IL MEDICO E L’IPERTENSIONE Burgarella Editore International Come si misura la pressione arteriosa Qual'è il più comune metodo di misurazione della pressione arteriosa Il più comune metodo di misurazione della pressione arteriosa è quello ascoltatorio, utilizzando lo sfigmomanometro. Nel monitoraggio pressorio e nella automisurazione si utilizza sempre più il metodo oscil
Aspirin not recommendedAspirin Not Recommended
For Heart Disease Anymore
by Dr. John G. F. Cleland 1/2002
Despite the vast size of these meta-analyses, the evidence in support of
aspirin preventing atherosclerotic events
is still inconclusive. The third meta-analysis from the Antithrombotic
Trialists' Collaboration contains data on over 100,000 patients at high risk of
atherosclerotic events, representing more than 250, 000 patient years of
follow up. (1)
This meta-analysis and its predecessors form the major argument for the
current widespread fashion of prescribing aspirin to such patients. (2, 3) It is
an enormous body of research and the collaboration is to be congratulated
for having gathered so much data. However, quality as well as quantity
matters. And the quality is such that the results can only
• The series of meta-analyses on the anti-platelet activity of aspirin
overvalues aspirin's effectiveness and safety.
• All the large long term trials of aspirin after myocardial infarction show no
effect on mortality.
• Aspirin may change the way vascular events present rather than prevent
• This may lead to a "cosmetic" reduction in non-fatal events and an increase
in sudden death.
• Data on the safety and cost-benefit of aspirin are inadequate.
• Advocating the use of aspirin for preventing atherosclerotic events diverts
attention from other, more effective,
Trials Do Not Show That Aspirin Saves Lives
Meta-analysis is increasingly viewed either as a way of verifying that the
outcome of an individual trial is consistent with the rest of the known data or
as a way of generating a hypothesis. However, in the absence of a
definitively positive trial, many consider meta-analysis inadequate evidence
for clinical decision making. The series of metaanalyses from the trialists'
collaboration contains serious additional flaws.(3-6) It is remarkable and
probably statistically significant how seldom trials of anti-platelet agents
have shown benefit on their selected primary outcome. The choice of the
primary endpoint by the Antithrombotic Trialists' Collaboration is
arbitrary and suspect.
Antiplatelet agents seem to be substantially more effective in reducing the
incidence of non-fatal events than in reducing death. Indeed, among large
long-term trials after myocardial infarction there is no evidence that
aspirin saves lives.
An intervention can reduce non-fatal events in three ways: by genuinely
reducing them, by concealing them, or by converting non-fatal events into
fatal ones. The failure of aspirin to reduce mortality despite a reduction in
non-fatal events in many studies suggests that aspirin may conceal, rather
than prevent, vascular events. (6)
Epidemiological data suggest that 25% of non-fatal myocardial infarctions
are silent.(4,5) As aspirin, even at low doses, is an analgesic and because it
may provoke dyspepsia, which may create confusion about the cause of
chest pain, it is not difficult to believe that aspirin could increase the
proportion of silent events from 25% to 30%. This could
explain all the benefits of antiplatelet agents on non-fatal myocardial in the
Aspirin increased the risk of sudden death in every long-term study
after myocardial infarction that reported
such events. 38
This increase was from 4.4% on placebo to 5.6% on aspirin in the
persantine-aspirin reinfarction (PARIS) study; from 2.0% to 2.7% in the
aspirin myocardial infarction study (AMIS); and from 2.0% to 2.4% in the
persantine-aspirin reinfarction study (PARIS-II).(9)
This could reflect an increased risk of sudden death among concealed, and
therefore untreated, events. Another possible mechanism by which aspirin
may convert non-fatal events into fatal ones is by increasing the risk of
hemorrhagic conversion of cerebral and myocardial infarctions.
All cause mortality and, arguably, disabling stroke are the only robust
markers of benefit with an antiplatelet agent. It is not clear that antiplatelet
agents reduce the risk of either.
