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 .
Controlled Multicenter Study of the Antihypertensive Effects of Lisinopril, Hydrochlorothiazide, and Lisinopril plus Hydrochlorothiazide in the Treatment of 394 Patients with Mild to Moderate Essential Hypertension
Lisinopril ( LIS ) is a lysine analog of enalaprilat , the active metabolite of enalapril , an angiotensin-converting enzyme inhibitor ( ACEI ) . Unlike enalapril , the precursor of enalaprilat , LIS is not a prodrug but has equal ACEI efficacy and potency and a slightly longer duration of action after oral administration . Short-term ( 12 weeks ) and long-term ( 24 weeks ) blood pressure control has been studied with LIS , hydrochlorothiazide ( HCTZ ) , and LIS + HCTZ when given once a day . Drug treatment had three phases : ( i ) 2–4 weeks of single-blind placebo washout ; ( ii ) 12 weeks of double-blind comparison therapy with LIS 20 , 40 . and 80 mg vs. HCTZ 12.5 , 25 , and 50 mg , vs. LIS + HCTZ 20 + 12.5 , 40 + 25 . and 80 + 50 mg ; ( iii ) 13–24 weeks single-blind LIS vs. LIS + HCTZ . Starting double-blind therapy at the lowest dose , all three groups doubled the dose at weeks 4 and 8 if BP was not controlled with sitting diastolic BP ( SDBP ) < 90 mm Hg . At the end of 12 weeks of double-blind therapy , uncontrolled HCTZ-only and LIS-only treatment groups were advanced to combination LIS + HCTZ therapy but uncontrolled LIS + HCTZ patients were dropped . Mean BP reductions ( systolic/diastolic , mm Hg ) for all three groups after 12 weeks of double-blind comparison therapy were : ( i ) LIS ( n = 162 ) , – 16.6/-12.5 ; ( ii ) HCTZ ( n = 155 ) , – 10.4/-6.8 : ( iii ) LIS + HCTZ ( n = 74 ) . −23.9/- 18.2 with p < 0.01 for all groups compared to baseline . Significant ( p < 0.01 ) decreases in SDBP with all therapies were seen regardless of race , but nonblack patients responded better than black patients to LIS alone . During the second treatment period ( weeks 13–24 ) , 89 % of patients ( 177/199 ) at week 24 had SDBP ≤ 85 mm Hg or ≥ 10 mm Hg SDBP reduction . By 24 weeks , 82 % ( 72/88 ) of LIS-treated patients maintained this BP control , whereas 84 % ( 48/57 ) of LIS + HCTZ-treated patients and 67 % ( 36/54 ) of HCTZ-treated patients sustained identical BP control . By 22 weeks , 68 % ( 81/119 ) of patients maintained BP control on LIS monotherapy . With ≤ 20 mg LIS therapy , 41 % ( 33/81 ) achieved long-term BP control , whereas 65 % and 72 % of these patients responded to ≤ 40 mg and ≥ 80 mg LIS doses , respectively . Serious adverse clinical effects in all groups were rare ( < s3 % ) during short-term and long-term therapy . In conclusion , LIS therapy alone ( 20–80 mg q.d . ) is more efficacious than HCTZ therapy alone ( 12.5–50 mg q.d . ) . LIS + HCTZ [ ( 20 + 12.5)-(80 + 50 ) mg q.d . ] is more efficacious than either LIS therapy alone ( 20–80 mg q.d . ) or HCTZ therapy alone ( 12.5–50 mg q.d . ) . Lisinopril and LIS + HCTZ  are effective and well tolerated antihypertensive agents in both short- and long-term therapy
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 .