Index Home About Blog
From: (Steve Harris
Date: 15 Oct 2004 15:45:18 -0700
Message-ID: <>

"Harvey R. Stone" <> wrote in message

> Ooooh, you make a very good point.   It is a point that includes the choice
> people make when they take a DMARD......   The choice of Vioxx  as a NSAID
> has been taken away for good reasons     and   it   is about Tomorrow   not
> about today's pain.   Its about tomorrows death.      We have people who are
> not in pain making choices for the people who are......    I am sorry to say
> that I am not smart enough to give an answer to that.
> Harv


Your government thinks it is.  Though to be fair, Vioxx was pulled off
the market by the maker, not the FDA. Those who claim some kind of
deception by the maker should keep this in mind.

Indeed, Vioxx increases the risk for heart attack and stroke by about
50%. You can do that easily by smoking a couple of cigarettes a day,
or by gaining 30 lbs. Or by being a couch potato.

The question of how much pain relief is worth a very small chance on
your life, is a good one.  People risk their lives to have plastic
surgery to correct the size of their noses or whatever. People risk
their lives to fly to Paris for vacation, or drive on the freeway to
grandma's for Thanksgiving dinner. Why shouldn't they be allowed to
take a risk to relieve constant pain?

The answer of course is: no particular reason. The Vioxx risk is just
something that hadn't been noted before. If it had, it's possible the
drug would have been approved anyway. After we get used to it, perhaps
it will be on the market again.

Anybody seen the recent TV ads for Enbrel?  You risk death from
infection, maybe an increased risk of developing lymphoma, and god
knows what else, all just to fix the heartbreak of psoriasis. Go


From: Steve Harris <>
Subject: Re: Merck & FDA fought over Vioxx label warning for 2 years - 
	while people died
Date: 30 Sep 2005 15:25:03 -0700
Message-ID: <>

Sharon Hope wrote:
> For those of you who may have missed it, earlier expert testimony in this
> trial, by the cardiologist involved in the invention of the first pacemaker,
> revealed that ONE DOSE of a COX-2 Inhibitor removes the body's natural
> anti-clotting protection for 85 HOURS.  It takes only a single dose to cause
> a clot that becomes a heart attack or a stroke.


Since that would have been in about 1960, this guy must be older than
dirt. Couldn't they do better?  In 1960 nobody had ever heard of
cyclooxygenase (COX), let alone selective COX isoform inhibition. All
of that is 90's research.

As for the idea that COX-2 inhibitors "removes the body's natural
anti-clotting protection for 85 HOURS," that is complete hooey. The
body has half a dozen anti-clotting inhibitors, and the one inhibited
by the COX-2 inhibitors is COX-2 derived prostacyclin. Which NOBODY had
any idea would be important in normal circumstances, in 2002. Through
the retrospectoscope, with further study, they're starting to make a
case that it might be important--- but that's KNOWING of the Vioxx
problems, and looking to try to figure out what was going on.

The reasonable conclusion from physiology is that COX-2 inhibitors
would leave COX-1 derived prostacyclin alone, thus preserving normal
anti-clotting protection. And indeed, COX-1 prostacyclin producton is
preserved. And it was indeed found that people taking COX-2 inhibitors
had NORMAL bleeding times, not abnormal ones, suggesting that nothing
abnormal was happening (bleeding times are prolonged by aspirin and
standard NSAIDS, which inhibit COX-2 in platelets and vessels). If
anything, it was found that Vioxx users on comadin had slight increases
in prothrombin time, indicating that (like other NSAIDS) the drug
should not be taken with coumadin unless a great deal of caution was
exercised. So the makers were triggered into thinking that the drug
either had no effect on bleeding, or perhaps was additive to coumadin
(probably via drug metabolism changes). There was NO suggestion of
abnormal clotting in any basic clotting study done with these drugs.

Now, post-Vioxx scandle, people are starting to look at COX-2 derived
prostacyclin, which is anticlotting prostacyclin made in vessels which
are under attack or inflammation or some other stress (it turns out
that vessels in FAT or under high blood pressure, are under stress).
And these vessels may need the extra COX-2 prostacyclin to stay open.
But who knew?

> Merck knew.
> Pfizer knew.
> The FDA knew.
> For TWO YEARS the patients did not know.

NO, this is baloney. None of these folks above "knew" anything that
would make them suspect that COX-2 prostacyclin did anything of
importance, which was good for anybody. That's what the lawyers are
claming, but they (and their paid cowboys) are looking through the
retrospectoscope also.

> In fact, there are 2 members of my immediate family who have had heart
> attacks this Calendar year.  Both took Celebrex.  Do you think that either
> one of their cardiologists even MENTIONED the fact that Celebrex could have
> caused the heart attack?  Do you think either cardiologist even ASKED when
> the last Celebrex pill was taken in relation to the heart attack?
> No?  You are correct.

