***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: Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients .  Chlorthalidone has significantly reduced stroke and cardiovascular end points in several l and mark trials ; however , hydrochlorothiazide remains favored in practice . Most clinicians assume that the drugs are interchangeable , but their antihypertensive effects at lower doses have not been directly compared . We conducted a r and omized , single-blinded , 8-week active treatment , crossover study comparing chlorthalidone 12.5 mg/day ( force-titrated to 25 mg/day ) and hydrochlorothiazide 25 mg/day ( force-titrated to 50 mg/day ) in untreated hypertensive patients . The main outcome , 24-hour ambulatory blood pressure ( BP ) monitoring , was assessed at baseline and week 8 , along with st and ard office BP readings every 2 weeks . Thirty patients completed the first active treatment period , whereas 24 patients completed both . An order – drug – time interaction was observed with chlorthalidone ; therefore , data from only the first active treatment period was considered . Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP  with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day ( 24-hour mean = −12.4±1.8 mm Hg versus −7.4±1.7 mm Hg ; P=0.054 ; nighttime mean = −13.5±1.9 mm Hg versus −6.4±1.8 mm Hg ; P=0.009 ) . Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day ( −15.7±2.2 mm Hg versus −4.5±2.1 mm Hg ; P=0.001 ) ; however , by week 8 , reductions were statistically similar ( −17.1±3.7 versus −10.8±3.5 ; P=0.84 ) . Within recommended doses , chlorthalidone is more effective in lowering systolic BPs  than hydrochlorothiazide , as evidence d by 24-hour ambulatory BPs . These differences were not apparent with office BP measurements CONTEXT Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme ( ACE ) inhibitors or calcium channel blockers ( CCBs ) . OBJECTIVE To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease ( CVD ) incidence in racial subgroups . DESIGN , SETTING , AND PARTICIPANTS Prespecified subgroup analysis of ALLHAT , a r and omized , double-blind , active-controlled , clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older ( 35 % black ) with at least 1 other cardiovascular risk factor . INTERVENTIONS Antihypertensive regimens initiated with a CCB ( amlodipine ) or an ACE inhibitor ( lisinopril ) vs a thiazide-type diuretic ( chlorthalidone ) . Other medications were added to achieve goal blood pressures ( BPs ) less than 140/90 mm Hg . MAIN OUTCOME MEASURES The primary outcome was combined fatal coronary heart disease ( CHD ) or nonfatal myocardial infa rct ion ( MI ) , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , heart failure [ HF ] , or peripheral vascular disease ) , and end-stage renal disease . RESULTS No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup . For amlodipine vs chlorthalidone only , HF was the only prespecified clinical outcome that differed significantly ( overall : relative risk [ RR ] , 1.37 ; 95 % confidence interval [ CI ] , 1.24 - 1.51 ; blacks : RR , 1.46 ; 95 % CI , 1.24 - 1.73 ; nonblacks : RR , 1.32 ; 95 % CI , 1.17 - 1.49 ; P<.001 for each comparison ) with no difference in treatment effects by race ( P = .38 for interaction ) . For lisinopril vs chlorthalidone , results differed by race for systolic BP ( greater decrease in blacks with chlorthalidone ) , stroke , and combined CVD outcomes ( P<.001 , P = .01 , and P = .04 , respectively , for interactions ) . In blacks and nonblacks , respectively , the RRs for stroke were 1.40 ( 95 % CI , 1.17 - 1.68 ) and 1.00 ( 95 % CI , 0.85 - 1.17 ) and for combined CVD were 1.19 ( 95 % CI , 1.09 - 1.30 ) and 1.06 ( 95 % CI , 1.00 - 1.13 ) . For HF , the RRs were 1.30 ( 95 % CI , 1.10 - 1.54 ) and 1.13 ( 95 % CI , 1.00 - 1.28 ) , with no significant interaction by race . Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks . CONCLUSIONS In blacks and nonblack subgroups , rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome , and diuretic-based treatment result ed in the lowest risk of heart failure . While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks , thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients BACKGROUND Sulfhydryl angiotensin-converting enzyme ( ACE ) inhibitors exert antiatherosclerotic effects in pre clinical models and antioxidant effects in patients . However , whether ACE inhibitors have any clinical ly significant antiatherogenic effects remains still debated . OBJECTIVES In mildly hypertensive patients , we evaluated the effect of the sulfhydryl ACE inhibitor zofenopril in comparison with the carboxylic ACE inhibitor enalapril on carotid atherosclerosis ( intima-media thickness [ IMT ] and vascular lumen diameter ) and systemic oxidative stress ( nitrite/nitrate , asymmetrical dimethyl-l-arginine , and isoprostanes ) . METHODS In 2001 , we started a small prospect i ve r and omized clinical trial on 48 newly diagnosed mildly hypertensive patients with no additional risk factors for atherosclerosis ( eg , hyperlipidemia , smoke habit , familiar history of atherosclerosis-related diseases or diabetes ) . Patients were r and omly assigned either to the enalapril ( 20 mg/d , n = 24 ) or the zofenopril group ( 30 mg/d , n = 24 ) ; the planned duration of the trial was 5 years . Carotid IMT and vascular lumen diameter were determined by ultrasonography for all patients at baseline and at 1 , 3 , and 5 years . Furthermore , nitrite/nitrate , asymmetrical dimethyl-l-arginine , and isoprostane levels were measured . RESULTS In our conditions , IMT of the right and left common carotid arteries was similar at baseline in both groups ( P = NS ) . Intima-media thickness measurements until 5 years revealed a significant reduction in the zofenopril group but not in the enalapril group ( P < .05 vs enalapril-treated group ) . This effect was coupled with a favorable nitric oxide/oxidative stress profile in the zofenopril group . CONCLUSIONS Long-term treatment with the sulfhydryl ACE inhibitor zofenopril besides its blood pressure-lowering effects may slow the progression of IMT of the carotid artery in newly diagnosed mildly hypertensive patients 1 This study in normotensive subjects compared the duration and consistency of action of amlodipine ( 5 mg ) and nifedipine GITS ( 60 mg ) by assessment of the attenuation of pressor responses to noradrenaline and angiotensin II . 2 Both drugs significantly attenuated pressor responses to both vasoconstrictors at 6 and 24 h post-dose with rightward shifts of up to 2.3-fold in the dose-response curves . 3 There was significantly less pharmacokinetic variability with amlodipine : for example , intra-subject variability was 33 % with amlodipine and 59 % with nifedipine GITS . 4 There were no significant differences in the pressor dose ratios up to 48 h post-dose with amlodipine whereas there was a significant and progressive reduction in the pressor dose ratios with nifedipine . 5 These results suggest that both drugs are broadly comparable as once daily treatments but amlodipine displayed less intra- and inter-subject variability and provided a significantly more sustained effect with a reserve of pharmacological activity up to 48 h post-dose Information on indices of coronary heart disease ( CHD ) and myocardial infa rct ion ( MI ) ( angina pectoris by Rose Question naire , MI by Rose Question naire , history , and electrocardiogram ) was obtained in the Hypertension Detection and Follow-Up Program ( U.S. National Institutes of Health ) at baseline , Year 2 , and Year 5 of follow-up . The presence of any of these findings at baseline markedly increased all-cause mortality during the 5 years of observation . In individuals with negative findings at baseline , the 5-year incidence of MI and angina pectoris by these indices was less in the Stepped Care than Referred Care cohort . These results are compatible with the conclusion that antihypertensive therapy reduces the incidence of symptomatic CHD Objective : Our aim was to compare the effect of lacidipine and chlorthalidone on cardiovascular outcome as a primary parameter and blood pressure as a secondary in elderly patients with isolated systolic hypertension in a prospect i ve study with an open design . Methods : 1882 males and females out patients ≥60 years were r and omly assigned to the administration of  chlorthalidone 12.5 mg o.d . or lacidipine 4 mg o.d . Patients were recruited if sitting systolic blood pressure was ≥160 mmHg with a diastolic blood pressure equal or lower than 95 mmHg .  Primary endpoint was a composite of cardiovascular and cerebrovascular events . Results : At r and omization mean systolic blood pressure was 178.1 mmHg in the lacidipine and 178.2 mmHg in the chlorthalidone group , the corresponding mean diastolic values being 86.9 and 86.8 mmHg . In both lacidipine and chlorthalidone groups treatment caused a significant ( p < 0.001 ) and marked systolic blood pressure reduction which was maintained throughout the treatment period with a significant ( p < 0.001 ) and steady although less marked reduction in diastolic blood pressure as well . At the end of treatment period ( median 32 months ) , the reduction was 36.8/8.1 mmHg ( systolic/diastolic ) in the chlorthalidone and 38.4/7.9 mmHg in the lacidipine group , the final on treatment blood pressures being 142.0/79.2 and 143.2/79.5 mmHg , respectively . Treatments were similarly effective in males and females and in age groups between 60 and 69 years ( n = 763 ) , 70 and 79 years ( n = 744 ) and ≥80 years ( n = 375 ) . Similar reductions were obtained in a subgroup of patients ( n = 209 ) followed in double-blind fashion for 1 year . The overall incidence of the primary endpoints was 9.3 % with no significant between-group difference . Total mortality was also similar between groups . Conclusions : In elderly patients with isolated systolic hypertension , administration of lacidipine or chlorthalidone markedly reduced systolic blood pressure with no difference in the incidence of cardiovascular events and total mortality BACKGROUND Differences between the antihypertensive responses to drug therapy measured by office blood pressure ( OBP ) and ambulatory blood pressure monitoring ( ABPM ) techniques have been noted but rarely analyzed . We studied whether the OBP and 24-h ABPM responses to hydrochlorothiazide differ and , if so , the relevance of these differences . METHODS The  OBP and ABPM responses to hydrochlorothiazide ( 25 mg/d , for 4 weeks ) were measured in 228 subjects with essential hypertension , and mean responses were compared between methods using the Student paired t test . To assess variation in the agreement between OBP and ABPM responses among subjects , the limits of agreement were calculated as the mean difference between OBP and ABPM responses + /-2 st 
    Output:
    
In conclusion , CTDN is superior to HCTZ in preventing cardiovascular events .
This can not be attributed entirely to the lesser effect of HCTZ on office systolic blood pressure but may be attributed to the pleomorphic effects of alternative medications or to the short duration of action of HCTZ