HF: Carnitine (2007)
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.
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.
- Dilated cardiomyopathy
- Classified as stable (sinus rhythm), according ot the New York Heart Association function class III to IV
- Able to perform treadmill exercise.
- Ischemic heart disease (defined as occlusion more than 50%)
- Significant valvular heart disease
- Atrial fibrillation
- Alcohol abuse.
- 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.
- 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.
- 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.
- 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.
- 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.
|University/Hospital:||University of Athens Medical School (Greece)|
- 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
|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|
|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?||???|