Re: Do drugs {including statins} and procedures benefit women and men equally?

Jim Chinnis <jchinnis@xxxxxxxxxxxxxxxx> wrote in part:

bigvince <Vince.Miraglia@xxxxxxxxx> wrote in part:

Heres a little more From BMJ 2007;334:983 (12 May), doi:10.1136/bmj.
39202.397488.AD excerpts


This is closer to what I was looking for. let me intersperse a few comments.

"Should women be offered cholesterol lowering drugs to prevent
cardiovascular disease? No
Malcolm Kendrick, general practitioner

......Lack of benefits
The Scandinavian simvastatin survival study found the biggest effects
of all statin trials-in men. However, what is less publicised is that,
overall, three more women died in the statin arm than in the placebo
arm.5

There was a follow-up analysis/study of deaths during the five years
following the 5-year treatment period in the (1994?) 4S study. A big
difficulty in getting statistically significant mortality results,
particularly on subgroups, is that the period covered by the study isn't
long enough either for the needed statistical power or to see what the
delayed effects of treatment are. The reduction in mortality was 15% over
that period, though as far as I can tell after a quick search, no
sex-specific data have been reported. http://tinyurl.com/ysojt9

The more recent heart protection study was hailed as a major
success for men and women, but despite the hype there was no effect on
overall mortality in women.6

I will try to track down the sex-specific results cited in the BMJ
editorial. Certainly the overall study found a large drop in all-cause
mortality. http://tinyurl.com/29awl4

In addition, the 2005 HPS report on subgroup data I *thought* had shown
overall mortality benefits to women. From the abstract: "The proportional
reduction in the vascular mortality rate was about one-sixth in each
subcategory of participant studied, including: men and women; under and over
70 years at entry; and total cholesterol below 5.0 mmol/L or LDL cholesterol
below 3.0 mmol/L. No significant excess of non-vascular mortality was
observed in any subcategory of participant ..., and there was no significant
excess in any particular cause of non-vascular mortality. Cancer incidence
rates were similar in the two groups, both overall and in particular
subcategories of participant, as well as at particular primary sites."
http://tinyurl.com/22dj37

I have a copy of the HPS study reports and will read them over later and
comment in this thread again. Certainly the HPS study was large enough to
support a comparison of overall mortality between men and women, though a
longer term study would always be more meaningful.

Vince, do you have a copy of the Kendrick paper? Can you tell me what he is
referring to as citation # 6?

In the studies of primary prevention neither total mortality nor
serious adverse events have been reduced.7 A meta-analysis published
in the Lancet found that statins even failed to reduce coronary heart
disease events in women.8 Of greater concern is that a further meta-
analysis of statins in primary prevention suggested that overall
mortality may actually be increased by 1% over 10 years (in both men
and women).9

Irrelevant. The topic is "Women With Heart Conditions Might Need Different
Treatments Than Men With Similar Conditions, Doctors Say." The topic is NOT
about primary prevention.

Sex differences
Perhaps it should not be a surprise that men and women respond
differently to statins. In most countries cardiovascular disease
strikes men at a much earlier age. Also, the relation of risk to
cholesterol concentrations is not consistent. To quote from a major
conference held in 1992 that looked at the data from 523 737 men and
124 814 women from 19 studies and trials: "Many findings for women
were discrepant from those for men. Of particular importance in women
was considered to be the essentially flat relation of TC [total
cholesterol] to total mortality, total CVD [cardiovascular disease],
and total cancer."10

What creates this difference is a matter of debate. However, when we
know that such differences exist, and the results from the statin
trials point to highly divergent end points, it seems inappropriate
that the guidelines (and thus the advice on using statins) remain
exactly the same for men and women. This seems to run directly
contrary to the concept of evidence based medicine.

I have no disagreement with the above two paragraphs. The issue to me is
whether women at the same risk of cardiovascular events benefit less from
statins than do men. I think the question of risk assessment is a very real
one and that different models are probably needed for men and women.

I just don't think that studies have shown less response to statins in women
with heart disease who are at comparable levels of risk as men in the same
studies.

The 4s study and the HPS lack of mortality benefit in women seem
compelling and consistant with the other data.

See my comments above.

I found the all-cause mortality data subdivided by sex. Take a look at
figure 8 in the following report: http://tinyurl.com/234f2k

The data are:

Simvastatin treatment group:
Deaths
Males 1102/7727 = 14.3%
Females 226/2542 = 8.9%

Placebo group:
Deaths
Males 1245/7727 = 16.1%
Females 262/2540 =10.3%

So, according to the actual published data, women--even though they were at
a much lower level of risk than the men in the study--achieved a 1.4%
reduction in total mortality compared with men's reduction of 1.8%.

I think it's clear that women given the same lipid etc. criteria as men will
be at lower risk. I think it's clear also that the primary benefit of the
statin is in reducing cardiovascular mortality (and morbidity), and that the
slightly lower benefit shown to women in this enormous trial is due to their
lower level of absolute risk rather than a lack of response to simvastatin.
--
Jim Chinnis Warrenton, Virginia, USA
.

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