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

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

On Sep 12, 10:38 am, Jim Chinnis <jchin...@xxxxxxxxxxxxxxxx> wrote:
bigvince <Vince.Mirag...@xxxxxxxxx> wrote in part:



On Sep 11, 4:02 pm, Jim Chinnis <jchin...@xxxxxxxxxxxxxxxx> wrote:
bigvince <Vince.Mirag...@xxxxxxxxx> wrote in part:

ASCOT-LLA (2003)
ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering
Arm) was designed to assess the benefits of atorvastatin (Lipitor)
versus a placebo in patients who had high blood pressure with average
or lower-than-average cholesterol concentrations and at least three
other cardiovascular risk factors.48 The trial was originally planned
for five years but was stopped after a median follow-up of 3.3 years
because of a significant reduction in cardiac events. Lipitor did
reduce total myocardial infarction and total stroke; however, total
mortality was not significantly reduced. In fact, women were worse off
with treatment. The trial report stated that total serious adverse
events "did not differ between
patients assigned atorvastatin or placebo," but did not supply the
actual numbers of serious events.

This was for primary prevention.

Jim heres my original comment

"As some studies have suggested that statins also have even less
value
in women does the one size fits all approach in the ATP guidelines
need rethinking. '

Where in that comment do you see a restiction on studys on primary
prevention . The Ascott study is relavent to my comment .Thanks
Vince

Your original POST was a news story about women with heart disease ("clogged
arteries). You took a news story about how women with clogged arteries might
need different procedures than men and ran with it.

The news item from your post:

*********************
Women With Heart Conditions Might Need Different Treatments Than Men
With Similar Conditions, Doctors Sayhttp://www.medicalnewstoday.com/articles/81448.php

Researchers at the annual meeting of the European Society of
Cardiology in Vienna, Austria, on Monday said that women with heart
conditions might need different treatments than men and that the issue
needs to be studied further, the AP/Hartford Courant reports.

The American College of Cardiology last month revised its treatment
guidelines to recommend that doctors be more cautious about subjecting
women at low risk of heart disease to invasive procedures. According
to the AP/Courant, an example of increased caution would be a
physician waiting to see if further symptoms develop in a woman with a
clogged artery rather than performing an angioplasty, which involves
inflating a tiny balloon in the clogged vessel. Guidelines in Europe
for treating heart disease are usually the same for men and women, the
AP/Courant reports.

Eva Swahn of the department of cardiology at University Hospital in
Linkoping, Sweden, on Monday presented a study of 184 women with heart
conditions. The women were divided into two equal groups: one in which
the women underwent an invasive procedure -- such as a coronary bypass
surgery or an angioplasty -- and a second group in which women waited
until further symptoms developed. Eight of the women who underwent an
invasive procedure died after one year, compared with one death in the
group of women who waited for further diagnosis."..........

As some studies have suggested that statins also have even less value
in women does the one size fits all approach in the ATP guidelines
need rethinking.
--
Jim Chinnis Warrenton, Virginia, USA

I posted the link and assumed you read the article. The reference to
the ATP guidelines I thought was clear enough.from the piece I posted

According to the AP/Courant, physicians are not sure what accounts
for the differences. Women typically have smaller hearts and vessels,
which can complicate procedures that require instruments such as
catheters. Women also tend to have more side effects from medicines,
and hormones also might be factors. In addition, women are usually
about 10 years older than men when they develop heart conditions, so
other health problems linked to old age could also increase their risk
of heart surgery complications, the AP/Courant reports.

Comments
"There is a big question mark over why this is happening," Swahn --
who consults for some pharmaceutical companies and is writing a book
for AstraZeneca -- said, adding, "We want there to be equality between
the genders, but that doesn't mean that women and men should get the
same treatment." Swahn's study was part of a larger study funded by
pharmaceutical companies Sanofi-Aventis and GlaxoSmithKline.

Some experts said no definitive conclusions can be taken from Swahn's
study but added that gender differences in heart treatments should be
studied further. "We have had hints in the past that women don't
respond to treatment in exactly the same way as men," Christopher
Cannon, an associate professor of medicine at Harvard University and
spokesperson for A'CC, said. Cannon was not associated with Swahn's
research (Cheng, AP/Hartford Courant, 9/3).

In either case significant reduction in mortality has never been shown
for women in any study or meta analysis . That holds true in women
across the board with or without CVD. If you have a study or meta
analysis that disproves that statement please post it. And perhaps you
could comment on the Ascott study another trail where women fared less
well on treatment
Thanks Vince

Vince, I think you start from a position that I can't disagree with:

"No randomized controlled trial has shown an all-cause mortality reduction
in women specifically at a p-level less than 0.05."

You then drop mentioning the requirement for your magic number 0.05.

You then begin to behave as if the absence of such a result when such a
result obtains for the (larger) male subgroup indicates that women benefit
less than men, which is just not a justifiable conclusion. Your statistical
logic is wrong. The error you make is a common one.

