Heart Failure

HF: Alcohol Intake (2007)

Citation:

Cooper HA, Exner DV, Domanski MJ. Light-to-Moderate Alcohol Consumption and Prognosis in Patients With Left Ventricular Systolic Dysfunction, J Am Coll Cardiol. 2000, 35: 1,753-1,759.

 
Study Design:
Retrospective analysis
Class:
B - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To assess the relationship between baseline alcohol consumption and prognosis in patients with left ventricular (LV) dysfunction. 

Inclusion Criteria:
  • Participation in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention and Treatment trials
  • Ejection fraction values equal to or less than 0.35
  • Consumption of one to 14 drinks per week or no alcohol consumption
  • Aged 21 to 80 years
  • No history of intolerance to enalapril.
Exclusion Criteria:
  • Recent myocardial infarction, significant valvular heart disease or other serious comorbid illness.
  • Chronic alcoholism if deemed likely to interfere with compliance
  • Clinically unstable
  • Recent change in heart failure (HF) medications.
Description of Study Protocol:
  • Recruitment: All SOLVD participants
  • Design: Retrospective review.

Statistical Analysis

  • Data from the Prevention and Treatment Trials were pooled after no interaction was found between trial assignment and alcohol consumption, with regard to mortality
  • Evidence of statistical interaction between alcohol consumption and the etiology of LV dysfunction was observed (P=0.05), thus ischemic and non-ischemic patients were separately evaluated
  • Continuous characteristics are presented as means ±SD
  • Pairwise differences were evaluated using a chi-square test or T-test
  • Death from any cause was used as the primary end point in this analysis and additional analyses were performed for cause-specific mortality end points and hospitalization for heart failure
  • Incidence rates were calculated as the number of events per 100 person-years of follow-up 
  • Multivariate Cox proportional hazards models were used to assess the independent relationship between alcohol consumption and mortality. Relative risk (RR) estimates and 95% confidence intervals (CI) were obtained from the Cox models.
  • Two-sided P-values below 0.05 were considered to be significant
  • All analyses were performed using Stata:Release 6.0.
Data Collection Summary:

Timing of Measurements

Baseline and 33.4±14.3 months follow-up for end points.

Dependent Variables

  • Cause of death was determined by the principal investigator at each clinical site. Deaths from cardiovascular causes were classified as caused by pump failure; probable arrhythmia with some antecedent worsening of heart failure (HF); probable arrhythmia with no antecedent worsening of HF; fatal myocardial infarction (MI); other cardiac, stroke or vascular cause; or unknown.
  • In this analysis, all deaths from pump failure and probable arrhythmia with some antecedent worsening of HF were classified as deaths caused by progressive HF
  • Arrhythmic deaths were limited to those classified as probable arrhythmia with no antecedent worsening of HF
  • Two pre-defined indicators of the progression of HF were death from progressive HF and hospitalization for HF
  • Deaths from non-cardiovascular causes were classified as a cancer of a non-cancer cause
  • Baseline age, blood pressure and LV ejection fraction (EF) values were assessed as continuous variables. All remaining variables including study drug allocation (enalapril/placebo), were assessed as dichotomous variables.
  • The NYHA functional class symptoms were grouped as Class I, Class II or Class III/IV. The etiology of LV systolic dysfunction was classified as ischemic or other by the enrolling physician. 

Independent Variables

  • Alcohol consumption was determined at baseline by self-report, given as the average number of alcoholic drinks per week for the previous two years
  • Patients were classified as non-drinkers (average of zero drinks per week), light-to-moderate drinkers (one to 14 drinks per week) and heavy drinkers (over 14 drinks per week).
Description of Actual Data Sample:
  • Initial N: 6,797
  • Attrition (final N): 6,313 (19% of the non-drinkers and 9% of the light-to-moderate drinkers were women; P<0.001)
  • Age: 61±10 years for the non-drinkers and 59±10 for the light-to-moderate drinkers; P<0.001
  • Ethnicity: 82% of the non-drinkers and 77% of the light-to-moderate drinkers were white; P<0.001. Ethnicity of the remainder was not described.

