The effect was similar to that obtained when thiazides are used as a single agent .
Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are added as a first-line drug .
This means that the BP lowering effect of thiazides is additive .
Loop diuretics appear to have a similar blood pressure lowering effect as thiazides at 1 times the recommended starting dose .
Because of the short duration of the trials and lack of reporting of adverse events , this review does not provide a good estimate of the incidence of adverse effects of diuretics given as a second-line drug
BACKGROUND Diuretics are widely prescribed for hypertension not only as a first-line drug but also as a second-line drug .
Therefore , it is essential to determine the effects of diuretics on blood pressure ( BP ) , heart rate and withdrawals due to adverse effects ( WDAEs ) when given as a second-line drug .
Comparison of valsartan/hydrochlorothiazide combination therapy at doses up to 320/25 mg versus monotherapy: a double-blind, placebo-controlled study followed by long-term combination therapy in hypertensive adults.
BACKGROUND One third of patients treated for hypertension attain adequate blood pressure ( BP ) control , and multidrug regimens are often required . Given the lifelong nature of hypertension , there is a need to evaluate the long-term efficacy and tolerability of higher doses of combination anti-hypertensive therapies . OBJECTIVE This study investigated the efficacy and tolerability of valsartan ( VAL ) or hydrochlorothiazide (HCTZ)-monotherapy and higher-dose combinations in patients with essential hypertension . METHODS The first part of this study was an 8-week , multicenter , r and omized , double-blind , placebo controlled , parallel-group trial . Patients with essential hypertension ( mean sitting diastolic BP [ MSDBP ] , > or = 95 mm Hg and < 110 mm Hg ) were r and omized to 1 of 8 treatment groups : VAL 160 or 320 mg ; HCTZ 12.5 or 25 mg ; VAL/HCTZ 160/12.5 , 320/12.5 , or 320/25 mg ; or placebo .  Mean changes in MSDBP and mean sitting systolic BP ( MSSBP ) were analyzed at the 8-week core study end point . VAL/HCTZ 320/12.5 and 320/25 mg were further investigated in a 54-week , open-label extension . Response was defined as MSDBP < 90 mm Hg or a > or = 10 mm Hg decrease compared to baseline . Control was defined as MSDBP < 90 mm Hg compared with baseline . Tolerability was assessed by monitoring adverse events at r and omization and all subsequent study visits and regular evaluation of hematology and blood chemistry . RESULTS A total of 1346 patients were r and omized into the 8-week core study ( 734 men , 612 women ; 924 white , 291 black , 23 Asian , 108 other ; mean age , 52.7 years ; mean weight , 92.6 kg ) . All active treatments were associated with significantly reduced MSSBP and MSDBP during the core 8-week study , with each monotherapy significantly contributing to the overall effect of combination therapy ( VAL and HCTZ , P < 0.001 ) . Each combination was associated with significantly greater reductions in MSSBP and MSDBP compared with the monotherapies and placebo ( all , P < 0.001 ) . The mean reduction in MSSBP/MSDBP with VAL/HCTZ 320/25 mg was 24.7/16.6 mm Hg , compared with 5.9/7.0 mm Hg with placebo . The reduction in MSSBP was significantly greater with VAL/HCTZ 320/25 mg compared with VAL/HCTZ 160/12.5 mg ( P < 0.002 ) . Rates of response and BP control were significantly higher in the groups that received combination treatment compared with those that received monotherapy . The incidence of hypokalemia was lower with VAL/HCTZ combinations ( 1.8%-6.1 % ) than with HCTZ monotherapies ( 7.1%-13.3 % ) . The majority of adverse events in the core study were of mild to moderate severity . The efficacy and tolerability of VAL/HCTZ combinations were maintained during the extension ( 797 patients ) . CONCLUSIONS In this study population , combination therapies with VAL/HCTZ were associated with significantly greater BP reductions compared with either monotherapy , were well tolerated , and were associated with less hypokalemia than HCTZ alone
The effect was similar to that obtained when thiazides are used as a single agent .
Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are added as a first-line drug .
This means that the BP lowering effect of thiazides is additive .
Loop diuretics appear to have a similar blood pressure lowering effect as thiazides at 1 times the recommended starting dose .
Because of the short duration of the trials and lack of reporting of adverse events , this review does not provide a good estimate of the incidence of adverse effects of diuretics given as a second-line drug
BACKGROUND Diuretics are widely prescribed for hypertension not only as a first-line drug but also as a second-line drug .
Therefore , it is essential to determine the effects of diuretics on blood pressure ( BP ) , heart rate and withdrawals due to adverse effects ( WDAEs ) when given as a second-line drug .