Some trials that were included lost more than a quarter of their patients to
follow up(10) In similar circumstances, with other agents, it has been
suggested that all patients lost to follow up in the active treatment group
should be considered to have died and none of those in the control arm. Such
an analysis would neutralize the benefit observed in one of the few
seemingly convincingly positive studies of aspirin, the ISIS-2 trial.(11)
Bias In Interpretation
The Antithrombotic Trialists' Collaboration shows bias in the analysis and
interpretation of their results. We are given
scant detail on how the numbers of events credited to each trial changed
between meta-analyses. (2, 3) Trials were retrospectively reanalyzed,
resulting in resurrection of a number of apparently dead patients and the
discovery of a number of new deaths.
Most interventions probably help some people some of the time and harm
others some of the time. A small benefit could reflect a small overall benefit
in a large population or a substantial benefit in some patients and harm in
Aspirin could exert a short-term benefit followed by long term harm, in
which case the benefits and safety of aspirin could be increased by using
only a short term course of therapy. (14) Aspirin may be harmful in patients
with coronary disease and heart failure.(5, 6, 12)
The evidence for an adverse interaction between aspirin and angiotensin
converting enzyme inhibitors observed in the SOLVD (studies of left
ventricular function) and HOPE (heart outcomes prevention evaluation)
trials is also a matter for concern.(6, 12) These are important issues that have
not been adequately addressed.
Neither Safe Nor Cheap
Many believe that, even if aspirin is not effective, it is safe. Aspirin does
appear to be relatively safe for the patients included in clinical trials, but as
these studies excluded by design patients at risk of adverse events with
aspirin and tended to include younger patients with lower multiple morbidity
it is likely that aspirin is not as safe as suggested.
Low dose aspirin for cardiovascular prophylaxis may account for more
than 30% of all major gastrointestinal hemorrhage in patients (4, 6, 15)
and may also be associated with an increased risk of renal failure.
Finally, there is a widespread view that aspirin is cheap. However, when
evaluating the costs of treatment the amount and type of benefit and the
costs of managing adverse effects also need to be evaluated. Very few
economic appraisals of aspirin have been done.
One such analysis, recently commissioned by the chief scientist's office in
Scotland, suggested it may cost more than £80 000 to prevent one event with
aspirin for primary prevention and more than £3000 for secondary
prevention. (16) These analyses have assumed that aspirin is as effective as
the meta-analyses suggest, which may not be true.
A Diversion: Perhaps the greatest potential detriment of aspirin on health
care, however, is that it diverts attention away from treatments that are of
unequivocal benefit to many groups of patients. The reader should not
accept theconclusions of the Antithrombotic Trialists' Collaboration
uncritically but rather read the original papers on whichtheir conclusions are
1. Antithrombotic Trialists' Collaboration. Prevention of death, myocardial
infarction and stroke by antiplatelet therapy in high-risk patients. BMJ 2001;
2. The antiplatelet trialists' collaboration. Secondary prevention of vascular
disease by prolonged antiplatelet treatment. BMJ 1988; 296: 320-
3. The antiplatelet trialists' collaboration. Collaborative overview of
randomized trials of antiplatelet therapy - 1:Prevention of death, myocardial
stroke by prolonged antiplatelet therapy in various categories of patients.
BMJ 1994; 308: 81-106[Abstract/Full Text].
4. Cleland JGF, Bulpitt CJ, Falk RH, Findlay IN, Oakley CM, Murray G, et
al. Is aspirin safe for patients with heart failure? Br Heart J 1995; 74: 215-
5. Cleland JGF. Anticoagulant and antiplatelet therapy in heart failure. Curr
Opinion Cardiol 1997; 12: 276-287[Medline].
6. Cleland JGF, John J, Houghton T. Does aspirin attenuate the effect of
angiotensin-converting enzyme inhibitors in hypertension or heart failure?
Nephrol Hypertens 2001; 10: 625-631[Medline].
7. The Persantine-Aspirin Reinfarction Study (PARIS) Research Group.
Persantine and aspirin in coronary heart disease. Circulation 1980; 62: 449-
8. The Aspirin Myocardial Infarction Study Research Group. The aspirin
myocardial infarction study: final results. Circulation 1980; 62: V79-
9. Klimit CR, Knatterud GL, Stamler J, Meier P. Persantine-aspirin
reinfarction study. Part II. Secondary coronary prevention with persantine
and aspirin. J Am
Coll Cardiol 1986; 7: 251-269[Medline].
