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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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In the Pipeline

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June 14, 2010

Angiotensin Receptor Blockers and Cancer: For Real?

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Posted by Derek

Well, this could be nothing, or it could be big trouble: there's a report out that taking the angiotensin antagonists (the various "sartans") might be linked to increase risk of cancer. A meta-analysis of several large trials, reported in Lancet Oncology, patients in the treatment groups showed a 7.2% incidence of new cancer diagnoses, versus 6% for the control groups. These are large sample sizes, so that difference has a p-value of 0.016.

The authors wisely refuse to take the data any further, and call for more investigation, which certainly seems warranted. The whole renin-angiotensin system is certainly involved in angiogenesis, and thus could very plausibly have effects in oncology. But the surprising thing is that there's evidence that blockade of the receptors could actually cut down on tumor formation, too. If you'd taken a survey last week, you'd probably have gotten a lot of people to bet that these drugs would actually have a protective effect.

So what's going on? It's going to be quite a while before we find out. But an awful lot of people take these drugs, and now they're all wondering what to do. . .

Comments (9) + TrackBacks (0) | Category: Cancer | Cardiovascular Disease


1. chucky on June 14, 2010 11:22 AM writes...

Most likely noise, meta-analyses such as these mostly worthless....

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2. hypnos on June 14, 2010 12:07 PM writes...

Perhapt not too surprising, the vendor of the drug strongly disagrees with the results:

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3. anchor on June 14, 2010 12:49 PM writes...

Derek: When people live longer, we all do get some type of cancer anyway. Did the study considered this preposition?

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4. LeeH on June 14, 2010 12:56 PM writes...

If it's true, I guess you'll have to do some sort of benefit/risk analysis. If it's a wash, then we're back to low tech solutions for blood pressure.

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5. partial agonist on June 14, 2010 4:50 PM writes...

Probably they will be protective vs. some genotypes of cancer while conferring a measurable added risk vs. other kinds of cancer, with the net sum being non-zero. So I guess it depends upon whether you are otherwise in a risk group for a particular type of cancer. sort of like the drugs affecting estrogen, a mixed bag.

For example if all of the added risk is in testicular and prostate cancer, maybe you are concerned about giving these to men, unless the benefit is huge and the patient can be regularly screened for those cancers.

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6. NHR_GUY on June 14, 2010 9:32 PM writes...

I am familiar with ARBs and Telmisartan in particular. Telmisartan is well known to have a measurable amount of (in vitro and in vivo) activity at PPAR gamma, an NHR used for insulin sensitization. PPAR gamma is the same biological target for the TZD's such as rosiglitazone and pioglitazone. I wonder if the acitivity at PPAR gamma is what could be driving this slight increase in cancer risk. Two points, the types of cancer being reported have been linked to PPAR gamma though the marketed drugs are ostensibly clean. From my experience, the other ARB's have no measurable PPAR gamma activity and FTA, did not show an increased cancer risk.

and a p.s.
the two year carc studies mandated by the FDA for all new PPAR's in development was the last nail in the coffin for big pharma working on PPAR's.

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7. alex on June 15, 2010 3:49 AM writes...

Surprisingly, its not only cancer. Meanwhile the FDA is conducting a safety review of olmesartan (Daiichi Sankyo) after determining that diabetic patients taking the drug in two completed phase 3 trials may have had an excess risk of cardiovascular death.

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8. Kent G. Budge on June 15, 2010 10:35 AM writes...

"the two year carc studies mandated by the FDA for all new PPAR's in development was the last nail in the coffin for big pharma working on PPAR's."

Given that pioglitazone is associated with a *decrease* in cardiovascular risk, I find this profoundly regrettable. There could be considerable value in figuring out why some PPAR agonists increase cardiovascular risk and others decrease it.

My suspicion is that there are subtle differences in how much a given glitazone sensitizes different tissues to insulin. Perhaps rosiglitazone sensitizes arterial walls to insulin more than it sensitizes skeletal muscle, causing the arterial walls to take up too much glucose, while pioglitazone sensitizes skeletal muscles a bit more and avoids this effect. But it looks like we'll never know now.

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9. Erock on June 2, 2011 12:29 PM writes...

Looks like the FDA can out-meta-analyze the Lancet. Nothing to see here... move along...

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