Heart Failure

HF: Carnitine (2007)

Citation:

Rizos I. Three-year survival of patients with heart failure caused by dilatedcardiomyopathy and L-carnitine administration. Am Heart J. 2000 Feb; 139 (2 Pt. 3): S120-123.

 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To determine the effect on mortality rate and other efficacy parameters of long-term L-carnitine administration for the treatment of heart failure in adults, attributable to dilated cardiomyopathy.

Inclusion Criteria:
  • Dilated cardiomyopathy
  • Classified as stable (sinus rhythm), according ot the New York Heart Association function class III to IV
  • Able to perform treadmill exercise.
Exclusion Criteria:
  • Ischemic heart disease (defined as occlusion more than 50%)
  • Significant valvular heart disease
  • Atrial fibrillation
  • Alcohol abuse.
Description of Study Protocol:
  • A double-blind placebo-controlled study for the initial three-month period, followed by an unblinded study for the remainder of the three years
  • A total of 80 patients were randomly assigned to treatment with L-carnitine or placebo after a baseline hemodynamic study
  • All patients received conventional therapy for heart failure that included diuretics, digoxin and angiotensin-converting enzyme inhibitors
  • After entering the study, patients were randomly assigned to receive either oral L-carnitine (two g per day) or placebo for three months. The study was unblinded at the end of the three months.
  • A Kaplan-Meier survival analysis, presented as a cumulative mortality curve, was used to describe patient death
  • The log-rank test was used to compare mortality between the two groups.
Data Collection Summary:
  • Hemodynamics were performed during the stabilization phase before patients were entered into the study, at baseline, one month, three months and at approximate six-month intervals throughout the remainder of the three-year study
  • Hemodynamic studies included coronary angiography with left ventriculography (entry-only), right catheterization and cardiopulmonary exercise tests, according to the Weber protocol
  • Measured parameters included ejection fraction, Weber classification, maximal time of cardiopulmonary exercise test, peak VO2 consumption, arterial and pulmonary blood pressure and cardiac output 
  • The end point was death at three years, comparing the two groups. The clinical end point was the results of the hemodynamic tests.
Description of Actual Data Sample:
  • Mean age of participants in the L-carnitine group (N=42) was 50 years and 48 years in the placebo group (N=38)
  • There were 19 males and 23 females in the L-carnitine group vs. 20 males and 18 females in the placebo group
  • All participants were residents of Greece
  • After a mean of 33.7 months, 70 patients remained in the study: 33 in the placebo and 37 in the L-carnitine group
  • Five patients left the study from each group, including one patient in the placebo group who underwent cardiomyoplasty
  • Six patients died in the placebo group: Five from pump failure and one from sudden cardiac death
  • The one death in the L-carnitine group was from documented sustained ventricular tachycardia despite resuscitation.
Summary of Results:
  • There were no statistically significant differences in baseline characteristics between the two groups for the clinical and hemodynamic parameters
  • The survival analysis of the remaining 70 subjects showed that the patients' survival was statistically significant in favor of L-carnitime (0≤0.04). The survival rates began to diverge at 12 months. The three-year mortality rate was 18% for the placebo group vs. 3% in the L-carnitine group. 
  • At three months, there was a statistically significant difference in favor of the L-carnitine patients for the Weber classification, maximal time of cardiopulmonary exercise, peak oxygen consumption, arterial and pulmonary blood pressure and cardiac output
    • One patient in the L-carnitine group did not maintain sinus rhythm and had atrial flutter requiring cardioversion
    • Seven of the 33 patients in the placebo group had atrial fibrillation which persisted in five; two maintained a sinus rhythm after carioversion and amiodarone treatment.
  • Three of the 37 patients who completed the study had minor gastrointestinal problems but were not withdrawn from the study.
Author Conclusion:
  • Results suggest that L-carnitine may improve the functional status of patients with moderate to severe heart failure attributable to dilated cardiomyopathy
  • A large randomized, placebo-controlled trial is required to fully assess the usefulness of L-carnitine administration in this setting.
Funding Source:
University/Hospital: University of Athens Medical School (Greece)
Reviewer Comments:
  • Study number is small
  • Population is from Greece
  • Population is a specific category of heart failure
  • Study indicates that 12 months is needed to see differences in mortality rates
  • Clinical and hemodynamic results were only for a three-month period, while the mortality results are for three years.
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? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  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")? No
4. Was method of handling withdrawals described? No
  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? No
  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
  5.1. 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? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? No
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? No
  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? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? No
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  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? N/A
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? ???
  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? No
  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? ???
  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
  8.5. 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
  8.7. 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
  9.1. 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? ???