Coenzyme Q10 supplementation reduces HF admissions and improves survival: Q-SYMBIO
"Some, however, considered the recommendations to alter clinical practice on the basis of this 420-patient clinical trial premature......reserve judgment on the data until they have stood up against the scrutiny of the peer-review process......Clinicians should view implausibly large treatment effects observed in small underpowered trials with skepticism, as they are seldom replicated in subsequently conducted large controlled trials.....why the Q-SYMBIO trial took more than 10 years to complete. The trial design was first published in 2003......there are some questions that need to be answered before any heart-failure patient should start taking CoQ10 supplements. Specifically, it is not known exactly what "current pharmacologic therapy" entailed for the treated patients. Like Kaul, he would like to see the paper published in order to determine the background regimens, but if it turns out that they were receiving ACE inhibitors/angiotensin-receptor blockers and beta-blockers and CoQ10 still reduced HF admissions and mortality, "that would certainly be a big deal.""|
May 31, 2013 Michael O'Riordan
Lisbon, Portugal - In a study bound to be scrutinized when it is finally published, the Q-SYMBIO randomized, controlled, double-blind clinical trial garnered a fair deal of attention this past week when investigators reported excellent clinical outcomes in chronic heart failure patients treated with coenzyme Q10 (CoQ10).
"Metabolic modulation and energetic manipulation in the failing heart is the next frontier of heart-failure management. I want this stuff to work.
Presenting the study at Heart Failure Congress 2013 of the European Society of Cardiology Heart Failure Association, lead investigator Dr Svend Aage Mortensen (Copenhagen University Hospital, Denmark) reported that, at two years, major adverse cardiovascular events (MACE), a composite of unplanned hospitalization due to worsening heart failure, cardiovascular death, and the need for urgent cardiac transplantation and mechanical support, occurred in 14% of patients treated with CoQ10 compared with 25% of patients who received a placebo, a statistically significant difference (p=0.003). All-cause mortality was also significantly lower in the CoQ10-treated patients, with 9% dying compared with 17% in the placebo arm (p=0.01).
In addition to these outcomes, the Q-SYMBIO investigators reported that cardiovascular mortality and admissions for heart failure were significantly lower in those who received CoQ10. In their conclusions, the researchers stated that "CoQ10 should be considered as a part of the maintenance therapy of patients with chronic heart failure."
Yellow light: Go slow, caution urged
Some, however, considered the recommendations to alter clinical practice on the basis of this 420-patient clinical trial premature. Dr Sanjay Kaul (Cedars-Sinai Medical Center, Los Angeles), for example, said he wants to reserve judgment on the data until they have stood up against the scrutiny of the peer-review process. He noted that the mortality data were first presented at the meeting of the International Coenzyme Q10 Association last November, but these are yet to be published.
"Clinicians should view implausibly large treatment effects observed in small underpowered trials with skepticism, as they are seldom replicated in subsequently conducted large controlled trials," Kaul told heartwire. "The examples of vesnarinone in heart failure, [glucose-insulin-potassium] GIK post-STEMI, and perioperative beta-blockers in high-risk vascular surgery quickly come to mind. None of the impressive preliminary results could be replicated. If a finding appears to be 'too good to be true,' it usually is."
One curiosity that also needs to be addressed, added Kaul, is why the Q-SYMBIO trial took more than 10 years to complete. The trial design was first published in 2003. heartwire asked Mortensen to comment on the study and the results, but he declined, saying he wants to wait until after the study is published to discuss the findings.
What other treatments were they taking?
CoQ10 is an antioxidant involved in cellular-energy production. It is postulated that heart-failure patients, who have a measurable deficiency in CoQ10, would benefit from receiving the supplement.
The Q-SYMBIO study included 202 patients randomized to CoQ10 and 218 patients randomized to placebo. All patients included in the study had moderate to severe heart failure (NYHA class 3 or 4) and were receiving "current" pharmacologic therapy. Patients had an average ejection fraction of 31%, and the average age was 62 years. Within three months of treatment, investigators observed a trend toward lower levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The clinical improvements in MACE were observed after two years of receiving 100 mg of CoQ10 three times daily compared with those who received the placebo. In addition, 44% of those who received CoQ10 had an improvement in NYHA class compared with 45% of those who received placebo (p=0.047).
To heartwire, Dr David Kao (University of Denver, Aurora, CO) also said there are some questions that need to be answered before any heart-failure patient should start taking CoQ10 supplements. Specifically, it is not known exactly what "current pharmacologic therapy" entailed for the treated patients. Like Kaul, he would like to see the paper published in order to determine the background regimens, but if it turns out that they were receiving ACE inhibitors/angiotensin-receptor blockers and beta-blockers and CoQ10 still reduced HF admissions and mortality, "that would certainly be a big deal."
