Re: Lawsuit questions need for Lipitor: The ASCOT trial's 2000 women


David Rind wrote:
> fresh~horses wrote:
> > The study refererenced in Roni Rabin's Newsday article at the head of
> > this thread ("...2000 women...") is ASCOT, published in Lancet in April
> > 2003.
> >
> > And here is an snippet regarding the lawsuit, with the lawsuit website
> > linked below.
> >
> > David if you want the table for the ASCOT trial I can e-mail it as
> > attachment.
> >
> > MEM do you have a workable address? Anyone wants it say so on group,
> > please. Despammed is defunct.
> >
> >
> > Zee
> >
> > "Although Lipitor has been on the market since 1996,
> > it wasn't approved for the prevention of heart attacks
> > until 2004. The FDA approved it for this because a
> > large study (called the "ASCOT" study) showed that there
> > was a reduction in heart attacks overall for the
> > approximately 10,000 patients in that study. However, the
> > FDA looked at this study as a whole, rather than
> > looking at the different types of patients in the study. In
> > fact, the women in that study who had no prior history
> > of heart disease who took Lipitor actually had 10%
> > more heart attacks than the 1,000 women taking a placebo.
> > Despite the fact that the FDA approved Lipitor for
> > prevention of heart attacks, there is still no reliable
> > medical evidence that Lipitor or any other statin is
> > effective at preventing heart attacks for women and
> > people over 65, who have no history of heart disease."
>
> Okay, it probably should have occurred to me that this was from ASCOT-LLA.
>
> First a philosophical comment about looking at subgroup analyses: they
> are usually a bad idea. This applies both in negative studies where
> pharmaceutical companies try to find a subgroup the drug worked in, and
> positive studies where doubters try to find a subgroup the drug failed in.
>
> In general, a therapy that works in one group has simlar relative
> effects in all groups. There are exceptions, but this should be the
> default expectation. If I show you a study demonstrating that statins
> work in people, and you are short, left-handed, and have brown hair,
> it's not generally reasonable to expect that I prove to you that the
> study also showed benefit in short, left-handed, brunettes. In the
> absence of strong evidence to the contrary, the relative benefit should
> be assumed to be the same as in everyone else. By chance alone, when we
> start performing subset analyses we will find groups where a proven
> treatment appears not to work and where a useless treatment appears to work.
>
> The default assumption, in the absence of strong evidence to the
> contrary, should be that statins (and blood pressure medicines, and
> antibiotics, and vitamins) have the same relative effects in men and
> women. Note, by the way, that this does not apply to differences in
> absolute benefit -- women, on average, are at lower risk for coronary
> heart disease than men, and so, on average, will get less absolute
> benefit from statins than men. But we should expect that women have the
> same relative benefit and that a woman who happened to be at baseline
> high risk would have the same absolute benefit as a man with the same
> baseline high risk.
>
> This should even be the default assumption when a subgroup analysis
> appears to show a statistically different effect in one subgroup from
> another -- the likelihood of this being due to chance remains high if
> the study performed lots of subgroup analyses. However, this was not the
> case in ASCOT. ASCOT found no statistically significant difference in
> the effect of statins in men and women and so looking at the individual
> subgroups is particularly suspect.
>
> Second, ASCOT actually provided almost no data at all on the effects of
> statins in women. The comment quoted above about a 10% increase in
> events in women is just the sort of disingenous language that one might
> expect from a pharmaceutical company trashing a competitor's product or
> from someone with a stake in the outcome ignoring the actual evidence
> (not that one could ever imagine a litigator doing such a thing).
>
> There were thirty-six primary outcome events in women in ASCOT --
> THIRTY-SIX! Nineteen occurred in women taking atorvastatin and 17 in
> women taking placebo. Those two events out of 17 represent the 10%
> increase the article is apparently referring to. To say that this was
> not statistically significant and that the confidence intervals were
> wide doesn't begin to address how silly it is to make any conclusions
> about a differential effect of statins in men and women based on ASCOT.
>
> We have evidence from other studies with more events, by the way, that
> statins really do seem to have the same relative benefits in men and
> women just as we would have expected had we never bothered to look.
>
> So, when the author of the quote above writes that the FDA "looked at
> the study as a whole, rather than looking at the different types of
> patients in the study", the response should be that indeed that's what
> the FDA did, and they did exactly the right thing.
>
> --
> David Rind
> drind@xxxxxxxxxxxxxxxxxxxxx




