Blood pressure lowering efficacy of loop diuretics for primary hypertension
Abstract
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.
Objectives
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.
Search methods
Medline (Jan.1966‐March‐2009), EMBASE (Jan.1988‐March‐2009), CENTRAL (issue 1, 2009) and bibliographic citations were searched.
Selection criteria
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.
Data collection and analysis
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.
Main 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.
Authors' 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.
PICOs
Plain language summary
Loop diuretics cause modest blood pressure lowering
Loop diuretics are more commonly used to reduce water retention, but are also indicated to lower elevated blood pressure. We asked how much this class of drugs lowers blood pressure and whether there is a difference between individual drugs within the class. The available scientific literature was searched to find all the trials that had assessed this question. We found only 9 trials studying the blood pressure lowering ability of 5 different loop diuretics (furosemide, cicletanine, piretanide, indacrinone and etozolin) in 460 participants. The blood pressure lowering effect was modest; lowering systolic pressure by 8 mmHg and the diastolic pressure by 4 mmHg. No loop diuretic drug appears to be any better or worse than others in terms of blood pressure lowering ability. Due to lack of reporting and the short duration of these trials, this review could not provide an estimate of the harms associated with this class of drugs.
