Diuretics effective in lowering blood pressure when given as a second drug

Chen JMH, Heran BS, Wright JM

Published Online:

October 7, 2009

Diuretics are a good first-line treatment for high blood pressure (BP). Diuretics include loop diuretics and thiazides. We asked how much do diuretics reduce BP when used as the second drug to treat hypertension. We performed a search of the available scientific literature to find all trial evidence to assess this question. Fifty-six trials were found. Fifty-three trials involved thiazide diuretics (92% with the drug hydrochlorothiazide) and included a total of 15310 participants. Adding a thiazide to another anti-hypertensive drug further reduces the BP by an additional 6/3 mmHg when given at the starting dose and reduces BP by 8/4 mmHg at 2 times the starting dose. This is approximately the same effect as when the drugs are used alone. A good estimate of the harms associated with diuretics cannot be estimated in this review because of the lack of reporting and the short duration of the trials.

Abstract (click to read)

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.

Objectives:

To quantify the additional reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) of diuretic therapy as a second-line drug in patients with primary hypertension

Search strategy:

CENTRAL (The Cochrane Library 2008, Issue 2), MEDLINE (1966-July 2008), EMBASE (1988-July 2008) and bibliographic citations of articles and reviews were searched.

Selection criteria:

Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of a diuretic in combination therapy with another class of anti-hypertensive drugs compared with the respective monotherapy (without a diuretic) for a duration of 3 to 12 weeks in patients with primary hypertension.

Data collection and analysis:

Two review authors independently extracted the data and assessed trial quality.

Main results:

Fifty-three double-blind RCTs evaluating a thiazide in 15129 hypertensive patients (baseline BP of 156/101 mmHg) were included. Hydrochlorothiazide was the thiazide used in 49/53 (92%) of the included studies. The additional BP reduction caused by the thiazide as a second drug was estimated by comparing the difference in BP reduction between the combination and monotherapy groups. Thiazides as a second-line drug reduced BP by 6/3 and 8/4 mmHg at doses of 1 and 2 times the manufacturer's recommended starting dose respectively. The BP lowering effect was dose related. The effect was similar to that obtained when thiazides are used as a single agent. Only 3 double-blind RCTs evaluating loop diuretics were identified. These RCTs showed a BP lowering effect of a starting dose of about 6/3 mmHg.

Authors' conclusions:

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.

This record should be cited as:

Chen JMH, Heran BS, Wright JM. Blood pressure lowering efficacy of diuretics as second-line therapy for primary hypertension. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD007187. DOI: 10.1002/14651858.CD007187.pub2

Assessed as up to date:

January 1, 2009

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Primary Review Group:

Hypertension Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are diuretics as second-line therapy for primary hypertension?

Bottom line:

Thiazides as a second-line drug reduced blood pressure (BP) by 6/3 and 8/4mmHg at doses of 1 and 2 times the manufacturer’s recommended starting dose, respectively. Although the dose of hydrochlorothiazide (HCTZ) was studied over a wide range (5mg/ day to 45mg/day), a majority of the trials evaluated doses of 12.5mg/day and 25mg/day. The BP lowering effect was dose related. The effect seen was similar to that obtained when thiazides are used as a single agent. HCTZ was the thiazide used in 49 of 53 (92%) of the included studies. Only 3 double-blind randomised controlled trials (RCTs) evaluating loop diuretics were identified. These RCTs showed a BP lowering effect of about 6/3mmHg for a starting dose (piretanide 3mg/day and 6mg/day; frusemide 40mg/day).

Caveat:

Due to the short duration of the trials (3–12 weeks) 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 blood pressure lowering drug treatment.

Context:

Even with individualised monotherapy, BP targets are not likely to be achieved with the first drug used, even when titrated to high doses. Diuretics (thiazides and loop diuretics) are widely prescribed for hypertension, not only as a first-line drug treatment but also as a second-line treatment.

Cochrane Systematic Review:

Chen JMH et al. Blood pressure lowering efficacy of diuretics as second-line therapy for primary hypertension. Cochrane Reviews 2009, Issue 4. Article No. CD007187. DOI: 10.1002/14651858. CD007187.pub2. This review contains 53 studies involving 15,129 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Heart & circulation > Hypertension > Treatment: pharmacological

Kidney disease > Hypertension > Treatment: pharmacological

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Diuretics effective in lowering blood pressure when given as a second drug

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