On aspirin Meta study What about Plavix?

http://www.theheart.org/article/975967.do

Meta-analysis questions use of aspirin in primary prevention
JUNE 3, 2009 | Sue Hughes
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Oxford UK - The authors of a new meta-analysis of aspirin use in primary
prevention say their results "do not seem to justify general guidelines
advocating the routine use of aspirin in all healthy individuals above a
moderate level of risk for coronary heart disease. [1]"
The meta-analysis, published in the May 30, 2009 issue of the Lancet,
was conducted by the Antithrombotic Trialists' (ATT) Collaboration, led
by Dr Colin Baigent (Clinical Trial Service Unit, Oxford University, UK).
Baigent commented to heartwire: "The present data that we have reported
here have not been previously available. The current guidelines are
based on previous meta-analyses, which have limitations.



We have shown for the first time that the very same people at higher
risk of heart disease are also at higher bleeding risk with aspirin,
which is a very important piece of information and should influence the
way in which aspirin is used."




He added: "Medicine has moved on in recent years, and we now know that
we can safely reduce risk of heart disease by lowering cholesterol and
blood pressure, and the drugs used to lower these risk factors are
probably safer than aspirin. A person wanting to lower their risk might
well consider taking a statin or an antihypertensive first and only
after that add in a less safe drug like aspirin."

(((( Bill hates Lipitor.)))))

Baigent pointed out that the present guidelines, recommending aspirin
for primary prevention in all people above a certain risk, are not
supported by this new meta-analysis. "It is not for us to recommend
changes in guidelines, but I would think the guidelines committees would
now want to review their recommendations in light of these new
findings," he said. "I'm not saying you should never use aspirin for
primary prevention, and certain individuals may wish to still take it
after discussing the risks and benefits with their doctor, which I think
is fine. But our data suggest there is not good evidence of substantial
benefit that outweighs risk enough to justify a public policy
recommending routine use above a moderate CHD risk in primary
prevention."
He added that this advice does not affect recommendations for secondary
prevention, where the absolute benefit of aspirin is much greater and
vastly outweighs the risk of bleeding.

Decision should be made on individual basis?

Commenting on the paper for heartwire, Dr Deepak Bhatt (Brigham and
Women's Hospital, Boston, MA) agreed with Baigent. He described the
meta-analysis as "very well-done" with "robust" findings. "The authors
identify a benefit of aspirin in primary prevention on nonfatal ischemic
events that is largely counterbalanced by an increase in bleeding
events, including a small increase in hemorrhagic stroke, with no net
effect on vascular mortality. That the risk factors for ischemic events
were similar for bleeding events is an interesting observation on its
own. The effects in men and women were more similar than dissimilar,
which makes biological sense for antiplatelet therapy," Bhatt noted.
"Therefore, I think for now, the decision of whether to use aspirin for
primary prevention should be based on a thoughtful assessment of
ischemic and bleeding risks by the physician and patient on an
individual basis. I think it is a mistake for patients to decide to
start aspirin for primary prevention without consulting their
physicians. Ongoing trials should help clarify which patients in the
large primary-prevention universe really ought to be on aspirin," he
added.

Previous meta-analyses had limitations

In the paper, the authors explain that for patients who already have
occlusive vascular disease, the benefit of long-term aspirin treatment
in reducing vascular events has been clearly shown to be much greater
than the risk of bleeding, but for primary prevention, the balance of
risk and benefit is less clear. This is because the patients are at
lower risk of vascular disease and the absolute benefits of aspirin are
therefore an order of magnitude lower than in secondary prevention.
They point out that previous meta-analyses of aspirin primary-prevention
trials were not based on individual participant data, so they could not
reliably compare the benefits and risks of aspirin in prognostically
important groups (such as older people and others at increased risk of
coronary heart disease) and could not quantify reliably the extent to
which people at increased risk of coronary heart disease might also be
at increased risk of bleeding. Therefore, current guidelines largely
ignore any differences in bleeding risk and recommend that aspirin be
used widely for primary prevention in those at moderately raised risk of
heart disease, and, as age is a major determinant of the risk of
coronary heart disease, the guidelines recommend that daily aspirin
should be started in all people above a specific age, they add.
In view of the limitations of the analyses underlying current
guidelines, the authors collated a meta-analysis of individual
participant data, established involving the principal investigators of
all large trials of primary prevention with aspirin.
Results from the six primary-prevention trials showed that serious
vascular events occurred at a rate of 0.51% per year in people allocated
to aspirin compared with 0.57% per year in controls. This absolute
reduction of 0.07% per year represented a 12% proportional reduction.
The risk of major bleeds was increased with aspirin from 0.07% to 0.10%
per year, an absolute increase of 0.03%.

