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The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial

Svend A Mortensen, Franklin Rosenfeldt, Adarsh Kumar, Peter Dolliner, Krzysztof J Filipiak, Daniel Pella, Urban Alehagen, Günter Steurer, Gian P Littarru, Q-SYMBIO Study Investigators
JACC Heart Failure 2014 2(6):641-649

Bibliography

PubMed
PMID 25282031
DOI
10.1016/j.jchf.2014.06.008
Funding
Partial support from the International Coenzyme Q10 Association, Pharma Nord ApS (Denmark), and Kaneka Corporation (Japan). The ISRCTN registry lists Pharma Nord ApS, the International Coenzyme Q10 Association, and Kaneka as funders.
Competing interests
The published paper states that all authors reported no relationships relevant to the contents of the paper. Industry funding is nevertheless important context for interpretation.

Study snapshot

DesignRandomized, double-blind, placebo-controlled multicenter trial
Model420 adults with moderate-to-severe chronic heart failure enrolled across 17 centers in Europe, Asia and Australia; predominantly NYHA class III, mean baseline LVEF about 31%, receiving standard heart-failure therapy.
Sample420 randomized: 202 CoQ10 and 218 placebo; 36 withdrew (22 CoQ10, 14 placebo); survival status was unknown for 4 patients in each arm at study end.
InterventionCoQ10 100 mg three times daily (300 mg/day) plus standard heart-failure therapy versus matching placebo capsules containing soy oil plus standard therapy.
Duration2 years
Endpoints16-week NYHA functional class; 16-week 6-minute walk test; 16-week NT-proBNP; 2-year time-to-first major adverse cardiovascular event (MACE); Cardiovascular mortality; All-cause mortality; Heart-failure hospitalization; 2-year NYHA class; Adverse events

What the study showed, in plain terms

Q-SYMBIO was a randomized, double-blind, multicenter trial of 420 people with moderate-to-severe chronic heart failure receiving standard therapy. Participants received CoQ10 100 mg three times daily (300 mg/day) or matching placebo for up to two years.

The prespecified short-term outcomes at 16 weeks—NYHA class, 6-minute walk distance and NT-proBNP—did not differ significantly between groups. The long-term composite MACE endpoint occurred in 15% of the CoQ10 group versus 26% of placebo, with an intention-to-treat hazard ratio of 0.50 (95% CI 0.32–0.80; p=0.003).

Cardiovascular mortality (9% vs 16%; p=0.026), all-cause mortality (10% vs 18%; p=0.018) and heart-failure hospitalization (p=0.033) also favored CoQ10. NYHA class improved at two years (p=0.028). Adverse events were numerically lower with CoQ10—26 patients (13%) versus 41 (19%) with placebo—but this difference was not statistically significant (p=0.110).

Key findings

Primary short-term outcomes: No significant between-group change at 16 weeks in NYHA functional class, 6-minute walk test or NT-proBNP.

Primary long-term outcome: MACE occurred in 30/202 (15%) CoQ10 participants versus 57/218 (26%) placebo participants; HR 0.50, 95% CI 0.32–0.80, p=0.003 by intention-to-treat analysis.

Mortality: Cardiovascular mortality was 9% vs 16% (p=0.026), and all-cause mortality was 10% vs 18% (p=0.018), favoring CoQ10.

Heart-failure morbidity and symptoms: Heart-failure hospital stays were significantly less frequent with CoQ10 (p=0.033), and NYHA class was significantly better at two years (p=0.028).

Safety: 26 participants (13%) in the CoQ10 arm and 41 (19%) in the placebo arm experienced reported adverse events (p=0.110). Gastrointestinal disturbances were 2 vs 8, respectively. The blinded DSMB evaluated adverse events and the clinical endpoint committee adjudicated endpoints.

Analysis set and attrition: All randomized participants remained in the intention-to-treat analysis despite 36 withdrawals. Four participants in each arm were lost to final survival follow-up; a conservative sensitivity analysis still favored CoQ10 (HR 0.64, 95% CI 0.42–0.98; p=0.038).

What this study can and cannot tell us

The trial stopped before reaching its planned enrollment of 550 because recruitment was slow; 420 patients were randomized after an enrollment period spanning 2003–2010 across 17 centers.

The authors noted that roughly 20% of participants in both arms were stabilized without diuretics, so some may have had milder NYHA class II disease than classified. This may partly explain the lower-than-expected death rate.

There were 87 primary MACE events and 60 deaths, so the large relative treatment effects arose from a modest event count. The study also predates current contemporary guideline-directed heart-failure pharmacotherapy.

The trial received partial industry/industry-association support from Pharma Nord, Kaneka and the International Coenzyme Q10 Association. The paper reports no author relationships relevant to the article, but funding remains relevant when weighing the evidence.

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