Journal of Cardiovascular Nursing
Vol. 29, No. 3, pp 205Y206 x Copyright B 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Cochrane Nursing Care Corner Blood PressureYLowering Efficacy of Loop Diuretics for Primary Hypertension Karolina Lisy, BSc (Hons), PhD
KEY WORDS:
blood pressure, hypertension, loop diuretics
Review Questions h What is the dose-dependent
effect on systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) of loop diuretics compared with placebo in the treatment of patients with primary hypertension? h What are the adverse events associated with loop diuretic treatment?
Relevance to Nursing Primary hypertension is associated with an increased risk for many serious health events, including myocardial infarction, heart failure, stroke, aortic aneurysm, and periphKarolina Lisy, BSc (Hons), PhD Research Fellow, Communication Science, The Joanna Briggs Institute, The University of Adelaide, Australia. Karolina Lisy, BSc (Hons), PhD, is a member of the Cochrane Nursing Care Field (CNCF). This is a summary of a Cochrane Review. The full citation and the names of the researchers who conducted the review are listed in the Reference section below. The author has no funding or conflicts of interest to disclose.
Correspondence Karolina Lisy, BSc (Hons), PhD, Communication Science, The Joanna Briggs Institute, The University of Adelaide, South Australia, 5005 Australia ([email protected]). DOI: 10.1097/JCN.0b013e318296de8b
eral arterial disease. People with chronic hypertension have a reduced life expectancy, and drugs that reduce blood pressure are often prescribed to reduce morbidity and mortality in patients with hypertension. Loop diuretics are the most powerful class of diuretic drugs and act on the ascending loop of Henle in the kidney. The effect of loop diuretics on blood pressure has not been previously examined in a systematic review. For nurses to better provide care, advice, and support to people who may require or who already are receiving blood pressure medication, it is important that nurses be apprised of the latest evidence regarding the use of loop diuretics for the treatment of primary hypertension.
Study Characteristics A total of 9 studies were included in the review,1 encompassing 460 participants. All of the included studies were double-blind placebocontrolled trials, with random allocation to treatment or control groups. Patients of any age or gender were included, provided that their baseline SBP was at least
140 mm Hg and/or their baseline DBP was at least 90 mm Hg. Patients with renal insufficiency and elevated serum creatinine levels were excluded from the analysis; however, patients with any other comorbidities were included. The intervention investigated was monotherapy with various doses of drugs belonging to the loop diuretic class. The included studies used furosemide, piretanide, indacrinone, etozolin, and cicletanine for treatment, and each drug was compared with placebo. Of the total number of participants, 242 and 198 patients were allocated to the treatment and control arms of the 9 trials, respectively. Treatment periods ranged from 4 weeks to 180 days, with a mean duration of 8.8 weeks and with a minimum follow-up time of 3 weeks. The primary outcomes measured were changes in SBP and DBP. The secondary outcomes of interest were the number of patients who withdrew from the trials because of adverse events and also biochemical analysis to indicate changes in serum levels of potassium, uric acid, creatinine, cholesterol, triglcyerides, and blood glucose after treatment. Meta-analysis was undertaken where possible. 205
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
206 Journal of Cardiovascular Nursing x May/June 2014 There was a perceived high risk for bias because of inadequate description of blinding in 4 studies and incomplete data reporting in 4 studies; 4 studies had high risk for other bias that was not specified. Publication bias was also detected and was thought to impact significantly on the results of the review. The review described the effects of the drugs on SBP and DBP separately. The results were as follows: h Sixty milligrams of furosemide signif-
h
h
h
h
icantly reduced SBP (j10 mm Hg; 95% confidence interval [CI], j15.8 to j4.2 mm Hg; 1 trial), whereas 40 mg did not (two trials). One hundred milligrams of cicletanine did not significantly reduce SBP (one trial), but 150 mg did (j9.1 mm Hg; 95% CI, j15.5 to j2.7 mm Hg; 1 trial). Piretanide at either 3 mg or 6 mg did not significantly affect SBP (1 and 2 trials, respectively). Only 1 dose of the drug etozolin was included, with 200 mg significantly reducing SBP by j14.30 mm Hg (95% CI, j23.05 to j5.55 mm Hg; 1 trial). Different ratios of indacrinone enantiomers had varying effects, with j2.5 mg/+80 mg and j5.0 mg/+80 mg not causing a significant change in SBP (one trial) and j10.0 mg/+80 mg resulting
