral ) , which was stable for 6 months ; had evidence of superficial femoral artery stenosis or occlusion on duplex ultrasonography ; had blood pressure of 160 
    Output:
    
agent
However , lack of data specifically examining outcomes in PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure
***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 Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients , safety and efficacy of antihypertensive agents for coronary artery disease ( CAD ) have been discerned only from subgroup analyses in large trials . OBJECTIVE To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy ( CAS ) or a non-calcium antagonist strategy ( NCAS ) .  DESIGN , SETTING , AND PARTICIPANTS R and omized , open label , blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older , which was conducted September 1997 to February 2003 at 862 sites in 14 countries . INTERVENTIONS Patients were r and omly assigned to either CAS ( verapamil sustained release ) or NCAS ( atenolol ) . Strategies specified dose and additional drug regimens . Tr and olapril and /or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) of less than 140 mm Hg ( systolic ) and less than 90 mm Hg ( diastolic ) ; and less than 130 mm Hg ( systolic ) and less than 85 mm Hg ( diastolic ) if diabetes or renal impairment was present . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . MAIN OUTCOME MEASURES Primary : first occurrence of death ( all cause ) , nonfatal myocardial infa rct ion , or nonfatal stroke ; other : cardiovascular death , angina , adverse experiences , hospitalizations , and blood pressure control at 24 months . RESULTS At 24 months , in the CAS group , 6391 patients ( 81.5 % ) were taking verapamil sustained release ; 4934 ( 62.9 % ) were taking tr and olapril ; and 3430 ( 43.7 % ) were taking hydrochlorothiazide . In the NCAS group , 6083 patients ( 77.5 % ) were taking atenolol ; 4733 ( 60.3 % ) were taking hydrochlorothiazide ; and 4113 ( 52.4 % ) were taking tr and olapril . After a follow-up of 61 835 patient-years ( mean , 2.7 years per patient ) , 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies ( 9.93 % in CAS and 10.17 % in NCAS ; relative risk [ RR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) . Two-year blood pressure control was similar between groups . The JNC VI blood pressure goals were achieved by 65.0 % ( systolic ) and 88.5 % ( diastolic ) of CAS and 64.0 % ( systolic ) and 88.1 % ( diastolic ) of NCAS patients . A total of 71.7 % of CAS and 70.7 % of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg . CONCLUSION The verapamil-tr and olapril-based strategy was as clinical ly effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients Aims Whereas product labels of beta blockers list peripheral arterial disease ( PAD ) as a contraindication , current PAD guidelines state otherwise . We aim ed to evaluate the clinical efficacy and safety of the ß1 selective blocker nebivolol in hypertensive patients with PAD . Methods and results This multicentre , prospect i ve , double-blind , active controlled , parallel-group study compared once-daily treatment with nebivolol ( Neb ) 5 mg vs. hydrochlorothiazide ( HCTZ ) 25 mg , in hypertensive patients with Fontaine stage II ( intermittent claudication ) . The primary endpoint was the initial claudication distance ( ICD ) during treadmill exercise after 24-week treatment in the per protocol population , using a noninferiority statistical approach . A total of 177 patients ( mean age was 66.3 ± 9.2 years , 76.7 % men ) were r and omized to study treatment and 127 completed the study ; the intent-to-treat ( ITT ) analysis was performed on 163 patients , the per protocol analysis on 127 patients . Both drugs lowered blood pressure significantly . After 24-week treatment , ICD increased in the Neb group in the ITT population by 28.3 % ( 95 % CI 15.6–41.0 ) vs. in the HCTZ group by 26.5 % ( 14.4–38.5 ) , and in the per protocol population in the Neb group by 26.4 % ( 13.4–39.4 ) vs. in the HCTZ group by 32.1 % ( 18.4–45.7 ) . Thus , noninferiority of Neb could neither be confirmed nor rejected . An increase of absolute claudication distance ( ACD , mean percentage increase after 24 weeks on Neb 15.8 ± 33.2 vs. on HCTZ 20.2 ± 46.6 ) was observed without statistical differences between groups . Ankle-brachial index ( ABI ) increased slightly in both groups . Generally , both treatments were well tolerated . Conclusion The increases in ICD , ACD and ABI with nebivolol suggest that this medication does not have negative effects on hypertensive patients with symptomatic PAD , and can be used for treatment of hypertension in these patients at high cardiovascular risk without reducing the walking ability In a six month placebo-controlled cross-over trial twenty patients with hypertension and peripheral arterial disease were r and omised to captopril 25 mg twice daily , atenolol 100 mg once daily , labetalol 200 mg twice daily , or pindolol 10 mg twice daily for one month . Although all treatments were equally effective at lowering blood pressure , pain-free and maximum walking distances on a treadmill were decreased by  atenolol , labetalol , and  pindolol  , but not by captopril .  