EAL

HESI: Congestive Heart Failure Population (2014)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether the administration of acetylsalicylic acid had adverse effects on renal functional parameters in patients with moderate chronic congestive heart failure with and without stimulation of the renin system induced by low sodium diet.

Inclusion Criteria:

Patients with stable CHF
New York Heart Association criteria (NYHA) class II to III
Normal renal function
Reduced left ventricular ejection fraction (LVEF) less than 45%
Elevated pulmonary capillary wedge pressure greater than 15mmHg
Reduced cardiac index less than 2.5 L per minute per m².

Exclusion Criteria:

Serum creatinine greater than 1.3mg per dL
History of acetylsalicylic acid intolerance
Unstable angina or myocardial infarction within the last six weeks.

Description of Study Protocol:

Recruitment: Not reported
Design: Parallel, RCT
Blinding used: Double-blind.

Intervention

Low and normal-sodium diet

Low-sodium diet consisted of 312.8mg per day of sodium diet (intervention)
Normal-sodium diet consisted of 3,128mg per day of sodium (control).
Patients were either on a low-sodium diet or normal diet for four days.

Acetylsalicylic acid or placebo

2x500mg acetylsalicylic acid or two capsules of placebo on Day Five
3x500mg acetylsalicylic acid or three capsules of placebo after Day Five
On Day Five, patients received either acetylsalicylic acid or placebo.

Groups

Group One: Low-sodium diet and placebo
Group Two: Low-sodium diet and acetylsalicylic acid
Group Three: Normal-sodium diet and placebo
Group Four: Normal-sodium diet and acetylsalicylic acid.

Statistical Analysis

Chi-Square test for categorical variables and one-way analysis of variance for continuous variables when comparing the baseline characteristics
Wilcoxon test to analyze the effects of a low-sodium vs. a normal diet
Analysis of variance for repeated measurements to analyze the changes in the continuous data between Days Five and Eight within the four groups. When F-value was significant, Wilcoxon test was used.
Two-tailed P-value of less than 0.5 was considered statistically significant.

Data Collection Summary:

Timing of Measurements

24-hour urine was collected to measure endogenous creatinine clearance and electrolyte excretion from Day Four to Five
On Day Five, serum electrolytes, creatinine and plasma levels of renin, aldosterone and atrial natriuretic peptide were measured
Urine specimens for measurement of creatinine clearance and electrolyte and blood samples were collected again on Days Seven and Eight.

Dependent Variables

Glomerular filtration rate: Estimated by endogenous creatinine clearance, calculated according to the "conventional clearance formula."
Serum and urine concentration of creatinine: Measured by an automatic analyzer
Renal sodium excretion: Serum and urinary concentrations of sodium determined by flame photometry
Plasma renin concentration, aldosterone and atrial natriuretic peptide: Measured by radioimmunoassay
Urinary prostaglandin E₂: Measured by radioimmunoassay.

Independent Variables

Low-sodium diet
Normal-sodium diet
Acetylsalicylic acid.

Description of Actual Data Sample:

Initial N: 40; 20 patients in the low-sodium diet and 20 patients in the normal sodium diet during pre-treatment (first intervention with diet only). Sample size for each of the four groups was not reported.
Attrition (final N): Same as above
Age: 60.8±2.2 years
Ethnicity: Not reported.

Other Relevant Demographics

All vasodilator drugs were discontinued during the studied period
Diuretic therapy was discontinued three days prior to randomization
Digitalis treatment was maintained unchanged throughout the study
Baseline characteristics including etiology, duration and severity of congestive heart failure, previous treatment, sex, age, weight, cardiothoracic ratio, mean arterial blood pressure and serum and urinary variables did not significantly differ between groups.

Anthropometrics
Not reported.

Location
Würzburg, Federal Republic of Germany.

Summary of Results:

Key Findings

Low-sodium diet (LSD) was associated with significant reduction of glomerular filtration rate in placebo (estimated from the figure, from 90mcmol to 70mcmol per minute; P<0.007) and acetylsalicylic (estimated from the figure, from 105mcmol to 79mcmol per minute; P<0.03) groups at the end of the study
Renal sodium excretion was significantly reduced with low-sodium diet compared to normal sodium diet; 18.8±3.9mcmol; 74.0±8.0mcmol per minute, respectively; P=0.0001
LSD compared to normal sodium diet resulted in a significant increase of urinary prostaglandin E₂(360±56pg and 196±51pg per ml, respectively; P=0.01)
Acetylsalicylic acid reduced significantly the renal sodium excretion rate by 29% (P<0.04) in the group of patients receiving normal sodium diet, but not in the Low-Sodium Diet Group (NS)
Acetylsalicylic acid reduced the elevated urinary prostaglandin E2 in patients on the LSD (from 344±75pg to 179±44pg per ml) and normal sodium diet (from 172±59pg to 109±33pg per ml); both P=0.02.

Other Findings

The low-sodium diet compared to normal sodium diet increased plasma renin significantly (15.2±3.8ng and 3.1±0.5ng per Al per ml per hour; P<0.0001) and aldosterone concentration (415±42pg and 234±26pg per ml; P<0.0006, respectively)
Potassium excretion rate was increased with the low-sodium diet 58.7±4.5mcmol per minute, compared to normal sodium diet 42.8±3.0mcmol per minute (P<0.009).

Author Conclusion:

Severe sodium depletion has adverse effects on kidney function in patients with heart failure due to a reduction in the glomerular filtration rate
Administration of acetylsalicylic acid in doses that reduce the synthesis of renal prostaglandin E₂ significantly reduces renal sodium excretion.

Funding Source:

Government:	Deutsche Forschungsgemeinschaft
University/Hospital:	Medizinische Universitatsklinil, Wurzburg, Germany

Reviewer Comments:

Baseline characteristics were only mentioned without the measurements
The severe low-sodium diet is not realistic, therefore the results may not be reliable for clinical guidance.

What was the baseline nutrient status (i.e., sodium)? For example the baseline sodium status can be used as an inclusion criterion for entry into study, and recorded in the report of the trial.	No
What was the target sodium intake in the intervention and comparison groups?	Low-Sodium Diet Group: 312.8mg/day Normal-Sodium Diet: 3,128mg/day
Was the difference in sodium status (i.e., change in urinary sodium excretion) measured between groups? If so, please specify.	After 4-days on diet: Low-sodium diet (LSD): Renal sodium excretion, 18.8±3.9mcmol/minute Normal sodium diet (NSD): 74±0.8mcmol/minute After treatment with acetylsalicylic acid or placebo: LSD: No change After treatment with acetylsalicylic acid: NSD: Estimated from the figure -52mcmol/minute
Was the status of other nutrient (e.g., potassium and calcium) measured in order to ensure that the test nutrient (i.e., sodium) is the only nutrition-related, limiting factor in the response? If yes, please specify.	Low-sodium diet: Renal potassium excretion, 58.7±4.5mcmol/minute Normal sodium diet: Renal potassium excretion, 42.8±3mcmol/minute

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	3.	Were study groups comparable?	???
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
	4.	Was method of handling withdrawals described?	???
4.	Was method of handling withdrawals described?		???
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	???
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	5.	Was blinding used to prevent introduction of bias?	Yes
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
	6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?	Yes
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	???
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
	7.	Were outcomes clearly defined and the measurements valid and reliable?	Yes
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	???
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	???
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
	8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
	9.	Are conclusions supported by results with biases and limitations taken into consideration?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	No
	9.2.	Are biases and study limitations identified and discussed?	No
	10.	Is bias due to study's funding or sponsorship unlikely?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes