Trial data of CoQ10 therapy in HF
There have been numerous observational reports in the last few decades reporting the usefulness of CoQ10 in improving HF symptoms, including ejection fraction, left ventricular size and quality of life. However, these studies had several design shortcomings, which have prevented their translation into clinical practice.46–53
Several clinical trials report comparisons of CoQ10 efficacy versus placebo. While some report no advantage over placebo, others conclude that CoQ10 supplementation improves systolic function and reduces ventricular size.54–66 Thus, due to small sample sizes and concomitant large effect sizes in these trials, it may be difficult to make certain statements regarding advantages and disadvantages of CoQ10 therapy. Also, it is difficult to assess the benefits of CoQ10 with respect to severity and aetiology of HF, and to segregate responders versus non-responders. Subsequently, to overcome these limitations, the trial data were pooled using meta-analysis to better understand the benefits of CoQ10 therapy.
Initial meta-analysis by Soja and Mortensen67 reported that, compared to HF patients in the placebo group, patients treated with CoQ10 achieved a better ejection fraction, stroke volume, cardiac output, cardiac index and end diastolic volume index (92% (p<0.0001), 76% (p<0.005), 73% (p<0.05), 87% (p<0.0001) and 88% (p<0.0001), respectively). In another analysis by Sander et al, with CoQ10 doses ranging from 60–200 mg/day, it was shown that there was a 3.7% net improvement in ejection fraction (1.59 to 5.77; p<0.00001). Cardiac output improved by an average of 0.28 L/min (0.03 to 0.53; p=0.96). Also, an increasing trend was demonstrated in stroke volume and stroke index, which increased by an average of 5.68 mL/m2 (1.02 to 10.34; p=0.28). Further subgroup analysis revealed that ejection fraction improved by 6.74% (CI 2.63% to 10.86%) without angiotensin converting enzyme inhibitor (ACEi) therapy as compared to a mere 1.16% change (CI −0.39% to 2.71%) with use of ACEI.68 Another subgroup analysis showed that ejection fraction improved by 3.69% (CI 2.30% to 5.07%) when patients with severe HF (NYHA IV) were excluded, as compared to 2.17% (CI 0.28% to 4.05%) improvement in the absence of such exclusion,68 suggesting that initiating CoQ10 therapy early could help salvage cardiac myocyte function.
Fotino et al reported similar results in a meta-analysis; CoQ10 supplementation resulted in a pooled mean net increase in ejection fraction of 3.67% (95% CI 1.60% to 5.74%, p<0.001). A post hoc subgroup analysis showed change in ejection fraction was significant for participants with a baseline ≥30% (net change: 4.82; 95% CI 3.01 to 6.59), but was not significant for participants with a baseline <30% (net change: 0.40; 95% CI −0.91 to 1.70), further suggesting the benefits of early CoQ10 therapy.69
These meta-analyses hence suggest that supplemental CoQ10 can confer functional benefits in heart failure, but that these benefits tend to be greater in the absence of concurrent ACEI therapy and in patients with less severe dysfunction. These limitations may explain the failure of some modest-sized studies to confirm benefit for CoQ10.
Another possible benefit of CoQ10 supplementation may be its ability to improve exercise capacity in those treated with statins.70 As exercise capacity is a strong predictor of prognosis, this might be another advantage of CoQ10 supplementation.71
Despite favourable effects on surrogate endpoints with CoQ10 supplementation, the impact of CoQ10 on hard endpoints in HF, such as mortality, has long remained unclear. Fortunately, more clarity in this respect was provided with the recently released results from the Q-SYMBIO trial, a prospective, randomised, double-blind, placebo-controlled, multicentre trial of CoQ10 as adjunctive treatment of chronic HF, focusing on changes in symptoms, biomarker status and long-term outcomes. This trial included 420 patients with moderate to severe CHF, who were randomly assigned to receive, for a 2-year period, CoQ10 100 mg three times daily (n=202) or placebo (n=218), as an adjunct to standard therapy. No significant differences were observed for secondary end points (NYHA functional class, visual analogue scale score for dyspnoea, fatigue and improvement in symptoms, N-terminal pro-brain natriuretic polypeptide (NT-proBNP) and 6 min walk test) between two groups at 16 weeks. However, on analysing long-term primary end points with an intention to treat analysis at week 106, there was a significant reduction in MACE in the CoQ10 group (15%, n=30 vs 26%, n=57; corresponding to relative reduction of 43% with p=0.005; with HR 0.50; 95% CI 0.32 to 0.80; p=0.003 calculated from a Cox regression analysis stratified by centre). Additionally, the secondary endpoints at week 106 were better in the CoQ10 group—NYHA class improvement by 1 grade (58%, n=86 vs 45%, n=68; p=0.028) and serum NT-proBNP reduction (60%, 1137 pg/mL vs 52%, 881 pg/mL; p>0.05). The patients in the CoQ10 group had significantly fewer cardiovascular deaths (9%, n=18 vs 16%, n=34; corresponding to 43% relative reduction with p=0.039; with HR 0.51; 95% CI 0.28 to 0.92; p=0.026 calculated from a Cox regression analysis stratified by centre) and hospital stays for heart failure (8%, n=17 vs 14%, n=31, HR 0.51; 95% CI 0.27 to 0.95; p=0.033). Also, in the CoQ10 group there were significantly fewer all-cause deaths reported (10%, n=21 vs 18%, n=39; corresponding to 42% relative reduction with p=0.036; with HR 0.51; 95% CI 0.30 to 0.89; p=0.018 calculated from a Cox regression analysis stratified by centre). Additionally, the number of adverse events tended to be less in the CoQ10 group (13%, n=26 vs 19%, n=41; p=0.110).8
In summary, the long-term supplementation of CoQ10 in patients of HF seems safe, appears to produce symptomatic improvements, and, more importantly, has been found to significantly reduce MACEs and mortality. Larger randomised studies will be needed to confirm the results of the Q-SYMBIO trial in patients with HF.