Blood pressure lowering efficacy of loop diuretics for primary hypertension.
BACKGROUND
Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop diuretics are indicated and used as antihypertensive drugs but a systematic review of their blood pressure lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial evidence has not been conducted.


OBJECTIVE
To determine the dose related decrease in systolic and/or diastolic blood pressure as well as adverse events leading to patient withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to loop diuretics versus placebo control in the treatment of patients with primary hypertension.


METHODS
Medline (Jan.1966-March-2009), EMBASE (Jan.1988-March-2009), CENTRAL (issue 1, 2009) and bibliographic citations were searched.


METHODS
Double blind randomized placebo controlled trials of at least 3 weeks duration comparing loop diuretic with a placebo or no treatment in patients with primary hypertension defined as BP >140/90 mmHg at baseline were included.


METHODS
Two authors independently assessed the risk of bias and extracted data. Weighted mean difference and a fixed effects model were used to combine continuous outcome data. The drop outs due to adverse effects was analysed using relative risk ratio.


RESULTS
Nine trials evaluated the dose-related blood pressure lowering efficacy of five drugs within the loop diuretics class (furosemide 40 to 60mg, cicletanine 100 to 150 mg, piretanide 3 to 6 mg, indacrinone enantiomer -2.5 to -10.0/+80 mg and etozolin 200 mg) in 460 patients with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of SBP/DBP lowering efficacy of loop diuretics was -7.9 (-10.5, -5.4) mmHg/ -4.4 (-5.6, -2.8) mmHg . Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.


CONCLUSIONS
Based on the limited number of published RCTs, the SBP/DBP lowering effect of loop diuretics is modest -8/-4 mmHg and is likely an overestimate due to the high risk of bias in the included studies. There is no clinically meaningful BP lowering differences between different drugs within the loop diuretic class. The dose ranging effects of loop diuretics could not be evaluated.The review did not provide a good estimate of the incidence of harms associated because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
Musini
Vijaya M
VM
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Science Mall, Vancouver, BC, Canada, V6T 1Z3.
Wright
James M
JM
Bassett
Ken
K
Jauca
Ciprian D
CD
D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects
D000959:Antihypertensive Agents; D049994:Sodium Potassium Chloride Symporter Inhibitors