Sunday, April 8, 2007

Warfarin Use in Men Defended by UW Monkey Vivisector

UW Vivisector Debunks Human Epidemiological Warning with Monkey Data.

J Bone Miner Res. 2007 Feb 12; [Epub ahead of print]

Vitamin K Deficiency From Long-term Warfarin Anticoagulation Does Not Alter Skeletal Status in Male Rhesus Monkeys.
Binkley N, Krueger D, Engelke J, Suttie J.

Vitamin K (K) inadequacy may cause bone loss. Thus, K deficiency induced by anticoagulants (e.g., warfarin) may be an osteoporosis risk factor. The skeletal impact of long-term warfarin anticoagulation was evaluated in male monkeys. No effect on bone density or markers of skeletal turnover was observed. This study suggests that warfarin-induced K deficiency does not have skeletal effects.
Ok. Let me be clear from the start: I’m not claiming that Neil Binkley et al. are shills for the University of Wisconsin; I’m just saying that it looks like they are.

Just the facts mam, just the facts:

This is what the (always accurate) online encyclopedia Wikipedia has to say (or did say on April 8, 2007)about warfarin.

The identity of the anticoagulant substance in moldy sweet clover remained a mystery until 1940 when Karl Paul Link and his student Harold Campbell, chemists working at the University of Wisconsin, determined that it was the coumarin derivative 4-hydroxycoumarin. Over the next few years, numerous similar chemicals were found to have the same anticoagulant properties. The first of these to be widely commercialized was dicoumarol, patented in 1941. Link continued working on developing more potent coumarin-based anticoagulants for use as rodent poisons, resulting in warfarin in 1948. (The name warfarin stems from the acronym WARF, for Wisconsin Alumni Research Foundation + the ending -arin indicating its link with coumarin.) Warfarin was first registered for use as a rodenticide in the US in 1952; although it was developed by Link, the WARF financially supported the research and was granted the patent.

After an incident in 1951, where a naval enlisted man unsuccessfully attempted suicide with warfarin and recovered fully, studies began in the use of warfarin as a therapeutic anticoagulant. It was found to be generally superior to dicoumarol, and in 1954 was approved for medical use in humans. A famous early patient prescribed warfarin was Dwight Eisenhower, president of the USA, subsequent to his heart attack in 1955.
So, the patent to warfarin is owned by WARF.

In 2006, researchers at Washington University in St. Louis reported:

"We did a retrospective study of Medicare records for about 15,000 patients hospitalized with atrial fibrillation, and we identified fractures related to osteoporosis," says lead author Brian Gage, M.D., associate professor of medicine and medical director of Barnes-Jewish Hospital's Blood Thinner Clinic. "Our analysis showed that long-term use of warfarin—longer than one year— led to a 25 percent increase in the incidence of fracture."
So, compare the studies’ designs and results:

Epidemiological study of 15,000 humans by researchers at the Washington University in St. Louis: “[M]en in the study who took warfarin for more than a year had a 63 percent higher incidence of fracture than men who did not take the blood thinner.”

Laboratory study of 20 adult male rhesus monkeys by researchers at the University of Wisconsin: “Long-term W[arfarin] therapy does not have adverse skeletal consequences in primates with high intakes of calcium and vitamin D.”

The data from the Wisconsin study was gathered in the late 1990s. It’s just a coincidence, I’m sure, that researchers from the institution holding the patent to warfarin chose to publish their report: “Long-term Warfarin Anticoagulation Does Not Alter Skeletal Status in Male Rhesus Monkeys” on the heals of a study by researchers at a different institution suggesting that long-term use of warfarin may impose a significant risk of bone fracture in men.

I’m sure this is all just a coincidence, after all, the UW, Madison researchers were clear: “All authors have no conflicts of interest relevant to this work.”

One final thing. One of the monkeys used in the Wisconsin study was monkey Rhao45. At the beginning of the study and at its end, Rhao45 underwent biopsies of a rib and the iliac crest (at the top of his hip bone.) (He was eventually killed after more experimentation on his brain and being repeatedly rectally infected with SIV, but that’s another story.)

Following the second biopsy, the wound over his hip developed full-thickness skin necrosis and took over a month and a half to really begin to heal. But hey, at least we know that, unlike men, male monkeys might not be prone to bone loss due to long-term use of warfarin. Yipee.

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