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The Q-SYMBIO clinical trial was a multi-center randomized placebo-controlled double-blind clinical trial that was reported in the Journal of the American College of Cardiology: Heart Failure in September 2014.

The trial name Q-SYMBIO reflects the focus on the following elements in the clinical trial: Q = Q10 and SYMBIO = SYMptoms, BIomarker status [Brain-Natriuretic Peptide], and long-term Outcome [hospitalizations/mortality].

Purpose
The purpose of the study was to assess the effect of the adjuvant therapy drug Coenzyme Q10 on several short-term and long-term endpoints in a total of 420 chronic heart failure patients enrolled in 17 cardiology centers in Europe, Asia, and Australia from 2003 to 2010.

Dosage
The dosage of Coenzyme Q10 administered to the active treatment arm of the Q-SYMBIO trial was 100 milligrams three times daily, a dosage large enough to raise blood serum levels of Q10 significantly.

Patients
The patients were selected for the Q-SYMBIO trial if they had chronic heart failure in New York Heart Association functional classes III (marked limitation of physical activity) or IV (unable to carry out any physical activity without discomfort).

The age of the patients in years was 62.3 =/- 12. The ratio of male patients to female patients was roughly three to one.

The mean duration of heart failure was around three years in both arms of the trial, and the baseline ejection fraction and six-minute-walking-time distances were equal between the groups.

90% of the patients in the study were receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and 75% of the patients in the study were receiving beta-blockers.

The dosages of the medications were only infrequently modified during the trial, so it is unlikely that minor changes in medication should have influenced the outcome of the trial.

Short-Term Effects (16 weeks of treatment)
At week 16, there were improvements in NYHA classification, VAS score, and 6MWT in both treatment groups, but there were no significant differences between the groups. There was a trend with a 20% reduction of NT-proBNP in the CoQ10 group and a proportional rise of 12% in the placebo group.

Retrospectively, at this time Cardiovascular Deaths were already significantly lower in the CoQ10 group, but this was not a pre-specified endpoint at week 16.

Long-Term Effects (106 weeks of treatment)
Major Adverse Cardiovascular Events

The number of Major Adverse Cardiovascular Events (MACE), which was the primary long-term endpoint in the trial, was statistically significantly fewer (p < 0.005) in the Q10 treatment arm (N = 30, 15%) than in the placebo arm (N = 57, 26%), corresponding to a 42.3% relative reduction in risk of MACE events.

Cardiovascular Mortality

The total number of cardiovascular deaths during the 106 weeks of the study was statistically significantly lower (p = 0.026) in the Q10 treatment arm (N = 18, 9%) than in the control arm (N = 34, 16%), a relative reduction of 43.8% in risk of cardiovascular death.

All-cause Mortality

Altogether, there were statistically significantly fewer (p = 0.018) deaths from all causes in the Q10 treatment arm (N = 21, 10%) than in the control arm (N = 39, 18%), a relative reduction of 44.4%.

Hospital Stays for Heart Failure

The number of hospital stays for heart failure during the 106 weeks was statistically significantly lower (p = 0.033) in the Q10 treatment arm (N = 17, 8%) as compared to the control arm (N = 31, 14%), a relative reduction of 42.8%.

Discussion of the Results
Mortensen et al hypothesize that the dosage (100 mg three times daily) and the formulation of the Q10 used in the Q-SYMBIO clinical trial may have resulted in the patients' reaching a required "therapeutic threshold in serum and tissue of CoQ10" needed to reduce the number of major adverse cardiovascular events.

The formulation used in the trial has been demonstrated to have good bio-availability in controlled studies.

The Morisco Clinical Trial
The results of the Q-SYMBIO clinical trial build on the earlier results from the multi-center randomized placebo-controlled double-blind clinical trial that was reported in 19932 by Morisco et al. That study enrolled 641 congestive heart failure patients (again, patients classified NYHA III and IV) randomly in a placebo arm and in a Q10 treatment arm in which the patients received a daily dosage of 2 mg per kilogram of body weight for the period of a year. The study focused on the need of hospitalization and on the incidence of life-threatening arrhythmias, pulmonary edema, and cardiac asthma.

The number of patients in the Morisco study who required hospitalization for worsening heart failure was significantly smaller (p < 0.001) in the Q10 treatment arm (n = 73, 22.8%) than in the control arm (n = 118, 36.6%), a relative reduction of 37.7% in required hospitalizations.

Moreover, in the Morisco study, the number of the episodes of pulmonary edema (20/319, 6.3% versus 51/322, 15.8%) and cardiac asthma (97/319, 30.4% versus 198/322, 61.5%) was significantly reduced (p < 0.001) in the Q10 arm as compared to the control arm.

The Morisco study authors concluded that their results demonstrated that adjuvant treatment with Coenzyme Q10 in addition to conventional therapy significantly reduced the number of hospitalizations for worsening of heart failure and the incidence of serious complications in patients with chronic congestive heart failure.

Meta-analyses of the Efficacy of Q10 in Heart Failure
Altogether, meta-analyses by Soja et al, Sander et al , and Fotino et al have found significant improvements in ejection fraction. A total of 21 placebo-controlled trials have evaluated the efficacy of CoQ10 in heart failure, including Q-SYMBIO. Only three of these studies did not find any effects, and the outcome in those three trials could possibly be attributed to low compliance rates in the treatment arm or to flaws in the study design.

Elderly Individuals
It is known that the ability of the human body to synthesize Coenzyme Q10 declines with age8 and that it may therefore be necessary to supplement the diet of elderly individuals with Q10. Alehagen et al have reported on the results of a five-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 889. 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo.

There was a significant reduction (p = 0.015) of cardiovascular mortality in the Q10 treatment arm as compared with the placebo group (5.9% vs. 12.6%, a relative reduction of 53%)9. The long-term supplementation with a combination of 200 mg/day of coenzyme Q10 capsules (Bio-Quinon 100 mg twice daily, Pharma Nord, Vejle, Denmark) and 200 ?g/day of organic selenium yeast tablets (SelenoPrecise 200 ?g, Pharma Nord, Vejle, Denmark) reduced cardiovascular mortality. The positive effects could also be seen in N-terminal pro b-type natriuretic peptide (NT-proBNP) levels and on echocardiography9.

Individuals Taking Statins
Statins are known to block the biological pathway that produces both cholesterol and Coenzyme Q10. Consequently, patients taking statins may need to supplement with Q1010.

Biological Mechanisms Explaining the Improvement of Heart Failure Symptoms

Mortensen et al posit four explanations for the effect of Q10 on the improvement of symptoms and survival of chronic heart failure patients:

1. Additional available Q10 may improve the respiratory rate in heart cells10.

2. Additional available Q10 may increase energy production in the heart muscle cells, thus impeding the "vicious metabolic cycle" in heart failure11.

3. Additional available Q10 may increase the stability of the "mitochondrial permeability transition pore" and thereby protect the heart muscle against apoptotic cell death12.

4. Additional available Q10 may improve endothelial function13 and may protect the heart muscle against ischemic damage14.