They had no reason to think so. This odd bit of physiology is a result
of the pathology of inflammation, and is not seen in models of normal
animals, and normal tissues. It could only be discovered in the way
that it WAS discovered, which was to give the drug to animals with
vessel damage. But nobody thought of doing that. Not the FDA, not the
cardiologists, not the pharma critics. And not me either. And also not
Sharon.  Sharon thinks that the people who are paid to think of these
things, should have thought of them. Well, sorry, but that's not the
way nature works.

> So much for identifying adverse effects, let alone reporting them.

Indeed. Complicated universe it is.  You takes your pills and you takes
your chances. It's fairly easy to not take these chances. Just refuse
all pills. There you are.


From: Steve Harris <>
Subject: Re: Merck & FDA fought over Vioxx label warning for 2 years - 
	while people died
Date: 4 Oct 2005 16:01:06 -0700
Message-ID: <>

Sharon Hope wrote:
> "Merck's Vioxx Can Cause Heart Attack With One Dose, Expert Says "
> and
> "Merck's Vioxx May Cause Heart Attacks, Professor Says (Update1) "
> Excerpts:
> "``There's every reason to believe'' that a single dose ``can lead to an
> adverse response,'' Lucchesi, a pharmacology professor, told jurors in
> Atlantic City, New Jersey. ``I definitely think that Vioxx can cause a heart
> attack in the right person.'' "
> ...
> "Lucchesi testified for a second day that Merck ignored indications dating
> to 1997 that drugs like Vioxx block one of the body's natural defenses
> against blood clots. The company, based in Whitehouse Station, New Jersey,
> was ``forewarned on multiple occasions'' by researchers that Vioxx would
> increase clotting, he said.

In the test tube. Studies in normal humans showed nothing.

> Lucchesi also testified that after a 2000 study showed significant heart
> risks to Vioxx users, Merck told doctors and the public that Vioxx was
> safe. Lucchesi said that instead there was "an explosion" of reports by
> Merck executives and consultants saying that the other drug in that study,
> Naproxen, prevented heart attacks, not that Vioxx caused them.


Which was a reasonable conclusion at the time. Naproxen acts like
aspirin, and asprin is known to decrease heart attacks. But both
aspirin and Naproxen increase stomach bleeding, which Merck was trying
to prevent (stomach bleeding from non-selective NSAIDS like Naproxin
was known to be the single most serious side-effect of all drug classes
in terms of total deaths). Any drug which decreases heart attacks will
increase stomach bleeding to some extent. That is why Merck noted that
it was in a "no win" situation in suggesting doctors give aspirin to
Vioxx users (something I was doing at the time, for my heart patients).
Elderly patients die of clots in the brain or lungs or heart, if you do
nothing. If you try to prevent these, they bleed from the GI tract.
That's the story of medicine.

Nor can you have your cake and eat it, too. We now know something I
didn't know 3 years ago, which is that low-dose aspirin makes Vioxx
look like nonselective NSAIDS on the stomach, more or less removing ALL
of its protective effect. All of which suggests that (lack of) platelet
inhibition is part of the "bad effect" of Vioxx on the heart. Maybe
large part of it. Which means the drug company was, at least, partly
right in its thinking.

But DOW was right about silicone implants, too. That didn't keep them
from being sued into bankrupcy. They are no longer in the drug
business, and if this keeps up, nobody else will be either. We'll have
to have something like the national vaccine injury compensation act, to
settle all this. Otherwise, we're headed where we were with vaccines,
with all but 3 U.S. makers sued out of business, and the Feds having to
save the rest with some kind of tort reform.

The problem is the government never acts, until they actually have the
disaster. They'll let Merck go down the tubes meanwhile, just as they
let the medical division of Dow go down. Why not? Not until you can't
get pharmaceuticals in the US, or you can't get them at less than $5 or
$10 a pill, will something be done.


From: Steve Harris <>
Subject: Re: Merck & FDA fought over Vioxx label warning for 2 years - 
	while people died
Date: 4 Oct 2005 17:17:11 -0700
Message-ID: <>

Robert wrote:

> Every reason to believe based on science?
> The standard of proof in a criminal court room is "beyond a reasonable
> doubt".
> The standard of proof in a is civil court is "within a reasonable doubt" or
> if the scale is balanced on either side also known as "more reason than not"
> of such and such happening.


My face is red. The record needs correcting.