I was told the single study upon which the 2001 guidelines used for
evidence that statins are beneficial in primary prevention of heart
disease in women was the AFCAPS/TexCAPS. In that study, there only 20
(TWENTY) cardiac events in women, yet it was the evidence for millions
of women being put on statins.

For comparison; in the ASCOT study the women who took statins developed
a *nonsignificant* 10% increase in cardiac events.

And as you probably remember but I'll post again because MEM may not
have seen this, Therapuetics Initiative found statins did not have
benefit for women for primary prevention:

http://www.ti.ubc.ca/pages/letter48.htm#comment
A question to us about Letter #48: What is the evidence of benefit for
primary prevention in women?

"There were 10,990 women in the primary prevention trials (28% of the
total). Only coronary events were reported for women, but when these
were pooled they were not reduced by statin therapy, RR 0.98
[0.85-1.12]. Thus the coronary benefit in primary prevention trials
appears to be limited to men, RR 0.74 [0.68-0.81], ARR 2.0%, NNT 50 for
3 to 5 years."

.

Relevant Pages

  • Re: Lawsuit questions need for Lipitor: The ASCOT trials 2000 women
    ... In that study, there only 20 cardiac events in women, yet it was the evidence for millions of women being put on statins. ... It would therefore be rather surprising for them to have differential relative benefits by gender in primary prevention. ... I think the burden of proof is on those who would claim that there is such a differential relative benefit in primary prevention. ...
    (sci.med.cardiology)
  • Re: Bad lab reports
    ... The last major revision of the US guidelines, in 2001,1 increased the number of Americans for whom statins are recommended from 13 million to 36 million, most of whom do not yet have but are estimated to be at moderately elevated risk of developing coronary heart disease.In support of statin therapy for the primary prevention of this disease in women and people aged over 65 years, the guidelines cite seven and nine randomised trials, respectively. ... Yet not one of the studies provides such evidence.For adults aged between 30 and 80 years old who already have occlusive vascular disease, statins confer a total and cardiovascular mortality benefit and are not controversial.The controversy involves this question: which people without evident occlusive vascular disease (true primary prevention) should be offered statins? ... In our experience, many men presented with this evidence do not choose to take a statin, especially when informed of the potential benefits of lifestyle modification on cardiovascular risk and overall health.8 This approach, based on the best available evidence in the appropriate population, would lead to statins being used by a much smaller proportion of the overall population than recommended by any of the guidelines. ...
    (alt.support.diabetes)
  • Re: Bad lab reports
    ... number of Americans for whom statins are recommended from 13 million to ... primary prevention) should be offered statins? ... many men presented with this evidence do not ... Thanks for finding the original article. ...
    (alt.support.diabetes)
  • Re: Bad lab reports
    ... Yet not one of the studies provides such evidence.For adults aged between 30 and 80 years old who already have occlusive vascular disease, statins confer a total and cardiovascular mortality benefit and are not controversial.The controversy involves this question: which people without evident occlusive vascular disease (true primary prevention) should be offered statins? ... In our experience, many men presented with this evidence do not choose to take a statin, especially when informed of the potential benefits of lifestyle modification on cardiovascular risk and overall health.8 This approach, based on the best available evidence in the appropriate population, would lead to statins being used by a much smaller proportion of the overall population than recommended by any of the guidelines. ... Thanks for finding the original article. ...
    (alt.support.diabetes)
  • Re: Lawsuit questions need for Lipitor: The ASCOT trials 2000 women
    ... >> it wasn't approved for the prevention of heart attacks ... >> FDA looked at this study as a whole, ... > First a philosophical comment about looking at subgroup analyses: ... If I show you a study demonstrating that statins ...
    (sci.med.cardiology)