***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: The Chinese Hypertension Intervention Efficacy Study ( CHIEF ) is a multi-centre r and omized controlled clinical trial comparing the effects of amlodipine+angiotensin II receptor blocker and amlodipine+diuretics on the incidence of cardiovascular events , represented as a composite of non-fatal stroke , non-fatal myocardial infa rct ion and cardiovascular death events in high-risk Chinese hypertensive patients . The study also evaluates the long-term effects of  lipid-lowering treatment and lifestyle modification .  From October 2007 to October 2008 , 13 542 patients were enrolled into the study in 180 centres in China . Patients will be followed up for 4 years . There was no difference in baseline characteristics between the two blood pressure arms Many patients with hypertension require ≥3 agents to achieve target blood pressure ( BP ) . The efficacy/safety of the dual combinations of valsartan (Val)/hydrochlorothiazide ( HCTZ ) and amlodipine (Aml)/Val in hypertension are well established . This r and omized , double-blind study evaluated the efficacy/safety of triple therapy with Aml/Val/HCTZ for moderate or severe hypertension ( mean sitting systolic BP : ≥145 mm Hg ; mean sitting diastolic BP : ≥100 mm Hg ) . The study included a single-blind , placebo run-in period , followed by double-blind treatment for 8 weeks ; patients were r and omly assigned to 1 of 4 groups titrated to Aml/Val/HCTZ 10/320/25 mg , Val/HCTZ 320/25 mg , Aml/Val 10/320 mg , or Aml/HCTZ 10/25 mg once daily . Dual-therapy recipients received half of the target doses of both agents for the first 2 weeks , titrating to target doses during week 3 . Those on triple therapy received Val/HCTZ 160.0/12.5 mg during week 1 , Aml/Val/HCTZ 5.0/160.0/12.5 mg during week 2 , and target doses of all 3 of the agents during week 3 . Of the 4285 patients enrolled , 2271 were r and omly assigned to treatment , and 2060 completed the study . Triple therapy was significantly superior to all of the dual therapies in reducing mean sitting systolic BP and mean sitting diastolic BP from baseline to end point ( all P<0.0001 ) . Significantly more patients on triple therapy achieved overall BP control ( < 140/90 mm Hg ; P<0.0001 ) and systolic and diastolic control ( P≤0.0002 ) compared with each dual therapy . Aml/Val/HCTZ was well tolerated . The benefits of triple therapy over dual therapy were observed regardless of age , sex , race , ethnicity , or baseline mean sitting systolic BP . In conclusion , this study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg The purpose of this study was to compare the combination treatments of manidipine/delapril and olmesartan/hydrochlorothiazide ( HCTZ ) in elderly diabetic hypertensives . After a 4-week placebo period , 158 hypertensive patients with type 2 diabetes ( age range : 66 to 74 years ) were r and omized to receive combination treatment of 10 mg manidipine plus 30 mg delapril or 20 mg olmesartan plus 12.5 mg HCTZ for 48 weeks in a prospect i ve , parallel arm trial . After 12 weeks , manidipine or HCTZ was doubled in nonresponders ( systolic blood pressure [ SBP ] ≥130 mmHg and /or diastolic blood pressure [ DBP ] ≥80 mmHg ) . Patients were checked at the end of the placebo period and every 12 weeks thereafter . At each visit , lying , sitting and st and ing BP as well as fasting glycemia , glycosylated hemoglobin ( HbA1c ) , electrolytes , uric acid , total cholesterol ( TC ) , high-density lipoprotein-cholesterol ( HDL-C ) and triglycerides ( TG ) were evaluated . Both combinations reduced sitting SBP ( −27.7 and −28.3 mmHg , respectively ; both p<0.001 ) and DBP ( −15.1 and −14.8 mmHg , respectively ; both p<0.01 ) with no difference between the two treatments . St and ing DBP was more markedly reduced by olmesartan/HCTZ ( −19.5 mmHg ; p<0.001 ) than by manidipine/delapril ( −14.7 mmHg ; p<0.05 vs. olmesartan/HCTZ ) . No changes in metabolic parameters were observed with manidipine/delapril , whereas an increase in HbA1c ( + 0.7 % ; p<0.05 ) , uric acid ( + 0.4 mg/dL ; p<0.05 ) and TG ( + 41.3 mg/dL ; p<0.05 ) , and a decrease in serum potassium ( −0.3 mmol/L ; p<0.05 ) and HDL-C ( −3.4 mg/dL ; p<0.05 ) were found in the olmesartan/HCTZ group . In conclusion , both combinations were similarly effective in reducing BP in elderly hypertensive diabetic patients .  