Coenzyme Q for CHF
Coenzyme Q for CHF
Abstract & Commentary
Synopsis: Despite doubling of plasma coenzyme Q levels for three months, there was no change in subjective or objective parameters of heart failure in those patients with left ventricular systolic dysfunction.
Source: Watson PS, et al. J Am Coll Cardiol 1999; 33:1549-1552.
Coenzyme Q is a fat-soluble quinone found in heart mitochrondria. It is involved in oxidative phosphorylation and is an antioxidant. Since it is depleted in heart failure, it has been postulated that coenzyme Q may be useful for treatment. Several uncontrolled observational studies have shown improvement in symptoms and cardiac function measures after oral administration of coenzyme Q. Thus, Watson and associates conducted a randomized, placebo-controlled, double-blind trial in 30 patients with chronic stable heart failure and ejection fraction less than 35% on maximum doses of angiotension-converting enzyme inhibitors. Those randomized to coenzyme Q received 33 mg tid for 12 weeks and then were crossed over to placebo. Those randomized to placebo did the opposite. Thus, each patient served as his or her own control. Echocardiograms and right heart catheterization were performed at entry and at the end of each treatment period. Also, the Minnesota "Living with Heart Failure" questionnaire and plasma coenzyme Q levels were done at the same times. Death or transplantation kept three patients from completing the study, but coenzyme Q was safe and produced no adverse side effects. In the remaining 27 patients, ejection fraction averaged 26% at entry and was 31% at the end of both treatment periods (P = NS). Pulmonary wedge pressure mean was 16 mmHg and did not change on either therapy. Plasma coenzyme Q increased from 903 at entry to 2029 nmol/L on active therapy. The Minnesota questionnaire was unchanged by either therapy. Watson et al concluded that despite doubling of plasma coenzyme Q levels by oral therapy for three months, there was no change in subjective or objective parameters of heart failure in these patients with left ventricular systolic dysfunction.
Comment by Michael H. Crawford, MD
We do not usually cover negative studies in Clinical Cardiology Alert, but I have had so many patients ask me about coenzyme Q that I thought this one was worth discussing. This is a well-designed clinical study powered to detect an increase in ejection fraction of 5%. No significant change in subjective parameters, echocardiographic left ventricular performance, or right heart catheterization measures was found, despite more than doubling plasma coenzyme Q levels. Obviously, the pathophysiology of congestive heart failure is more complex than the deficiency of one mitochondrial substance.
The study can be criticized. Perhaps three months is insufficient time to observe a change. However, previous studies with coenzyme Q and other substances have demonstrated changes in this period. Since myocardial levels of coenzyme Q were not measured (no biopsies), it is possible that plasma levels do not reflect tissue levels and higher doses of drug are needed. However, this dosage has shown changes in other studies. Finally, it may be that if coenzyme Q is administered earlier in the course of a patient’s disease, it will be more effective. Since coenzyme Q did not appear to be harmful, there seems to be no reason to prohibit its use, but patients with heart failure should be advised that a well-done study has not shown benefit and they may wish to avoid the expense of this agent.
A randomized controlled trial in CHF patients showed that coenzyme Q:
a. increased ejection fraction.
b. reduced pulmonary wedge pressure.
c. improved quality of life.
d. had no subjective or objective effects.
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