Still, even with all the relevant information, Kao said the trial needs to be replicated in a larger cohort. To substantiate any claims of mortality reduction, the next trial, if Q-SYMBIO stands up once published, would need to include several thousand patients at least.
"I think this is a fascinating area," Kao told heartwire. "Metabolic modulation and energetic manipulation in the failing heart is the next frontier of heart-failure management. I want this stuff to work. The CoQ10 story has been murky, and there just isn't quite enough information available on this trial yet to know how to interpret it."
The study was funded by the International Coenzyme Q10 Association, as well as Kaneka and Pharma Nord, maker of products that contain CoQ10. Kaul and Kao report no conflicts of interest related to the study.
CoQ10 Promising for Chronic Heart Failure
By Todd Neale, Senior Staff Writer, MedPage Today
Published: May 28, 2013
LISBON -- When added to conventional therapies, a supplement containing the antioxidant coenzyme Q10 (CoQ10) improved outcomes in patients with moderate-to-severe chronic heart failure, a small placebo-controlled trial showed.
At 2 years, the patients who received the supplement had a significantly lower rate of major adverse cardiovascular events than those who did not take CoQ10 (14% versus 25%), which worked out to a doubling in freedom from those events (HR 2.o, 95% CI 1.3-3.2), according to Svend Aage Mortensen, MD, DMSc, of Copenhagen University Hospital.
Both all-cause and cardiovascular mortality were significantly reduced in the supplement group, and there was a nonsignificant trend toward fewer adverse events (P=0.073), he reported at the Heart Failure Congress here.
Based on the findings, committees in charge of crafting practice guidelines might think about including information about CoQ10 as an option to be used with other heart failure therapies, Mortensen said in an interview with MedPage Today.
"CoQ10 could be considered as adjunctive treatment in heart failure," he said.
But Aldo Maggioni, MD, who was on the task force that developed the 2012 European Society of Cardiology heart failure guidelines, told MedPage Today that the results were not practice changing, pointing to the low number of patients included in the trial (420) and the low number of MACE events (84).
"You cannot change clinical practice all over Europe basing your conclusion on that," he said.
Maggioni said that if no other data were to become available, updated guidelines would probably mention the results of the current study -- which he called interesting and encouraging -- without making a specific recommendation.
"If you can use a dietary supplement -- a natural product -- without any kind of adverse event it is really very useful, taking into consideration that patients with heart failure are treated with a lot of drugs," he said. "And to have something natural without side effects -- without interactions with other drugs -- is very important."
But, he said, "in my opinion, I think that to confirm this hypothesis it is necessary to have a real large-scale clinical trial."
CoQ10 is naturally produced in the body and is involved in energy production. It was first described in the 1950s and is now sold over the counter as a supplement.
Previous studies have shown that levels of CoQ10 are lower in cardiac biopsy samples from patients with more severe heart failure and that low plasma levels are associated with increased mortality in heart failure.
Smaller trials have demonstrated some benefits from CoQ10 in patients with heart failure, but none was sufficiently powered to demonstrate an effect on survival.
Mortensen's Q-SYMBIO study -- conducted at 17 centers in Australia, Austria, Denmark, Hungary, India, Malaysia, Poland, Slovakia, and Sweden -- was designed to address that issue. It included 420 patients with chronic heart failure and New York Heart Association class III or IV disease. Most had a reduced ejection fraction (average 31%). The average age of the patients was 62.3.
On the background of standard heart failure therapy, patients were randomized to receive either CoQ10 100 mg three times daily or placebo. The primary long-term endpoint was a composite of unplanned hospitalization due to worsening heart failure, cardiovascular death, urgent cardiac transplantation, or mechanical support at 2 years, but there was also a short-term assessment performed at 3 months.
After 3 months, the percentage of patients who had improvements in NYHA class was similar in the two groups (44% with CoQ10 versus 39% with placebo).
But after 2 years, the percentage who improved was greater in the CoQ10 group (58% versus 45%, P=0.047). Mortensen said that some patients improved from class IV to class I.
In addition to the primary endpoint of MACE, there were significant reductions in all-cause death (9% versus 17%, P=0.03) and cardiovascular death (8% versus 15%, P=0.02) in the CoQ10 group.
The benefits were consistent across various subgroups.
CoQ10 is available as an over-the-counter supplement, but Mortensen said that patients should not start taking it without discussing it with their doctors. He noted, however, that there is no evidence of interactions with established heart failure medications.
Maggioni agreed that the risks of adverse events or drug interactions are very small with CoQ10.
