EAL

HESI: Congestive Heart Failure Population (2014)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the effects of different Na diets (120mmol or 80mmol per day) associated with different diuretic doses (more conventional or high) and different water intake restrictions (1,000ml per day vs. 2,000ml per day) on hospital readmissions for worsening HF.

Inclusion Criteria:

Compensated patients who were hospitalized within the previous 30 days for recently decompensated CHF with following characteristics:

Uncompensated CHF
NYHA functional class IV unresponsive (decrease in urine volume, constant increase in BW, impaired sx CHF) to treatment with high doses of oral furosemide up to 250mg to 500mg per day and combinations of diuretics, ACE inhibitors, digitalis, B-blockers and nitrates
Under this therapy for at least two weeks before hospitalization
Patients had to have:
- L-ventricular EF less than 35%
- Creatinine less than 2mg per dL
- BUN 60mg per dL or less
- Decreased urinary volume (less than 500ml per 24 hours)
- Low natriuresis (less than 60mmol per 24 hours).

Exclusion Criteria:

Cerebral vascular disease
Dementia
Cancer
Uncompensated diabetes
Severe haptic disease
Requiring pacemaker implantation
Alcoholic habits
Declining to take part in protocol
Unable to follow assigned treatment, did not follow treatment protocol or attend scheduled clinical visits
Did not adhere to fluid intake of 1,000ml per day or had reduction or discontinuation of prescribed treatments
Those experiencing side effects of ACE inhibitor treatment.

Description of Study Protocol:

Recruitment

Patients admitted consecutively to hospital with worsening CHF.

Design

Randomized trial with 180-day follow-up period.

Blinding Used

Physicians were blinded to protocol-judged patients to be compensated and therefore eligible for randomization into protocol. Physicians were blinded to the study-protocol-performed evaluations to verify clinical status and if worsening CHF was present (main outcome).

Intervention

Patients were randomized to either 1,000ml or 2,000ml per day fluid intake restriction
Within each fluid restriction group, different dose groups of furosemide and dietary Na intakes were assigned (eight treatment groups total):
- 120mmol Na, 250mg furosemide twice a day
- 120mmol Na, 125mg furosemide twice a day
- 80mmol Na, 250mg furosemide twice a day
- 80mmol Na, 125mg furosemide twice a day.

Statistical Analysis

Event distributions were calculated using Kaplan-Meier method and compared using log-rank analysis. Data were analyzed using two-tailed Student's T-tests.

Data Collection Summary:

Timing of Measurements

After hospital discharge, patients were controlled with clinical and lab evaluations as outpatients every week for the first 30 days, and those at 30 days post-discharge who met eligibility criteria were included in the study. After randomization (at 30 days post-discharge) and baseline clinical and lab assessments, patients were evaluated weekly for the first month, then every two weeks for the next two months, then monthly for the rest of the study.

Dependent Variables

Doses of diuretics, ACE inhibitors, digitalis, antialdosterone, beta-blockers and nitrates
Physical exam: Signs and symptoms of CHF, measurements of BW
BP and HR
Serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, glucose
Plasma aldosterone, BNP, PRA
Chest X-ray, ECG to obtain EF.

Independent Variables

Fluid restriction group (1,000ml vs. 2,000ml per day)
Na intake group (120mmol vs. 80mmol per day)
Furosemide group (250mg vs. 125mg twice a day).

Control Variables

Timing of measurements.

Description of Actual Data Sample:

Initial N: N=410 (152 male, 258 female) patients randomized into the study
Attrition (final N): At 180 days, N=370
Age: Mean, 75.5 years
Location: Palermo, Italy.

Summary of Results:

Key Findings

The group receiving 1,000ml fluid per day, 120mmol Na per day, 250mg furosemide twice a day (N=52) showed best results with a significant reduction (P<0.001) in readmissions (7.69%), and no increases in BNP, aldosterone and plasma renin activity compared with the other groups during follow-up (P<0.001). This group also showed greater daily diuresis compared with the other groups (P<0.05).

