EPO implicated in stroke study deaths

From the AP comes a report of a clinical study treating stroke subjects with EPO which found a higher death rate in the EPO group.  There will be a line in here about the link to sports doping with EPO; however looking at side effects in an elderly population suffering a stroke is far different than looking at side effects in an athletic population.

A blockbuster anemia drug made by a Johnson & Johnson company has been linked to the deaths of some patients in an experiment testing whether it could help stroke patients.with

J&J's Ortho Biotech unit said late Wednesday that it had learned of preliminary data from a study in which participants were being given its drug Procrit within six hours of suffering an ischemic stroke, in which an artery blockage limits the flow of blood and oxygen to the brain.

In the study, which was designed and initiated by a German scientist, more patients treated with Procrit died than in the comparison group receiving a placebo.

Johnson and Johnson released a PR statement, possibly to stem the criticism that pharmaceutic companies cover up deleterious side effects.

"Ortho Biotech chose to publicly communicate the results ... because of what we feel are potential safety implications," said company spokesman Mark Wolfe.

He said it is J&J's understanding that the idea behind the study "was based on data suggesting that patients suffering from stroke might benefit from epoetin therapy."

Epoetin alfa is the chemical name for the Procrit brand. The drug is also sold by another Johnson & Johnson unit under the name Eprex outside the United States, and Amgen Inc. sells it under the name Epogen in this country.

The drugs are all approved for treating anemia in cancer patients, people with kidney disease undergoing dialysis and some patients with HIV. They are not approved in any country for treating ischemic stroke patients. 

EPO, although frequently abused by athletes, is dangerous.

Strong warnings have been added to the package information for these drugs in recent years, as they have been linked to growth of existing tumors in some cancer patients and, at high doses, to heart complications and death.

The drugs work by stimulating production of oxygen-carrying red blood cells. Other versions, known as EPO, have been linked to doping by some athletes and banned because they boost endurance...

According to Wolfe, the study had been completed and preliminary data revealed a higher death rate.

Considering the report a few days ago of the ability of EPO to alter neuroanatomic structure, in conjunction with the information given above, this is a very interesting drug which appears to stimulate growth in a number of cell types.

Comments

[DyeLongJustice]

I really don't get why people suggest taking EPO. The theory behind EPO is that the athlete (generally an endurance athlete) can deliver more oxygen to his muscle cells by generating more red blood cells. The silly thing is that the limiting factor in muscle oxygen uptake for a healthy endurance (V02 max) is not the number of blood cells, nor is it the lungs. It is the number of mitochondria in the muscles cells that are available to do beta oxidation (use fat for energy rather than glycogen) so that less lactic acid is being produced from reduction of glucose (from the glycogen) as a result of the creation of a higher percentage of ATP from fats. In addition, and what makes the drug so dangerous, is the fact that it enhances the viscosity of the blood, increasing the work of the heart (and thus potentially decreasing performance). If you can imagine, this is like trying to drink a glass full of maple syrup with a straw rather than a glass full of water, with the straw being the arteries and the fluids being the blood. What an athlete should actually strive for (and a big response of the body to endurance exercise) is to decrease viscosity by adding blood plasma (the watery part) rather than hemoglobin (red blood cells). Thus, the heart could deliver the blood cells faster and easier to the muscle cells with a less viscous fluid and less resistance, rather than with a more viscous fluid and more resistance.

[StevieG]

They say sometimes, that the user's blood becomes thick like syrup, most likely this is an exagerration but I would believe there has been an abnormal amount of cyclists in Europe that have succumbed to heart problems and the like.

"Sermon and Marco Pantani - who also died from cardiac arrest, the investigating magistrate in Italy said - are the seventh and eighth cyclists to die from the condition in just over a year. Although there is no evidence directly linking the recent spate of fatalities to banned drug use, a similar cluster of deaths - mainly in the Low Countries - in the late 1980s and early 1990s is now held to have marked the arrival in cycling of the banned blood booster erythropoietin (EPO). "

http://www.guardian.co.uk/sport/2004/feb/16/cycling.cycling1

[DyeLongJustice]

When someone uses EPO and exercises for a long time, that is exactly what happens. You get a dual effect on increasing viscosity by exercising and using EPO because, as I stated before, EPO thickens the blood by adding more blood cells (hemoglobin) rather than the blood plasma (watery part). If you combine this with dehydration from a sport such as cycling (dehydration lowers the amount of blood plasma), you get a sticky mix of a lot of red blood cells, and not enough plasma. When this happens, the heart must not only work hard to supply blood to the limbs in use, but also must overcome greater peripheral resistance from the vascular system. This in turn increases the hearts workload, so now the heart must consume more oxygen, the lungs must work harder (thus the muscles of respiration need more blood too), and as you can see the effect cascades. Eventually, the heart becomes way too overworked, and the athlete's heart becomes endangered.

[DyeLongJustice]

I just looked up the numbers, and if you have a normal Packed Cell Volume (~45% red blood cells versus plasma), the viscosity is 3 times that of water, so the heart must push three times harder on the blood to get the same flow of blood as if it was water. If the PCV only goes up 15%, the viscosity increases 5-6 times. Thus, adding blood cells only exponentially increases the viscosity and heart workload.

[Outsourcing Copenhagen]

your blog post is very informative, thanks for sharing it.