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. 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 (1946-February 2012), EMBASE (1974-February 2012), CENTRAL (issue 2, 2012) 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 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 systolic/diastolic blood pressure 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. The 2012 updated search resulted in no additional new trials meeting the minimum inclusion criteria. Authors' conclusions Based on the limited number of published RCTs, the systolic/diastolic blood pressure 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 are 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 with loop diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.