No benefit from heart jab
An injection that can fool the body into healing heart failure “could save thousands of lives a year”, reported the Daily Mail. The technique involves an injection of specially treated blood cells that “trick the body into producing anti-inflammatory cells that heal the damaged heart”, the newspaper said.
The research behind these stories is an international randomised controlled trial which looked at the effects of modifying the immune system in people with chronic heart failure. The study found no overall evidence that the treatment worked. However, there was a slightly greater effect on people with mild symptoms and those who had no previous history of a heart attack. However, further studies will be needed to confirm this.
Where did the story come from?
Dr Guillermo Torre-Amione and colleagues from the Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy Investigators group, from research centres all over the world, carried out this research. The study was funded by Vasogen, the manufacturers of the device used for immunomodulation therapy. It was published in the peer-reviewed medical journal: The Lancet .
What kind of scientific study was this?
The study was a randomised controlled trial investigating the effects of immunomodulation therapy (a treatment which modifies the immune response) on health outcomes for people with chronic heart failure. Previous research suggested that exposing a sample of blood to “oxidative stress” and then re-injecting that blood back into the body causes the inflammatory response of the body to slow down and also stimulates an anti-inflammatory response – a process known as immunomodulation.
The 2,426 people included in this study came from 177 centres all over the world and all were receiving “optimum” therapy for heart failure, including drugs to help treat the condition and, in some cases, surgery. Participants randomly received immunomodulation therapy or a dummy therapy (placebo). During the immunomodulation therapy, blood was taken from the patient and exposed to “oxidative stress” (through exposure to an oxygen/ozone gas mixture for 20 minutes), then re-injected into the person; the dummy therapy procedure was the same, but instead of blood, a saline solution was injected. The similar procedures meant that the groups could not guess whether they were receiving treatment or not. In addition, the researchers who assessed the outcomes of the trial did not know either, i.e. the study was double-blind.
Two treatments were given on consecutive days, with another on day 14 and then at four week intervals for 22 weeks. After this time, researchers compared death rates (from any cause) plus hospitalisation for cardiovascular reasons between the groups. They also compared the time to any event (hospitalisation or death) between the groups.
The researchers were also interested in whether the treatment would have different effects on different groups of patients (different genders, with different histories of heart failure, etc), so they analysed the data accordingly.
What were the results of the study?
Overall, the researchers found there was no difference in the overall health outcomes (rate of death or hospitalisation from cardiovascular causes) between the groups. When they analysed the data using characteristics of the participants, they found that for two groups of patients the treatment reduced the risk of hospitalisation or death. These groups were patients with New York Heart Association (NYHA) class II symptoms of heart failure (i.e. slight to mild symptoms), who had a risk reduction of 39% and patients who had no previous history of a heart attack, in whom the risk was reduced by 26%.
What interpretations did the researchers draw from these results?
researchers say that “absence of benefit on the primary endpoint” was "disappointing", as there is a lot of evidence that inflammatory responses play a part in heart failure. They are cautious in their conclusions, saying that immunomodulation therapy “may” be beneficial to some people with heart failure, but that this needs to be tested in a larger trial.
What does the NHS Knowledge Service make of this study?
This well-conducted randomised controlled trial has disappointing overall results. The differences between the rate of death or hospitalisation for cardiovascular causes in the two groups was not statistically significant. The benefits that were seen in two particular patient groups will need to be confirmed by larger studies, as studies like this that perform a number of subgroup analyses carry a risk of false-positive findings.
The people in this study were all taking “optimum” treatment for their heart failure. This new treatment was not being tested as an alternative to these well-researched treatments, but in addition to them.
- Based on these results, it cannot be concluded that the injection is a proven treatment for people with heart failure. Any claim such is misleading.
Sir Muir Gray adds...
Single randomised controlled trials should only be the basis for action if they are very, very big and well designed; it will be interesting to see what other trials and a systematic review of all the trials concludes about this topic.