Comparison Between Baseline and After 180 Days of Follow-up

Group	Aldosterone (pg per ml)		P value	PRA (ng per ml per Hour)		P Value	BNP (pg per ml)		P Value
Group	Baseline	180 Days	P value	Baseline	180 Days	P Value	Baseline	180 Days
Group A: NSD+250mg furosemide +1,000ml fluid intake (FI)	181±133	183±156^&*	NS	3.55±2.7	3.42±2.8^&*	NS	357±145	415±155*	NS
Group B: NSD+125mg furosemide+1,000ml FI P value	179±137 NS	235±174^&* NS	NS	3.57±2.8 NS	4.22±3.8^& NS	NS	365±135 NS	555±175^&* 0.0001	0.0001
Group C: LSD+250mg furosemide+1,000ml per day FI	177±141	295±184^&	0.0001	3.71±3.2	5.73±4.1^&	0.0001	365±155	675±225^&*	0.0001
Group D: LSD+125mg furosemide+1,000mg per day P value	178±136 NS	335±238* NS	0.001	3.68±3.1 NS	5.92±5.1^& NS	0.0001	370±125 NS	745±305^*	0.0001
Group E: NSD+250mg furosemide+2,000ml	180±138	325±137&*	0.0001	3.82±3.3	5.68±4.7^&	0.024	360±165	705±245*	0.0001
Group F: NSD+125mg furosemide+2,000ml FI P value	176±149 NS	402±252&* NS	0.0001	3.75±3.4 NS	6.05±5.4^& NS	0.014	355±165 NS	795±355* NS	0.0001
Group G: LSD+250 mg furosemide+2,000 ml FI	179±151	425±316*	0.0001	3.81±3.2	6.61±6.2^&*	0.005	375±165	835±545*	0.0001
Group H- LSD+125 mg furosemide+2,000 ml FI P value	184±142 NS	475±384* NS	0.0001	3.83±3.7 NS	6.85±5.7^&* NS	0.005	365±135 NS	975±565* NS	0.0001

Plasma renin activity (PRA); brain natriuretic peptide (BNP).The analysis among all eight groups studied showed significant differences for all results (P<0.001). *P<0.05; ^&P<0.001 (comparisons between groups A and B and groups C to H).

A significant association was found between the low-sodium intake and hospital readmissions [Odds ratio (OR)=2.46 (95% CI:1.84, 3.29), P<0.001].The group with normal sodium diet also had fewer deaths compared to all groups receiving a low-sodium diet combined.

Other Findings

Weight and Laboratory Parameters After 180 Days

Group	BW (kg)	Diuresis (ml per Day)	BUN (mg per dL)	Creatinine (mg per dL)	Natriuresis (mEq per Day)
Group A: NSD+250mg furosemide+1,000ml fluid intake (FI)	77±7	1,900±550^&	52±4.5^&	1.48±0.06^&	107±11
Group B: NSD+125mg furosemide+1,000ml FI P value	80±6 0.024	1,600±500^& 0.005	51±6.5^& NS	1.49±0.06^& NS	104±12 0.005
Group C: LSD+250mg furosemide+1,000m per day FI	79±5	1,400±600^&	102±5.5^&	2.0±0.09^&	77±9
Group D: LSD+125mg furosemide+1,000mg per day P value	81±9 0.025	1,350±400^& NS	93±3.5^& 0.0001	1.97±0.08^& NS	76±7 NS
Group E: NSD+250mg furosemide+2,000ml	80±11	1,550±650^&	71±3.4^&	1.75±0.07^&	98±16
Group F: NSD+125mg furosemide+2,000ml FI P value	83±10 NS	1,450±550^& 0.02	68±4.3^& 0.0001	1.74±0.06^& NS	101±15 NS
Group G: LSD+250mg furosemide+2,000ml FI	83±12	1,250±650^&	115±7.1^&	2.3±0.06^&	77±8
Group H: LSD+125mg furosemide+2,000ml FI P value	85±11 NS	1,150±450^& NS	101±5.3^& 0.0001	2.2±0.07^& 0.0001	76±9 NS

The analysis among all eight groups studied showed significant differences (P<0.001).^&P<0.001 (comparisons between group A and group B to H).

The Kaplan-Meir analysis showed an evident early (first 30 days) beneficial effect of this treatment (fluid restriction, normal Na, and higher furosemide dose), which was more consistent during the subsequent months of follow-up.

Author Conclusion:

The combination of a normal-sodium diet with high diuretic doses and fluid intake restriction, compared with different combinations of sodium diets with more modest fluid intake restrictions and conventional diuretic doses, leads to reductions in readmissions, neuro-hormonal activation and renal dysfunction.

Funding Source:

Other:

not described.

Reviewer Comments:

Some of the strengths and limitations reported by authors and IOM report 2013:

It was not possible to examine the effect of low sodium intake on health outcomes within sub-groups by dosage of furosemide and fluid restriction due to the small number of participants in the sub-groups
Limited generalizability due to eligibility criteria
No UNa measures
Unblinded
Patients received multiple written diets containing 1,840mg to 2,760mg per day Na prepared by dietitians
Patients assignment was decided at baseline before performing the measurements.

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.	Not given.
What was the target of sodium intake in the intervention and comparison groups?	Low sodium diet: 1,840mg per day (80mmol per day) Normal sodium diet: 2,760mg per day (120mmol per dayd).
Was the difference in sodium status (i.e., change in urinary sodium excretion) measured between groups? If so, please specify.	No
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.	No

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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	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
	2.2.	Were criteria applied equally to all study groups?	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
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	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
	3.5.	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")?	Yes
4.	Was method of handling withdrawals described?		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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	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?	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
	5.4.	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?	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
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	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
	6.6.	Were extra or unplanned treatments described?	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?	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
	7.2.	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?	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	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
	8.1.	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
	8.3.	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)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	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?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???