10. Breddin K, Loew D, Uberla KK, Walter E. The German-Austrian aspirin
trial: A comparison of acetylsalicylic acid, placebo and phenprocoumon in
secondary prevention of myocardial infarction. Circulation 1980; 62: V63-
11. ISIS-2 Collaborative group. Randomised trial of intravenous
streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected
infarction. Lancet 1988; ii: 349-360.
12. Jones CG, Cleland JGF. Meeting report - LIDO, HOPE, MOXCON and
WASH Studies. Eur J Heart Failure 1999;425-31.
13. Pulmonary Embolism Prevention (PEP) Trial Collaborative Group.
Prevention of pulmonary embolism and deep vein thrombosis with low dose
Pulmonary Embolism Prevention (PEP) trial. Lancet 2000; 355: 1295-
14. Lewis HD, Davis JW, Archibald DG, Steinke WE, Smitherman TC,
Doherty JE, et al. Protective effects of aspirin against acute mycardial
death in men with unstable angina. N Engl J Med 1983; 309: 396-
15. Weil J, Langman MJS, Wainwright P, Lawson DH, Rawlins M, Logan
RFA, et al. Peptic ulcer bleeding: accessory risk factors and interactions with
anti-inflammatory drugs. Gut 2000; 46: 27-31[Abstract/Full Text].
16. McMahon AD, MacDonald TM, Davey PG, Cleland JGF. The impact of
low-dose aspirin prescribing on upper gastrointestinal toxicity, renal toxicity
healthcare resource utilization. In: Edinburgh: Chief Scientist Office,
Aspirin & Tylenol:
Linked to Kidney Failure
Reference: New England Journal of Medicine, December 20,
Individuals who have kidney disease or other ailments who regularly take
aspirin or acetaminophen may be boosting
their risk of developing kidney failure.
Researchers report that such patients who were regular users -- those who
took these painkillers at least twice a week
for 2 months -- were two to three times more likely to have the
beginning stages of chronic kidney failure,
compared with individuals who did not use these painkillers on a regular
This study and others have found that the risk is minimal in those without
pre-existing kidney disease.
Individuals who used either drug regularly were 2.5 times more likely to be
diagnosed with chronic renal failure,
compared with individuals who did not use these painkillers. The risk rose in
tandem with the amount of either drug
taken over a lifetime, the investigators found.
In looking at only participants with diabetes -- a major underlying cause of
kidney failure -- regular aspirin and
acetaminophen use were still linked to an increased risk.
The results support those of other studies that have found an association
between regular use of painkillers and an
increased risk of chronic kidney failure in susceptible individuals.
The results are consistent with exacerbating effects of acetaminophen and
aspirin on chronic renal failure, practically
regardless of accompanying disease.
About 15% of the people on dialysis today are there as a result of the
damage that Tylenol and/or aspirin did to
their kidneys. In addition, about 20% of those with heart failure are also
the result of taking NSAIDs (nonsteroidal
anti-inflammatory drugs), such as aspirin, Tylenol, etc. These drugs may
also be associated with diverticular disease
of the colon.
Pain is actually a wonderful gift – it tells us that something is wrong. Pain
is a clear signal given to us to provide
immediate feedback from our body so we can take appropriate action to
correct the problem. To mask the pain with
drugs makes about as much sense as turning off a fire alarm – so you won’t
hear it -- when your house is burning
down. The alarm is warning you that if you don’t take action, damage is
Worldwide research now tells us that many diseases that we once thought
were from genetics or poor lifestyle causes
(eating junk food, etc.) are really caused from infection. If you have any
type of pain, it may be important to begin
the use of both immune system builders, such as whole, pesticide-free
colostrum as well as natural anti-infective
agents, such as olive leaf extract, hyssop, virgin coconut oil, wild yew
extract and many others.
Prof. Dr. V. Mall Publikationsliste in print 1. Jung NH, Delvendahl I, Pechmann A, Gleich B, Gattinger N, Siebner HR, Mall V . Transcranial magnetic stimulation with a half-sine wave pulse elicits direction-specific effects in human motor cortex. BMC Neuroscience 2. Jung NH, Janzarik WG, Delvendahl I, Münchau A, Biscaldi M, Mainberger F, Bäumer T, Rauh R, Mall V . Impaired in