Anthropometrics

  • Mean EF was nearly identical in both groups and a similar proportion of both groups had ischemic cardiomyopathy. The proportion of participants who were current smokers was somewhat higher among light-to-moderate drinkers than among non-drinkers (P<0.001).
  • A history of diabetes and hypertension was higher in the non-drinkers (26% vs. 12%, P<0.001 and 41% vs. 37%, P<0.01; respectively).
  • Non-drinkers had a higher usage of diuretics and digoxin (P<0.001) and a lower usage of aspirin (P<0.01) and beta-blockers (P<0.05). There was a greater percentage of light-to-moderate drinkers who were classified as NYHA Class I (P<0.001).
Summary of Results:

Cause of Death

Non-drinkers

Light-to-Moderate Drinkers

 

Number (Percentage)

Incidence*

Number (Percentage)

Incidence*

All Causes

963 (25.9)

9.4

531 (20.5)

7.2**

Cardiovascular

843 (22.7)

8.3

479(18.5) 

6.5**

 

Progressive HF

397 (10.7)

3.9

225 (8.7)

3.0**

   

Arrhythmia

248 (6.7)

2.4

141 (5.4)

1.9**

   

MI

140 (3.8)

1.4

58 (2.2)

0.8**

Other Cardiovascular

58 (1.6)

0.6

55 (2.1)

0.8

Non-Cardiovascular

120 (3.2)

1.2

52 (2.0)

0.7**

   

Cancer

50 (1.3)

0.5

28 (1.1)

0.4

   

Non-Cancer

70 (1.9)

0.7

24 (0.9)

0.3**

* Rate per 100 person-years of follow-up. Unadjusted data.
** P<0.05.

Other Findings

  • Before adjustment for baseline differences, light-to-moderate alcohol consumption, compared with no alcohol consumption, was associated with a lower risk of death (RR, 0.75; 95% CI, 0.68 to 0.84; P<0.001)
  • Other predictors of a lower risk of death among those patients who were not heavy drinkers included the use of anti-platelet agents, beta-blockers and randomization to the study drug Enalapril
  • Predictors of a higher risk of death were advanced age, non-white race, lower EF, NYHA Functional Class III or IV, previous hypertension, diabetes, current smoking and use of digoxin, diuretics and antiarrhythmic drugs
  • Ishemic LV Dysfunction: After adjusting for baseline differences in age, gender, EF, NYHA functional class and study drug assignment
    • Light-to-moderate alcohol vs. no alcohol consumption associated with decreased risk of all-cause mortality (RR, 0.78; 95% CI, 0.69 to 0.89, P<0.001). This association remained significant after additional adjustments for potential confounders.
    • Light-to-moderate alcohol consumption was associated with a reduced risk for fatal MI (P<0.001) and non-cardiovacular death (P<0.01).
  • Non-Ischemic LV Dysfunction
    • Trend toward an increased risk of hospitalization for HF (P=0.1)
    • Light-to-moderate alcohol consumption was not significantly associated with any of the cause-specific modes of death, although there were trends toward a reduced risk of arrhythmic death (0.62; CI, 0.38 to 1.00; P=0.05) and an increased risk of other cardiovascular death (2.06; CI, 0.98 to 4.33; P=0.06)
  • Light-to-moderate alcohol consumption was not associated with an increase in the risk of death from progressive HF in either ischemic or non-ischemic group.
Author Conclusion:
  • Light-to-moderate alcohol consumption appears to be safe in patients with LV systolic dysfunction and it may reduce the risk of death and the risk of fatal MI in patients with ischemic LV dysfunction
  • Patients with LV dysfunction, who consume two or less drinks per day should not be advised to discontinue drinking alcohol for the purpose of reducing cardiovascular morbidity or mortality
  • There is insufficient evidence to recommend the use of alcohol to patients with LV dysfunction who do not currently drink alcohol
  • Heavy alcohol consumption should continue to be discouraged for patients with LV systolic dysfunction, because of the clear increase in non-cardiovascular and total mortality shown in previous studies and because of the strong evidence that heavy alcohol consumption can lead to impairment of LV contractile function.
Funding Source:
Government: NIDDK/NIH, MRC Canada
University/Hospital: Georgetown University Medical Center
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:
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? 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
  3.1. 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? No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? No
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  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? 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? Yes
  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? Yes
4. Was method of handling withdrawals described? Yes
  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%.) 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
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? 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? 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? No
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) No
  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.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? No
  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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? 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
  6.3. 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
  6.4. 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? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  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? 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
  7.4. 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)? N/A
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? 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
  8.6. 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? N/A
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
  9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
  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