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2013 ; 17
(43
): 1-253
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English Wikipedia
Aspirin for prophylactic use in the primary prevention of cardiovascular disease
and cancer: a systematic review and overview of reviews
#MMPMID24074752
Sutcliffe P
; Connock M
; Gurung T
; Freeman K
; Johnson S
; Kandala NB
; Grove A
; Gurung B
; Morrow S
; Clarke A
Health Technol Assess
2013[Sep]; 17
(43
): 1-253
PMID24074752
show ga
BACKGROUND: Prophylactic aspirin has been considered to be beneficial in reducing
the risks of heart disease and cancer. However, potential benefits must be
balanced against the possible harm from side effects, such as bleeding and
gastrointestinal (GI) symptoms. It is particularly important to know the risk of
side effects when aspirin is used as primary prevention--that is when used by
people as yet free of, but at risk of developing, cardiovascular disease (CVD) or
cancer. In this report we aim to identify and re-analyse randomised controlled
trials (RCTs), systematic reviews and meta-analyses to summarise the current
scientific evidence with a focus on possible harms of prophylactic aspirin in
primary prevention of CVD and cancer. OBJECTIVES: To identify RCTs, systematic
reviews and meta-analyses of RCTs of the prophylactic use of aspirin in primary
prevention of CVD or cancer. To undertake a quality assessment of identified
systematic reviews and meta-analyses using meta-analysis to investigate
study-level effects on estimates of benefits and risks of adverse events;
cumulative meta-analysis; exploratory multivariable meta-regression; and to
quantify relative and absolute risks and benefits. METHODS: We identified RCTs,
meta-analyses and systematic reviews, and searched electronic bibliographic
databases (from 2008 September 2012) including MEDLINE, Cochrane Central Register
of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Centre for
Reviews and Dissemination, and Science Citation Index. We limited searches to
publications since 2008, based on timing of the most recent comprehensive
systematic reviews. RESULTS: In total, 2572 potentially relevant papers were
identified and 27 met the inclusion criteria. Benefits of aspirin ranged from 6%
reduction in relative risk (RR) for all-cause mortality [RR 0.94, 95% confidence
interval (CI) 0.88 to 1.00] and 10% reduction in major cardiovascular events
(MCEs) (RR 0.90, 95% CI 0.85 to 0.96) to a reduction in total coronary heart
disease (CHD) of 15% (RR 0.85, 95% CI 0.69 to 1.06). Reported pooled odds ratios
(ORs) for total cancer mortality ranged between 0.76 (95% CI 0.66 to 0.88) and
0.93 (95% CI 0.84 to 1.03). Inclusion of the Women's Health Study changed the
estimated OR to 0.82 (95% CI 0.69 to 0.97). Aspirin reduced reported colorectal
cancer (CRC) incidence (OR 0.66, 95% CI 0.90 to 1.02). However, including studies
in which aspirin was given every other day raised the OR to 0.91 (95% CI 0.74 to
1.11). Reported cancer benefits appeared approximately 5 years from start of
treatment. Calculation of absolute effects per 100,000 patient-years of follow-up
showed reductions ranging from 33 to 46 deaths (all-cause mortality), 60-84 MCEs
and 47-64 incidents of CHD and a possible avoidance of 34 deaths from CRC.
Reported increased RRs of adverse events from aspirin use were 37% for GI
bleeding (RR 1.37, 95% CI 1.15 to 1.62), between 54% (RR 1.54, 95% CI 1.30 to
1.82) and 62% (RR 1.62, 95% CI 1.31 to 2.00) for major bleeds, and between 32%
(RR 1.32, 95% CI 1.00 to 1.74) and 38% (RR 1.38, 95% CI 1.01 to 1.82) for
haemorrhagic stroke. Pooled estimates of increased RR for bleeding remained
stable across trials conducted over several decades. Estimates of absolute rates
of harm from aspirin use, per 100,000 patient-years of follow-up, were 99-178 for
non-trivial bleeds, 46-49 for major bleeds, 68-117 for GI bleeds and 8-10 for
haemorrhagic stroke. Meta-analyses aimed at judging risk of bleed according to
sex and in individuals with diabetes were insufficiently powered for firm
conclusions to be drawn. LIMITATIONS: Searches were date limited to 2008 because
of the intense interest that this subject has generated and the cataloguing of
all primary research in so many previous systematic reviews. A further limitation
was our potential over-reliance on study-level systematic reviews in which the
person-years of follow-up were not accurately ascertainable. However, estimates
of number of events averted or incurred through aspirin use calculated from data
in study-level meta-analyses did not differ substantially from estimates based on
individual patient data-level meta-analyses, for which person-years of follow-up
were more accurate (although based on less-than-complete assemblies of currently
available primary studies). CONCLUSIONS: We have found that there is a fine
balance between benefits and risks from regular aspirin use in primary prevention
of CVD. Effects on cancer prevention have a long lead time and are at present
reliant on post hoc analyses. All absolute effects are relatively small compared
with the burden of these diseases. Several potentially relevant ongoing trials
will be completed between 2013 and 2019, which may clarify the extent of benefit
of aspirin in reducing cancer incidence and mortality. Future research
considerations include expanding the use of IPD meta-analysis of RCTs by pooling
data from available studies and investigating the impact of different dose
regimens on cardiovascular and cancer outcomes. FUNDING: The National Institute
for Health Research Health Technology Assessment programme.
|Adult
[MESH]
|Aged
[MESH]
|Aspirin/*adverse effects/*therapeutic use
[MESH]
|Cardiovascular Diseases/mortality/*prevention & control
[MESH]
|Colorectal Neoplasms/mortality/prevention & control
[MESH]
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