However , manidipine/delapril offered some advantages in terms of the less-pronounced BP orthostatic changes and absence of metabolic adverse effects . ( Hypertens Res 2008 ; 31 : 43−50 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The & bgr;-blocker atenolol is less effective than angiotensin-receptor blockers and calcium-channel blockers for reducing central blood pressure ( BP ) . The trial was design ed to determine whether the advantages of angiotensin-receptor blockers over atenolol remained significant when both were combined with the calcium-channel blocker amlodipine . A prospect i ve , r and omized , blinded endpoint ( PROBE design ) parallel group , multicenter trial including 393 patients with essential hypertension resistant to 4 weeks of 5 mg of amlodipine  was set out . Central systolic BP , augmentation index ( AIx ; either rough or adjusted on heart rate ) , and carotid-to-femoral pulse wave velocity were measured with applanation tonometry ( SphygmoCor ) at inclusion and after 8 and 24 weeks of active treatment with an amlodipine-valsartan combination ( 5/80 mg and then 10/160 mg ) or an amlodipine-atenolol combination ( 5/50 mg and then 10/100 mg ) . From baseline to week 24 , central systolic BP decreased significantly more in the amlodipine-valsartan group ( −13.70±1.15 mm Hg ; P<0.0001 ) than in the amlodipine-atenolol group ( −9.70±1.10 mm Hg ; P<0.0001 ; difference : −4.00 mm Hg [ 95 % CI : −7.10 to −0.90 ] ; P=0.013 ) , despite similar changes in brachial systolic BP . The difference in rough AIx reduction was −6.5 % ( 95 % CI : −8.3 to −4.7 ; P<0.0001 ) in favor of amlodipine-valsartan  . AIx adjusted on heart rate was significantly reduced in favor of amlodipine-valsartan ( −2.8 % [ 95 % CI : −4.92 to −0.68 ] ; P<0.01 ) . Heart rate decreased significantly more with amlodipine-atenolol ( difference : −11 bpm [ 95 % CI : −14 to −8 bpm ] ; P<0.001 ) . Pulse wave velocity decreased by 0.95 m/s in both groups with no significant difference . Differences in central systolic BP and rough AIx remained significant after adjustment to the changes in heart rate . The amlodipine-valsartan  combination decreased central ( systolic and pulse ) pressure and AIx more than the amlodipine-atenolol combination Angiotensin receptor blockers ( ARBs ) with calcium channel blockers ( CCBs ) or diuretics are a widely used combination therapy for hypertensive patients . The present study aim ed to determine which combination was better for elderly hypertension patients aged ≧ 65 years . We design ed a multicentre , r and omized , open-label , parallel comparison study . Hypertensive out patients aged ≧ 65 years who did not achieve the target blood pressure ( BP < 140/90 mmHg ) with usual dosages of ARBs  were r and omly assigned to switch treatment to losartan 50 mg/hydrochlorothiazide 12.5 mg or amlodipine 5 mg in addition to ARBs . The primary endpoint was a change in the systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) after the 3-month treatment period , while secondary endpoints were changes in the BP , albuminuria , laboratory values , and cognitive function with the mini-mental state examination ( MMSE ) at baseline and after one year . The results from the CAMUI trial should provide new evidence for selecting optimal combination therapies for elderly hypertensive patients Objectives Current guidelines recommend the use of multiple medications for hypertension . The present study was aim ed at determining which combination was optimal to prevent cardiovascular events . Methods We conducted a prospect i ve , r and omized , open-label , blinded-endpoint trial . Hypertensive out patients aged between 40 and 85 years who did not achieve target blood pressure ( BP<140/90 mmHg ) with calcium channel blocker ( CCB ) benidipine 4 mg/day were r and omly assigned to receive angiotensin receptor blocker ( ARB ) , & bgr;-blocker , or thiazide diuretic in addition to benidipine . Results Among a total of 3501 patients ( 1167 , benidipine-ARB ; 1166 , benidipine-&bgr;-blocker ; and 1168 , benidipine-thiazide ) , 3293 patients ( 1110 , 1089 , and 1094 , respectively ) who received each combination treatment were included in the analysis . Median follow-up was 3.61 years . At the end of the treatment , 64.1 , 66.9 , and 66.0 % of patients in the benidipine-ARB , benidipine-&bgr;-blocker , and benidipine-thiazide groups achieved target BP , respectively . The cardiovascular composite endpoint occurred in 41 ( 3.7 % ) , 48 ( 4.4 % ) , and 32 ( 2.9 % ) patients , respectively : the hazard ratio was 1.26 in the benidipine-ARB ( P = 0.3505 ) and 1.54 in the benidipine-&bgr;-blocker ( P = 0.0567 ) groups compared with the benidipine-thiazide group . The secondary analyses revealed that benidipine and thiazide diuretic significantly reduced the incidence of fatal or nonfatal strokes ( P = 0.0109 ) and benidipine and ARB significantly reduced new-onset diabetes ( P = 0.0240 ) compared with benidipine and & bgr;-blocker . All trial treatments were safe and well tolerated . Conclusion CCB combined with ARB , & bgr;-blocker , or thiazide diuretic was similarly effective for the prevention of cardiovascular events and the achievement of target BP BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) 
    Output:
    
Our meta- analysis indicates that RASIs plus CCBs provide a superior safety and prevention of CV events to RASIs plus diuretics , whereas this combination is also safer than CCBs plus diuretics .