Nevertheless, I'm happy to read/reread these studies.

Here is the the abstract describing the design of the ASCOT study:

"J Hypertens. 2001 Jun;19(6):1139-47. Links
Rationale, design, methods and baseline demography of participants of the
Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.Sever PS,
Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen
SE, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J.
Imperial College School of Medicine, London, UK. p.sever@xxxxxxxx

"OBJECTIVE: To test the primary hypothesis that a newer antihypertensive
treatment regimen (calcium channel blocker +/- an angiotensin converting
enzyme inhibitor) is more effective than an older regimen (beta-blocker +/-
a diuretic) in the primary prevention of coronary heart disease (CHD). To
test a second primary hypothesis that a statin compared with placebo will
further protect against CHD endpoints in hypertensive subjects with a total
cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open,
blinded endpoint trial with a double-blinded 2 x 2 factorial component.
SETTING: Patients were recruited mainly from general practices. PATIENTS:
Men and women aged 40-79 were eligible if their blood pressure was > or =
160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140
mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization.
INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/-
perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide
(1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure
of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total
cholesterol of < or = 6.5 mmol/l were further randomized to receive either
atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal
myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS:
19 342 men and women were initially randomized, of these 10297 were also
randomized into the lipid-lowering limb. All patients had three or more
additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power
(at the 5% level) to detect a relative difference of 20% in CHD endpoints
between the calcium channel blocker-based regimen and the beta-blocker-based
regimen. The lipid-lowering limb of the study has 90% power at the 1% level
to detect a relative difference of 30% in CHD endpoints between groups."

Notice that all-cause mortality was not the endpoint. Notice also that the
patients included were not heart disease patients. It was a primary
prevention study that addressed the question of whether atorvastatin would
reduce the combined toll of non-fatal MIs and deaths attributable to heart
disease. Note also that the study was not powered to study differences
between the sexes. Finally note the unusual selection of
patients--hypertensives with low to normal lipids.

Regardless, let's look at the study results. Here is the abstract of the
main report:

" Lancet. 2003 Apr 5;361(9364):1149-58.
Prevention of coronary and stroke events with atorvastatin in hypertensive
patients who have average or lower-than-average cholesterol concentrations,
in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm
(ASCOT-LLA): a multicentre randomised controlled trial.Sever PS, Dahlöf B,
Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE,
Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J;
ASCOT investigators.
Imperial College, London, UK.

BACKGROUND: The lowering of cholesterol concentrations in individuals at
high risk of cardiovascular disease improves outcome. No study, however, has
assessed benefits of cholesterol lowering in the primary prevention of
coronary heart disease (CHD) in hypertensive patients who are not
conventionally deemed dyslipidaemic. METHODS: Of 19342 hypertensive patients
(aged 40-79 years with at least three other cardiovascular risk factors)
randomised to one of two antihypertensive regimens in the Anglo-Scandinavian
Cardiac Outcomes Trial, 10305 with non-fasting total cholesterol
concentrations 6.5 mmol/L or less were randomly assigned additional
atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm
of the study. We planned follow-up for an average of 5 years, the primary
endpoint being non-fatal myocardial infarction and fatal CHD. Data were
analysed by intention to treat. FINDINGS: Treatment was stopped after a
median follow-up of 3.3 years. By that time, 100 primary events had occurred
in the atorvastatin group compared with 154 events in the placebo group
(hazard ratio 0.64 [95% CI 0.50-0.83], p=0.0005). This benefit emerged in
the first year of follow-up. There was no significant heterogeneity among
prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121
placebo, 0.73 [0.56-0.96], p=0.024), total cardiovascular events (389 vs
486, 0.79 [0.69-0.90], p=0.0005), and total coronary events (178 vs 247,
0.71 [0.59-0.86], p=0.0005) were also significantly lowered. There were 185
deaths in the atorvastatin group and 212 in the placebo group (0.87
[0.71-1.06], p=0.16). Atorvastatin lowered total serum cholesterol by about
1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3
years of follow-up. INTERPRETATION: The reductions in major cardiovascular
events with atorvastatin are large, given the short follow-up time. These
findings may have implications for future lipid-lowering guidelines."


Note the sentence, "There were 185 deaths in the atorvastatin group and 212
in the placebo group (0.87 [0.71-1.06], p=0.16)." The study wasn't powered
to compare mortality between treatment and control groups, even for the full
study population.

They also state: "There was no significant heterogeneity among prespecified
subgroups."

The prespecified subgroups didn't include the sexes, according to the first
abstract I posted. The paper is in the Lancet, unfortunately, which never
provides free public access to the full text of papers.

Why do you regard this primary-prevention study that lacked mortality as an
endpoint and that found the difference in the observed death rate of treated
and untreated (no 10 mg of atorvastatin) significant at only p<0.16 to be of
interest here?
--
Jim Chinnis Warrenton, Virginia, USA
.

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