Post-exercise calf blood flow availability was impaired by  atenolol , labetalol , and  pindolol  , but not by captopril . Despite ancillary characteristics of cardioselectivity , intrinsic sympathomimetic activity , or combination with alpha-blockade , beta-blockers seem to impair the lower limb circulation in such patients , whereas captopril seems to preserve it , possibly by maintaining the collateral blood supply BACKGROUND Trials of beta blockers in patients undergoing non-cardiac surgery have reported conflicting results . This r and omised controlled trial , done in 190 hospitals in 23 countries , was design ed to investigate the effects of perioperative beta blockers . METHODS We r and omly assigned 8351 patients with , or at risk of , atherosclerotic disease who were undergoing non-cardiac surgery to receive extended-release metoprolol succinate ( n=4174 ) or placebo ( n=4177 ) , by a computerised r and omisation phone service . Study treatment was started 2 - 4 h before surgery and continued for 30 days . Patients , health-care providers , data collectors , and outcome adjudicators were masked to treatment allocation . The primary endpoint was a composite of cardiovascular death , non-fatal myocardial infa rct ion , and non-fatal cardiac arrest . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00182039 . FINDINGS All 8351 patients were included in analyses ; 8331 ( 99.8 % ) patients completed the 30-day follow-up . Fewer patients in the metoprolol group than in the placebo group reached the primary endpoint ( 244 [ 5.8 % ] patients in the metoprolol group vs 290 [ 6.9 % ] in the placebo group ; hazard ratio 0.84 , 95 % CI 0.70 - 0.99 ; p=0.0399 ) . Fewer patients in the metoprolol group than in the placebo group had a myocardial infa rct ion ( 176 [ 4.2 % ] vs 239 [ 5.7 % ] patients ; 0.73 , 0.60 - 0.89 ; p=0.0017 ) . However , there were more deaths in the metoprolol group than in the placebo group ( 129 [ 3.1 % ] vs 97 [ 2.3 % ] patients ; 1.33 , 1.03 - 1.74 ; p=0.0317 ) . More patients in the metoprolol group than in the placebo group had a stroke ( 41 [ 1.0 % ] vs 19 [ 0.5 % ] patients ; 2.17 , 1.26 - 3.74 ; p=0.0053 ) . INTERPRETATION Our results highlight the risk in assuming a perioperative beta-blocker regimen has benefit without substantial harm , and the importance and need for large r and omised trials in the perioperative setting . Patients are unlikely to accept the risks associated with perioperative extended-release metoprolol Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were r and omly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril ( C 50 mg bid ) or Ticlopidine ( T 250 mg bid ) for three months and then with the association C plus T for three months again . After placebo administration for one month , patients were further treated with C plus T at low doses ( 25 mg bid and respectively 250 mg daily ) . In the first part of the study , patients of Group II received an inverse sequence of the drugs ( before Ticlopidine 250 mg bid and then Captopril 50 bid ) . In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD , TWD , and WI . T did not modify blood pressure but slightly increased PFWD , TWD , and WI . The improvement was more evident during administration of C plus T , whereas placebo administration induced a trend toward baseline values . Finally , the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters . In conclusion , chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication  , improving significantly PFWD and TWD Context Few therapies substantially reduce symptoms and improve exercise performance in patients with peripheral arterial disease ( PAD ) . Contribution In this double-blind trial , investigators r and omly assigned 40 older adults without diabetes and with symptomatic PAD to receive either ramipril or placebo , 10 mg once daily for 24 weeks . Compared with placebo , ramipril increased maximum and pain-free walking time and walking speed and distance . Caution s The trial was small and involved selected patients with limited mobility and exercise tolerance . Implication s Ramipril may improve symptoms in some patients with PAD . The Editors This article has been retracted . See Notice of Retraction . Peripheral arterial disease ( PAD ) is a common disorder , with 12 % of adults older than 50 years of age having an anklebrachial index ( ABI ) that is diagnostic of PAD ( < 0.9 ) ( 1 ) . Approximately one third of these patients experience intermittent claudication during walking , limiting normal activities . Medical treatments to improve walking distance are limited . The angiotensin-converting enzyme ( ACE ) inhibitor ramipril reduced cardiovascular morbidity and mortality compared with placebo in patients with established atherosclerotic disease , including PAD , in the Heart Outcomes Prevention Evaluation ( HOPE ) study ( 2 ) . This effect seemed to be independent of blood pressure reduction ( 3 ) and may relate to the known benefits of ACE inhibitors on both coronary and brachial endothelial function ( 4 ) . No previous controlled studies have investigated the effect of ACE inhibitors on symptoms of intermittent claudication . Given the positive effects of ramipril in the HOPE trial and its convenient once-daily dosing formulation , we hypothesized that therapy with ramipril would improve intermittent claudication symptoms . We aim ed to examine the effect of 6-month ramipril therapy on walking distance and claudication pain in a defined group of patients with claudication due to infrainguinal PAD by using a double-blind , r and omized , placebo-controlled design . Methods This article has been retracted . See Notice of Retraction . We screened 152 patients with PAD from general practice clinics in the Melbourne , Australia , metropolitan area ( Figure 1 ) . Of them , 40 patients ( mean age , 66 years [ SD , 4 ] ) were recruited and completed the trial . All patients gave written informed consent to participate in the study . The Ethics Committee of the Alfred Hospital , Melbourne , Australia , approved the study , and we performed the study in accordance with the Declaration of Helsinki 2000 . All participants had an ABI less than 0.9 at rest in at least 1 leg ; had a history of intermittent claudication ( unilateral or bilateral ) , which was stable for 6 months ; had evidence of superficial femoral artery stenosis or occlusion on duplex ultrasonography ; had blood pressure of 160 
    Output:
    