in a significant reduction in SBP (j19.1; 95% CI, j35.9 to j2.25 mm Hg; 1 trial). h Combined, the various loop diuretics from all 9 trials lowered SBP by 7.9 mm Hg (95% CI, j10.5 to j5.4 mm Hg). h Analysis of the effect on DBP of the described doses of each drug resulted in only 150 mg of cicletanine producing a significant decrease in DBP (j11.3; 95% CI, j15.3 to j7.3 mm Hg; 1 trial). Taken together, the results from all 9 included trials showed a reduction in DBP of 4.4 mm Hg (95% CI, j5.9 to j2.8 mm Hg). Six of the 9 included studies reported patient withdrawals due to adverse effects; however, these were not deemed to be statistically significant. The nature of the adverse events was not reported. Two of the studies investigated various biochemical effects of loop diuretic treatment, with none reaching statistical significance. Overall, this review highlighted the paucity of available data on the efficacy of loop diuretics in the treatment of primary hypertension. Because of the limited evidence available, the authors were not able to generate dose-response curves for the various drugs for the reduction of SBP and DBP. It was also not possible to determine the relative
effects of each drug on blood pressure because there were no trials that compared 1 drug with another. The lack of available evidence and the publication bias detected for the included studies demonstrate a need for the release of unpublished trial data.
Best Practice Recommendations The findings of the review were not sufficient to enable recommendations for practice. On the basis of the included studies, the effect of loop diuretics on SBP and DBP was modest, with an overall decrease of 8/4 mm Hg. Because there was a high risk for publication bias, the effect may have been overestimated. Because of a lack of reporting of adverse effects in the source studies, the review was not able to include information regarding the incidence and nature of adverse effects when using loop diuretics for the treatment of primary hypertension.
REFERENCE 1. Musini VM, Rezapour P, Wright JM, Bassett K, Jauca CD. Blood pressure lowering efficacy of loop diuretics for primary hypertension. Cochrane Database Syst Rev. 2012;(8):CD003825. doi:10.1002/14651858.CD003825. pub3.
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Vol. 29, No. 3, pp 205Y206 x Copyright B 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Cochrane Nursing Care Corner Blood PressureYLowering Efficacy of Loop Diuretics for Primary Hypertension Karolina Lisy, BSc (Hons), PhD
KEY WORDS:
blood pressure, hypertension, loop diuretics
Review Questions h What is the dose-dependent
effect on systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) of loop diuretics compared with placebo in the treatment of patients with primary hypertension? h What are the adverse events associated with loop diuretic treatment?
Relevance to Nursing Primary hypertension is associated with an increased risk for many serious health events, including myocardial infarction, heart failure, stroke, aortic aneurysm, and periphKarolina Lisy, BSc (Hons), PhD Research Fellow, Communication Science, The Joanna Briggs Institute, The University of Adelaide, Australia. Karolina Lisy, BSc (Hons), PhD, is a member of the Cochrane Nursing Care Field (CNCF). This is a summary of a Cochrane Review. The full citation and the names of the researchers who conducted the review are listed in the Reference section below. The author has no funding or conflicts of interest to disclose.
Correspondence Karolina Lisy, BSc (Hons), PhD, Communication Science, The Joanna Briggs Institute, The University of Adelaide, South Australia, 5005 Australia ([email protected]). DOI: 10.1097/JCN.0b013e318296de8b
eral arterial disease. People with chronic hypertension have a reduced life expectancy, and drugs that reduce blood pressure are often prescribed to reduce morbidity and mortality in patients with hypertension. Loop diuretics are the most powerful class of diuretic drugs and act on the ascending loop of Henle in the kidney. The effect of loop diuretics on blood pressure has not been previously examined in a systematic review. For nurses to better provide care, advice, and support to people who may require or who already are receiving blood pressure medication, it is important that nurses be apprised of the latest evidence regarding the use of loop diuretics for the treatment of primary hypertension.
