Replies to post #61429 on Biotech Values

[iwfal]

For the reduction in heart attacks to have been seen so early, the benefit in these patients is as high, or higher, than the benefits seen in patients who start with high bad-cholesterol levels. The implication is remarkable: The main reason why blockbuster statins work may not be because they lower cholesterol, but because they reduce the inflammation that leads to heart attacks. "I think statins do work, but maybe not because they lower LDL," says Liao.


The bolded sentence is confirmation of what I have been saying (and last repeated a few weeks ago) - that statins work at least as much through CRP as cholesterol. Given the trial stats that they gave my guess is the efficacy is a LOT better than for high LDL patients. 45% reduction? 50% reduction?

What is amazing to me is how long it takes the medical establishment to figure out things like this. It was pretty obvious 5 years ago - and worthy of investigation 10 years ago.

PS Unlike Liao, I would not go so far as to say that statins don't provide some clinically meaningful benefit via lowering of LDL.

PPS It is a little disingenuous of me to claim credit for my prediction of two or three weeks ago (that the HR would be better than for moderate dose of statins in high LDL patients) since the very fact that the trial stopped early with 10,000 patient provided a clue. But regardless I have been saying for years on these boards that statins probably provided at least as much benefit through CRP as through cholesterol (although it might not be on this board - but on other boards such as AGIX). There really is a wealth of epidemiological data and analysis that supports this.

[apljack]

"Liao's own research has proved that statins have other biochemical effects than lowering cholesterol. Most important, they reduce the amount of an enzyme called Rho-kinase. That, in turn, dials back damaging inflammation in arteries. When Liao knocks down the level of Rho-kinase in rats, they don't get heart disease. And in new, still unpublished work, he has showed that simply reducing Rho-kinase in certain immune system cells is enough to reduce heart disease in rats."

Don't know if this is the same mechanism, or if there are other anti-inflammatory mechanisms at work as well with statins, but this may be the reason that there have been results pointing to modest protective effects of statins for Alzheimer's Disease.

regards

aj

[ghmm]

Crestor -

By chance would you know what the economics are for Shionogi (Is it a straight royalty/capped/etc.)?

The article said they had 218.6 million in royalties for first three quarters of '07.
http://www.forbes.com/markets/commodities/2008/04/01/shionogi-pharmaceutical-crestor-markets-equity-cx_vk_0401markets01.html

PS My interest in Shionogi is for another drug not yet approved :)

[DewDiligence]

Calcium Buildup Predicts Statin Benefit, Researchers Say

http://finance.yahoo.com/news/Heart-scans-show-most-likely-rc-1129178628.html?x=0&.v=85

›November 16, 2010
By Julie Steenhuysen

CHICAGO, Nov 16 (Reuters) - A heart scan that checks for hardening of the arteries is a better way to predict who will benefit from cholesterol-fighting statin drugs, U.S. researchers said on Tuesday in a finding that could reduce the number of people who take statins.

The researchers said the vast majority of heart attacks, strokes and deaths occur in people who have a measurable buildup of artery-hardening calcium in their blood vessels.

Only those patients are likely to need to take statins -- the world's top-selling prescribed drugs -- to protect them from an impending heart attack.

"Our results tell us that only those with calcium buildup in their arteries have a clear benefit from statin therapy," said Dr. Michael Blaha of Johns Hopkins University School of Medicine, who presented his findings at the American Heart Association meeting in Chicago.

The study vastly rolls back the number of people who should be treated with statins. Statins lower low-density lipoprotein or LDL, the bad kind of cholesterol, and a steady drumbeat of studies in recent years have expanded the potential pool of people who might benefit from taking them.

A major heart study two years ago dubbed Jupiter found giving the AstraZeneca (AZN) drug Crestor or rosuvastatin to people with average to low cholesterol but other heart risks cut the risk of heart attacks and strokes by half.

In that study, patients had low cholesterol but high levels of C-reactive protein, or CRP, a sign of inflammation that could mean a higher risk of heart attacks or strokes.

WHO WILL BENEFIT MOST FROM STATINS?

Blaha said his team had been working on ways to narrow down who will really benefit from taking a statin.

For their study, they identified a group of nearly 1,500 patients who were similar to the Jupiter population -- people with normal cholesterol and high CRP levels. They gave those patients a CT heart scan to check for calcium buildup and followed them for about five years.

They found most heart attacks -- 75 percent -- occurred in people with a high buildup of calcium in their arteries -- the top 25 percent in the study.

“We think we've shown it's very unlikely for someone with no coronary calcium to get any benefit in the near-term from taking statins,” Blaha said.

He said with the CRP test, doctors would have to treat 94 people to prevent one heart attack. But in the group with high calcium buildup in their arteries, doctors only need to treat 24 patients for one person to benefit.

Blaha said measuring calcium buildup in the arteries costs about $200 per scan and delivers a relatively low radiation dose -- about the same amount as 10 chest X-rays [the equivalent of ten chest X-rays doesn’t sound *that* low].

Dr. Robert Bonow of Northwestern University in Chicago and past president of the American Heart Association said the study confirmed earlier findings that calcium scores can help identify who will benefit from taking statins.

"You would not want to do this to everyone in the world," he said. "You would first do a risk assessment, and then target it to that group of people."

Coronary heart disease is the leading cause of death in the United States, killing one in five adults. Pfizer's Lipitor or atorvastatin has global sales of more than $10 billion while AstraZeneca's Crestor has global sales of more than $5 billion.‹

[DewDiligence]

Unorthodox thesis on LDL cholesterol from a professor at Texas A&M:

http://tamunews.tamu.edu/2011/05/04/%E2%80%98bad%E2%80%99-cholesterol-not-as-bad-as-people-think-shows-texas-am-study/

If the professor is correct, the muscle-weakness side effect of statin drugs makes perfect sense.

(Thanks to ‘Ian@SI’ on SI for this find.)

[DewDiligence]

“Once is happenstance, twice is coincidence, three times is enemy action, Mr. Bond.” *

1. Zetia showed no clinical benefit when added to Zocor in the ENHANCE study, despite raising HDL the way it was supposed to (#msg-25991228).

2. TriCor failed to show a statsig benefit when added to Zocor in the ACCORD study, despite lowering triglycerides and raising HDL the way it was supposed to (#msg-47808450).

3. Niaspan showed no clinical benefit when added to Zocor in the AIM-HIGH study, despite raising HDL the way it was supposed to (#msg-63617748).


We have enemy action.

*From Goldfinger.