Now that I know who the professor in the Vioxx civil suit is (BR
Lucchesi), I can see why they picked him. Not a hired gun at all. Wups.
This suggestion that COX-2 drugs might be harmful with vascular injury
(where you'd need COX-2 prostacyclin as well as the normal COX-1
derived stuff) is actually *Lucchesi's baby.* This guy not only knows a
lot of about clotting, but the group at his lab is probably the first
in the open scientific literature to report on an experiment of type I
discussed as a hypothetical above: where you cause vascular injury (in
this case, to the coronaries of dogs, via electrical burn) and THEN
look at the effects of nonselective vs selective COX inhibition. With
an injured artery, you have the possiblity that *COX-2* derived
prostacyclin might be important. And HERE is where this is first
floated as a hypothesis to explain experimental data. I hadn't read
this physiology abstact-- it's one of thousands and thousands. It took
me some time even to sift it out of Lucchesi's work (he's an excellent
scientist and also quite prolific)

But we still have problems. As we all know, it's one thing to
hypothesize a mechanism as explanation for results in one experiment in
one animal model, and another to show that the mechanism is correct,
that it applies in general, and that it applies clinically to natural
disease problems in humans (who after all aren't getting their
coronaries electrically burned). How DO you show it in humans? Well,
you run a clinical study looking at vascular events in people on COX-2
inhibitors. Which was eventually done about this time. And the effects
were bad (I commend this to all those people suggesting animal research
tells us nothing).

So. Now, all ye pharma critics, riddle me this: On the basis of the dog
model below, and the single study below, would YOU (say you're
commissioner of the FDA) have removed Vioxx and Celebrex from the
market?  This is a nasty inductive question, wouldn't you say? And it's
a lot easier to carry out induction in hindsight.

Circulation. 2001 Aug 14;104(7):820-5.

Effects of selective cyclooxygenase-2 inhibition on vascular responses
and thrombosis in canine coronary arteries.

Hennan JK, Huang J, Barrett TD, Driscoll EM, Willens DE, Park AM,
Crofford LJ, Lucchesi BR.

University of Michigan Medical School, Department of Pharmacology, Ann
Arbor 48109-0632, USA.

BACKGROUND: Prostanoid synthesis via the action of cyclooxygenase-2
(COX-2) is a component of the inflammatory response. Prostacyclin, a
product of COX-2 in vascular endothelium, has important physiological
roles, such as increasing blood flow to injured tissues, reducing
leukocyte adherence, and inhibiting platelet aggregation. We examined the
possibility that selective COX-2 inhibition could suppress the protective
effects of prostacyclin, resulting in an alteration of the hemostatic
balance and vascular tone. METHODS AND RESULTS:  Circumflex coronary
artery thrombosis was induced in dogs by vascular electrolytic injury.
Orally administered celecoxib (COX-2 inhibition) or high-dose aspirin
(HDA) (COX-1 and COX-2 inhibition) did not alter time to occlusive
thrombus formation compared with controls (celecoxib 77.7+/-7.2 minutes,
HDA 72.0+/-18.5 minutes, control 93.0+/-21.8 minutes). Oral HDA with an
endothelial recovery period (HDA-ER) (COX-1 inhibition) produced a
significant increase in time to vessel occlusion (257.0+/-41.6 minutes).
The observed increase in time to occlusion was abolished when celecoxib
was administered to animals dosed with HDA-ER (80.7+/-20.6 minutes). The
vasomotor effect of endothelium-derived prostacyclin was examined by
monitoring coronary flow during intracoronary administration of
arachidonic acid or acetylcholine. In celecoxib-treated animals,
vasodilation in response to arachidonic acid was reduced significantly
compared with controls. CONCLUSIONS: The results indicate important
physiological roles for COX-2-derived prostacyclin and raise concerns
regarding an increased risk of acute vascular events in patients
receiving COX-2 inhibitors. The risk may be increased in individuals with
underlying inflammatory disorders, including coronary artery disease.

PMID: 11502709 [PubMed - indexed for MEDLINE]

From: Steve Harris <>
Subject: Re: A fatty acid found in milk may help control inflammatory diseases
Date: 19 Oct 2005 18:02:05 -0700
Message-ID: <> wrote:

Cute. Conjugated linoleic acid from milk is found to inhibit COX-2, at
just about the time we're finding out (via tort suits against Merck)
that mother nature does not like COX-2 inhibited in people with
arterial damage.

All of which might convince you that milk is for children, not the
middle-aged or elderly, lest it give them strokes or heart attacks. The
only problem with this idea, being that the epidemiology doesn't
support that. People who drink milk have fewer strokes and heart
attacks. So the story is undoubtedly more complex.

Moral: never believe simple just-so biochemistry unless it supports
epidemiology and controlled clinical trials. Nature is still too
complicated to dope out, de novo. A lesson Merck could have profitted


Index Home About Blog