Study Characteristics A total of 9 studies were included in the review,1 encompassing 460 participants. All of the included studies were double-blind placebocontrolled trials, with random allocation to treatment or control groups. Patients of any age or gender were included, provided that their baseline SBP was at least
140 mm Hg and/or their baseline DBP was at least 90 mm Hg. Patients with renal insufficiency and elevated serum creatinine levels were excluded from the analysis; however, patients with any other comorbidities were included. The intervention investigated was monotherapy with various doses of drugs belonging to the loop diuretic class. The included studies used furosemide, piretanide, indacrinone, etozolin, and cicletanine for treatment, and each drug was compared with placebo. Of the total number of participants, 242 and 198 patients were allocated to the treatment and control arms of the 9 trials, respectively. Treatment periods ranged from 4 weeks to 180 days, with a mean duration of 8.8 weeks and with a minimum follow-up time of 3 weeks. The primary outcomes measured were changes in SBP and DBP. The secondary outcomes of interest were the number of patients who withdrew from the trials because of adverse events and also biochemical analysis to indicate changes in serum levels of potassium, uric acid, creatinine, cholesterol, triglcyerides, and blood glucose after treatment. Meta-analysis was undertaken where possible. 205
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
206 Journal of Cardiovascular Nursing x May/June 2014 There was a perceived high risk for bias because of inadequate description of blinding in 4 studies and incomplete data reporting in 4 studies; 4 studies had high risk for other bias that was not specified. Publication bias was also detected and was thought to impact significantly on the results of the review. The review described the effects of the drugs on SBP and DBP separately. The results were as follows: h Sixty milligrams of furosemide signif-
h
h
h
h
icantly reduced SBP (j10 mm Hg; 95% confidence interval [CI], j15.8 to j4.2 mm Hg; 1 trial), whereas 40 mg did not (two trials). One hundred milligrams of cicletanine did not significantly reduce SBP (one trial), but 150 mg did (j9.1 mm Hg; 95% CI, j15.5 to j2.7 mm Hg; 1 trial). Piretanide at either 3 mg or 6 mg did not significantly affect SBP (1 and 2 trials, respectively). Only 1 dose of the drug etozolin was included, with 200 mg significantly reducing SBP by j14.30 mm Hg (95% CI, j23.05 to j5.55 mm Hg; 1 trial). Different ratios of indacrinone enantiomers had varying effects, with j2.5 mg/+80 mg and j5.0 mg/+80 mg not causing a significant change in SBP (one trial) and j10.0 mg/+80 mg resulting
in a significant reduction in SBP (j19.1; 95% CI, j35.9 to j2.25 mm Hg; 1 trial). h Combined, the various loop diuretics from all 9 trials lowered SBP by 7.9 mm Hg (95% CI, j10.5 to j5.4 mm Hg). h Analysis of the effect on DBP of the described doses of each drug resulted in only 150 mg of cicletanine producing a significant decrease in DBP (j11.3; 95% CI, j15.3 to j7.3 mm Hg; 1 trial). Taken together, the results from all 9 included trials showed a reduction in DBP of 4.4 mm Hg (95% CI, j5.9 to j2.8 mm Hg). Six of the 9 included studies reported patient withdrawals due to adverse effects; however, these were not deemed to be statistically significant. The nature of the adverse events was not reported. Two of the studies investigated various biochemical effects of loop diuretic treatment, with none reaching statistical significance. Overall, this review highlighted the paucity of available data on the efficacy of loop diuretics in the treatment of primary hypertension. Because of the limited evidence available, the authors were not able to generate dose-response curves for the various drugs for the reduction of SBP and DBP. It was also not possible to determine the relative
effects of each drug on blood pressure because there were no trials that compared 1 drug with another. The lack of available evidence and the publication bias detected for the included studies demonstrate a need for the release of unpublished trial data.
Best Practice Recommendations The findings of the review were not sufficient to enable recommendations for practice. On the basis of the included studies, the effect of loop diuretics on SBP and DBP was modest, with an overall decrease of 8/4 mm Hg. Because there was a high risk for publication bias, the effect may have been overestimated. Because of a lack of reporting of adverse effects in the source studies, the review was not able to include information regarding the incidence and nature of adverse effects when using loop diuretics for the treatment of primary hypertension.
REFERENCE 1. Musini VM, Rezapour P, Wright JM, Bassett K, Jauca CD. Blood pressure lowering efficacy of loop diuretics for primary hypertension. Cochrane Database Syst Rev. 2012;(8):CD003825. doi:10.1002/14651858.CD003825. pub3.
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
