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 .
Double‐Blind Comparison of Antihypertensive Treatment with Ramipril and Piretanide, Given Alone or in Combination
Summary : In a double-blind , r and omized , multicenter trial , we compared the efficacy and safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the respective component monotherapies in hypertensive patients [ supine diastolic blood pressure ( DBP ) 100–114 mm Hg ] . After a single-blind run-in period on placebo , 611 patients were r and omized to ramipril ( n = 209 ) , piretanide ( n = 201 ) , or the combination therapy  ( n = 201 ) . At r and omization , the three groups had the same characteristics ( 51 % men , age 55 ± 10 years , BP 165 ± 18/104 ± 6 mm Hg ) . At 4 weeks , BP decreased more with combined therapy than with monotherapy . As compared with piretanide monotherapy , the gain in the antihypertensive effect in the supine position averaged 2.1 mm Hg [ 90 % confidence interval ( CI ) - 0.8–5.0 mm Hg ; p = 0.07 ] systolic BP ( SBP ) and 1.9 mm Hg ( CI 0.3–3.5 mm Hg , p = 0.02 ) DBP and , as compared with ramipril monotherapy , these differences were 4.2 mm Hg ( CI 1.3–7.0 mm Hg , p = 0.008 ) and 2.0 mm Hg ( CI 0.5–3.6 mm Hg , p = 0.009 ) . The incidence of adverse events ( AE ) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously reported polyuria and serum uric acid concentration . Polyuria was reported more frequently ( p < 0.001 ) with piretanide therapy ( n = 23 ) and combined therapy ( n = 19 ) than with ramipril therapy ( n = 1 ) . Similarly , serum uric acid increased more ( p < 0.001 ) in the piretanide group ( + 24 μM ) and in the group receiving combined therapy ( + 18 μM ) as compared with the ramipril group ( + 0 μM ) . However , serum uric acid levels and the incidence of polyuria were similar with piretanide and combined therapy . As compared with the respective monotherapies , combined treatment with ramipril and piretanide produced an additional BP-lowering effect and did not lead to more frequent side effects
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 .