"I do not recommend [that patients] buy and take this kind of supplement, but I'm not worried if the patients are impressed by the results and want to use this kind of approach," he said. "It is surely safe."
Q-SYMBIO was funded by the International Coenzyme Q10 Association, Kaneka Corporation of Osaka, and Pharma Nord, which markets products containing coenzyme Q10.
Mortensen reported that he had no disclosures.
Primary source: Heart Failure Congress
Mortensen S, et al "The effects of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from the Q-SYMBIO study" HFC 2013; Abstract 440.
CoQ10 helps heart failure patients survive
by European Society of Cardiology
May 28, 2013
Taking coenzyme Q10 (CoQ10) supplements improved overall survival in a randomized placebo controlled study of patients with moderate to severe heart failure, reports the Q-SYMBIO trial. Furthermore, the investigator-initiated study, which is presented as an abstract at the Heart Failure 2013 meeting, also showed improvements in hospitalizations, NYHA class and adverse events for the group receiving CoQ10.
"The abstract represents the first study ever to have been adequately powered to show that CoQ10 has an effect on survival in heart failure patients. These results are guideline changing, making a strong case for CoQ10, a natural substance that's virtually without side effects, to be considered as part of the maintenance therapy for all patients with chronic heart failure," said Svend Aage Mortensen, the first author of the study, from the Heart Centre, Copenhagen University Hospital, Denmark. "CoQ10 (also known as ubiquinone) is a vitamin like substance, which is a component of the electron transport chain participating in aerobic cellular respiration, and generates energy in the form of ATP.
Furthermore, the capacity of this oil soluble substance to exist in a completely oxidized form and a completely reduced form enables it to perform antioxidant functions. First discovered in beef heart mitochondria by Frederick Crane in 1957, the chemical structure of CoQ10 was described by Karl Folkers in 1957.
The connection with heart failure has been known for some time, with an early study by Folkers and Mortensen finding that levels of CoQ10 in cardiac biopsy samples are inversely related to the severity of heart failure (PNAS, 1985, 82 pp901-904). Reduced levels in heart failure have been explained by a 'steal effect', where CoQ10 is also used for its antioxidant function to address oxidative stress in the failing heart, thereby diverting supplies away from the respiratory chain. Furthermore, Mortensen added, synthesis is known to be inhibited by statins (drugs commonly prescribed to heart failure patients), which are known to reduce serum levels of CoQ10 by up to 40 percent.
Altogether there have been around 15 double blind studies providing CoQ10 to heart failure patients, with endpoints including ejection fractions, changes in New York Heart Association (NYHA) classification, hospitalization, symptoms, and exercise capacity. The latest meta-analysis by Domnica Fotino, from Tulane University, New Orleans, which pooled data from 13 studies involving 395 heart failure patients, found that CoQ10 increased ejection fractions by an average of 3.67 percent (Am J Clin Nutr 2013, 2, 268-75). "Despite the large number of studies critics have remained skeptical about the benefits of CoQ10, largely because none of these studies had been sufficiently powered to look at overall survival," said Mortensen.
In the current study, 420 patients with NYHA Class III or IV receiving current pharmacologic therapy were randomly assigned to CoQ10 100 mg three times daily (n=202) or placebo (N=218). Patients were recruited from 17 centers in Denmark, Sweden, Austria, Slovakia, Poland, Hungary, India, Malaysia and Australia.
Results at three months showed there was a trend to reduced levels of NT-proBNP (used as a marker of the severity of heart failure) in the CoQ10group.
Result at two years show that the primary endpoint of major adverse cardiovascular event (MACE) was reached by 14 percent (29) of patients in the CoQ10 group versus 25 percent (55) of patients in the placebo group (P=0.003). Furthermore at two years, in comparison to placebo CoQ10 treated patients, had a significantly lower cardiovascular mortality (p=0.02), lower occurrence of hospitalizations (p=0.05), and showed greater improvements in functional NYHA class (p=0.047). With regard to all cause mortality at two year 9 percent (18 patients) had died in the CoQ10 group compared to 17 percent (36 patients) in the placebo group (p=0.01).
Intriguingly, fewer adverse events occurred among patients taking CoQ10 than those taking placebo (p=0.073).
CoQ10 supplements are available over the counter, with the lipid soluble form known to provide the best bioavailability. "Although CoQ10 is known to be remarkably safe, heart failure patients should consult their doctors before embarking on supplementation. To ensure no adverse interactions it would be a good idea to undertake an extra INR monitoring in patients taking anticoagulation therapy as with changes in diet or taking other new medications," he said. Waiting for the publication of this study, this kind of dietary supplement seems to provide promising results.