Proportional reduction in vascular events similar in all subgroups

This proportional reduction in serious vascular events did not depend
significantly on age, sex, smoking history, blood pressure, total
cholesterol, body-mass index, history of diabetes, or predicted risk of
coronary heart disease. The authors point out that there was not even a
significant trend in the proportional effects of aspirin in people at
very low, low, moderate, and high estimated risk of coronary heart
disease. "If the proportional risk reductions in these different
subgroups really are similar, then the absolute risk reductions will
depend chiefly on an individual's absolute risk without treatment," the
authors comment.
They calculate that irrespective of age or sex, the absolute reduction
in occlusive events in the primary-prevention population would be only
about twice as large as the absolute increase in bleeding. And they
further point out that most people in these trials were not taking
statins, which would have reduced both MI and stroke with little hazard.
Noting that generic statins are now widely available at low cost, they
suggest that because of their efficacy and safety, primary prevention by
a statin could well be preferred to primary prevention only by aspirin.
"If so, then one of the main questions for aspirin in primary prevention
nowadays is whether it is worthwhile to add it to a statin," they write.
They add that if the risk of vascular disease is already approximately
halved by statins, then the further absolute benefit of adding aspirin
could well be only about half as large as was suggested by these
primary-prevention trials, but the main bleeding hazards could well
remain. "In that case, the benefits and hazards of adding long-term
aspirin in people without preexisting disease might be of approximately
similar magnitude," they write.

Same factors determine risk of heart disease and bleeding

They also say that their analysis suggests that the same factors that
determine risk of heart disease also determine the risk of bleeding with
aspirin, so that, even for people at moderately increased risk of
coronary heart disease, the major absolute benefits and hazards of
adding aspirin to a statin-based primary-prevention regimen could still
be approximately evenly balanced.
"Drug safety is of particular importance in public-health
recommendations for large, apparently disease-free populations; there
should be good evidence that benefits exceed risks by an appropriate
margin. Hence, although the currently available trial results could well
help inform personally appropriate judgments by individuals about their
own use of long-term aspirin, they do not seem to justify general
guidelines advocating the routine use of aspirin in all apparently
healthy individuals above a moderate level of risk of coronary heart
disease," the authors conclude.

Editorial tries to define groups that would benefit

In an accompanying editorial [2], Drs Ale Algra and Jacoba Greving
(University Medical Center, Utrecht, the Netherlands) use the data from
the current meta-analysis to update a cost-effectiveness analysis that
they performed previously. Whereas the authors of the current
meta-analysis analyzed data from men and women together to draw their
main conclusions, Algra and Greving used the slightly different risk
ratios for cardiac events and ischemic stroke for women and men
separately. They summarize their results in the following table, which
suggests that aspirin should be recommended for the higher-risk
primary-prevention populations.
Risk of vascular disease and aspirin recommendations for aspirin use in
men and women of different ages

Age, y
Women
Women
Men
Men

10-y vascular risk (%)
Aspirin recommended
10-y vascular risk (%)
Aspirin recommended
40-49




Average risk
1
No
4
No
2x average risk
3
No
7
No
5x average risk
7
No
18
No
50-59




Average risk
3
No
8
No
2x average risk
6
No
15
No
5x average risk
15
No
34
Yes
60-69




Average risk
8
No
14
No
2x average risk
15
No
26
Yes
5x average risk
34
Yes
53
Yes
70-79




Average risk
16
No
20
Yes
2x average risk
30
Yes
35
Yes
5x average risk
60
Yes
66
Yes

To download table as a slide, click on slide logo above


Baigent unimpressed with editorial

But Baigent told heartwire that he did not agree with the editorialists'
table. "I don't know exactly how they have done their calculations, but
I don't think they have considered our data in a consistent enough way.
They have used a model with some assumptions in it, and these models
generally don't perform well. I don't think it is a particularly helpful
way of interpreting the data we've published," he said.
He pointed out that unfortunately there is no easy way to define who
should take aspirin for primary prevention. "There is no easy formula,
but this is not an easy question," he commented. When asked how he would
advise primary-care doctors to make this decision, Baigent answered: "If
a patient has lots of risk factors?eg, they are overweight, smoke, and
have high cholesterol, then aspirin would be reasonable on top of statin
therapy. It may well be that the level of risk that GPs consider
justifies aspirin use just increases somewhat," he sugges

--
Garden in shade zone 5 S Jersey USA

No foreign intervention unless tyranny at home.








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