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 .
A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide.
BACKGROUND The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design . In consultation with the Cardio-Renal Division of the Food and Drug Administration , we conducted a r and omized , double-blind , placebo-controlled , 3 x 4 factorial trial of bisoprolol , a beta 1-selective adrenergic blocking agent , and hydrochlorothiazide . METHODS A total of 512 patients with mild to moderate essential hypertension were r and omized to once-daily treatment with bisoprolol ( 0 , 2.5 , 10 , or 40 mg ) , hydrochlorothiazide ( 0 , 6.25 , or 25 mg ) , and all possible combinations .  Diastolic and systolic blood pressures were monitored during this 12-week trial . RESULTS The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied . The addition of hydrochlorothiazide ( or bisoprolol ) to therapy with bisoprolol ( or hydrochlorothiazide ) produced an incremental reduction in blood pressure . Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect . A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d . The low-dose combination of bisoprolol , 2.5 mg/d , and hydrochlorothiazide , 6.25 mg/d , reduced diastolic blood pressure to lower than 90 mm Hg in 61 % of patients and demonstrated a safety profile that compared favorably with that of placebo . CONCLUSIONS The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated . The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension
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 .