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Uric acid and stroke therapy

More research is needed

 

Portion of CT scan of a brain that has experienced acute ischemic stroke

Portion of CT scan of a brain that has experienced acute ischemic stroke

A Spanish research team has recently found that giving uric acid (UA) with intravenous thrombolytic therapy (tPA) to patients with acute ischemic stroke could help improve outcomes, particularly in women. Emergency Medicine Physician Dr. William J. Meurer talked with us about the study and its implications for stroke treatment and research.

Do the results of the Spanish study mean that hospitals will start supplementing clot-busting tPA with uric acid (UA) when they treat ischemic stroke patients?

No. The main trial didn’t find UA to work when given to everyone. The Spanish researchers have generated an interesting hypothesis by observing that it worked in women. There is not strong enough evidence yet to change practice, but it’s an interesting area for future research.

How did the team conduct the research?

The researchers reexamined the results of their Efficacy Study of Combined Treatment with Uric Acid and rtPA in Acute Ischemia Stroke (URICO-ICTUS) trial

They found that 42% of women treated with UA and 29% of women treated with placebo achieved an excellent outcome at 90 days. By comparison, 36% of men treated with UA and 34% of men treated with placebo achieved excellent outcomes.

The researchers concluded that UA treatment in addition to tPA caused excellent outcomes in women. But this wasn’t the main question they were seeking to answer in the trial, and was something that appeared after they looked at the data.

What do you think accounts for the better results in women?

Women have lower UA levels to begin with, so administering UA brought their levels up to a higher level. Other studies have found that both men and women with higher UA levels were more likely to do well after their strokes.

The real finding may be that people with lower UA levels are more likely to benefit from UA supplementation. If researchers conduct a larger trial that includes more men with lower UA levels, we may find that UA works in those men as well.

Why did they use uric acid?

After a stroke, the brain is injured. In addition to giving tPA to reduce the blockage in the artery, it is compelling to also try to give a medicine that can reduce the damage or protect the brain—a neuroprotectant. UA is in our metabolism, in our bodies, and is also a potent antioxidant—and potential neuroprotectant.

There have been a lot of promising studies looking at neuroprotection with many different agents, including other antioxidants, but when they have tried these in other large clinical trials in humans the new treatments weren’t any better.

Since uric acid is a naturally occurring substance in our body and seems to cause no harm, why not give it to everyone who is receiving tPA treatment?

A study that accurately measures side effects has to be pretty large. While UA is a natural part of our biochemistry, elevated levels can be seen with some diseases like gout and kidney failure. Also the women who did “well” in this study, actually only did about as well as patients who received tPA alone in the 1995 study that led to its adoption as a recommended treatment. Basically, this trial doesn’t allow us to precisely balance the potential benefits and harms of UA – so more research is needed.

What is the “take-away” for patients?

Before UA supplementation to tPA is considered a best practice approach in the treatment of stroke, there needs to be a research trial with a large number of participants.

If successful, some day UA supplementation could be an opportunity for personalized neuroprotection for acute stroke patients.

We at Michigan are part of an NIH-funded Stroke Network, and that is the sort of study that would be interesting to see.

Take the next steps

William_Meurer_MWilliam J. Meurer, M.D., MS, is Assistant Professor, U-M Department of Emergency Medicine and Department of Neurology. Dr. Meurer is interested in improving the acute care delivered for stroke patients in the emergency department by studying systems of care and barriers to delivering high-quality effective treatment. He also participates in research trials investigating new medications for use in acute ischemic stroke.

 

U of M Health logoThe University of Michigan Health System’s Comprehensive Stroke Program holds the official certification of Comprehensive Stroke Center, granted by the Joint Commission accrediting organization and recognized by the American Heart Association and American Stroke Association. Fewer than 100 other hospitals in the country have achieved this elite status.