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III Congresso Nazionale
17/19 Maggio 2013
Atlantic Hotel - Riccione
Aspirina e Prevenzione primaria
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Claudio Ferri
Università dell’Aquila
Cattedra e Scuola di Medicina Interna – Dipartimento MeSVA
Divisione di Medicina Interna Universitaria – Ospedale San Salvatore
Antithrombotic therapy and prevention of CV disease
SCA
Sec.Pr.
MI
Sec.Pr.
STROKE
Eur Heart J 2012, 33:1636-1701
Absolute risk difference in relation to
placebo in primary prevention trials
Absolute number of nontrivial bleedings
caused versus nonfatal MIs averted
Absolute number of nontrivial bleedings caused versus total CV events averted
Seshasai SR et al, Arch Intern Med. 2012;172(3):209-216
Aspirina e Prevenzione cardiovascolare secondaria
Summary of Recommendations
3.1.1-3.1.5. For patients with established coronary artery disease
(CAD), defined as patients 1-year post-acute coronary syndrome
(ACS), with prior revascularization, coronary stenoses > 50% by
coronary angiogram, and/or evidence for cardiac ischemia on
diagnostic testing, (including patients after the first year post-ACS
and/or with prior coronary artery bypass graft [CABG] surgery):
We recommend long-term single antiplatelet therapy with
aspirin 75 to 100 mg daily or clopidogrel 75 mg daily over
no antiplatelet therapy (Grade 1A).
We suggest single over dual antiplatelet therapy with aspirin
plus clopidogrel (Grade 2B).
Copyright: American College of Chest Physicians 2012© - Chest. 2012; 141(2 Suppl): e637S–e668S.
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Aspirina e Prevenzione cardiovascolare primaria
Summary of Recommendations
2.1.For persons aged 50 years or older without symptomatic
cardiovascular disease, we suggest low-dose aspirin 75 to 100
mg daily over no aspirin therapy (Grade 2B).
Remarks: Aspirin slightly reduces total mortality regardless of cardiovascular
risk profile if taken over 10 years. In people at moderate to high risk of
cardiovascular events, the reduction in myocardial infarction (MI) is closely
balanced with an increase in major bleeds. Whatever their risk status, people who
are averse to taking medication over a prolonged time period for very small
benefits will be disinclined to use aspirin for primary prophylaxis. Individuals
who value preventing an MI substantially higher than avoiding a GI bleed will
be, if they are in the moderate or high cardiovascular risk group, more likely to
choose aspirin.
Copyright: American College of Chest Physicians 2012© - Chest. 2012; 141(2 Suppl): e637S–e668S.
Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Effectiveness of quality improvement strategies on the management of diabetes:
a systematic review and meta-analysis – 48 cluster trials 84.865 patients
Variables
HbA1c
Changes vs usual care
LDL cholesterol
Statin use
0·10 mmol/L (0·05—0.14; 47 trials)
(RR 1·12, 0·99—1·28, 10 trials)
SBP
3·13 mm Hg (2·19—4·06, 65 trials)
DBP
Hypertension control
1·55 mm Hg (0·95—2·15, 61 trials)
(RR 1·01, 0·96—1·07, 18 trials)
Smoking cessation
(RR 1·13, 0·99—1·29, 13 trials)
0·37% (95% CI 0·28—0·45; 120 trials)
Likelihood to receive:
Aspirin
(RR 1·33, 1·21—1·45,11 trials)
Antihypertensive drugs
Screening for: Retinopathy
Renal function
Foot abnormalities
(RR 1·17, 1·01—1·37, 10 trials)
(RR 1·22, 1·13—1·32, 23 trials)
(RR 1.28, 1·13—1·44, 14 trials)
(RR 1·27, 1·16—1·39, 22 trials)
Tricco AC et al Lancet. 2012;379(9833):2252-61.
The Melbourne Colorectal Cancer Study
Distribution of medication among cases and controls and relative risk estimates
*
* 0,63 (0.50-0.78) p<0.001 after adjustment for arthritis
Authors wrote about ASA-related decrements in cancer: “consistent for both
colon and rectal cancer and for both males and females”
Kune GA, Kune S, Watson LF. Cancer Res. 1988;48(15):4399-404.
Incidence of cancer
Effect of allocation to aspirin versus placebo (A)
and warfarin versus placebo (B) on the incidence
of cancer during the Thrombosis Prevention Trial
Rothwell PM et al Lancet 2012, 379, 9826: 1602–1612
Aspirin Is Associated With Lower Melanoma Risk Among
Postmenopausal Caucasian Women
ASA users: p linear trend = 0.01
NSAID users: p linear trend = 0.8
1.2
1
1.0
Hazard Ratio
0.8
ASA users
NSAID users
(NON-ASA)
0.6
0.4
0.2
0
A
S
A
A
S
A
u
s
e
r
s
u
s
e
r
s
<1 year
1-4 years
A
S
A
NONE (ref)
u
s
e
r
s
≥5
Incidence per 100.000 person per year HR (fully adjusted, vs NSAID nonusers)
ASA users
69.8
0.79 (0.63-0.98)
NSAID users (NON-ASA)
87.9
1.05 (0.83-1.34)
Gamba CA et al Cancer 2013
Incidence of cancer
Effect of aspirin on incidence of cancer during six randomised trials of daily low-dose (75–100mg daily)
aspirin versus placebo in primary prevention of vascular events (A) All patients. (B) All patients with
scheduled duration of trial treatment of at least 5 years. (C) Meta-analysis of the effect of aspirin on risk of
non-vascular death during 12 randomised trials in primary prevention
C
Figure 2 Pooled analysis of effect of allocation to aspirin on incidence of cancer during six randomised trials
of daily low-dose (75?100mg daily) aspirin versus placebo in primary prevention of vascular events<ce:crossrefs refid="bib16 bib17 bi...
Rothwell PM et al Lancet 2012, 379, 9826: 1602–1612
Meta-analyses of the effect of aspirin on risks of incident cancer, major
vascular events, and major extracranial bleeds during six randomised
trials of daily low-dose aspirin versus control in primary prevention of
vascular events stratified by period of trial follow-up
Rothwell PM et al Lancet 2012, 379, 9826: 1602–1612
RR of colorectal cancer for highest vs lowest categories of ASA use
Dose of ASA use and risk of colorectal cancer
Years of ASA use and risk of colorectal cancer
Frequency of ASA use and risk of colorectal cancer
18% decreased risk for 10
years aspirin increment
Ye X et al Plos One 2013; 8(2): e57578.
Global Health Benefits from ASA: Pooled analyses of the six randomised trials of
daily low-dose (75–100 mg daily) aspirin versus placebo in primary prevention
(A) composite outcome of major vascular events, cancer, or fatal extracranial haemorrhage
(B) major vascular events, cancer, or any extracranial haemorrhage
Rothwell PM et al Lancet 2012, 379, 9826: 1602–1612
Aspirin use and risk of cancer
Algra AM and Rothwell PM Lancet Oncol. 2012;13(5):518-27.
Aspirin use and risk of cancer metastasis
Algra AM and Rothwell PM Lancet Oncol. 2012;13(5):518-27.
Gobal benefits from ASA: Reduction in CV events and cancer incidence
1) The time-dependent ability of ASA to reduce
cancer incidence (not only colo-rectal and even
metastatic) is evident
2) This cancer reduction modulates benefits
and risk in favour of ASA use even in primary
prevention
3) We need appropriate trials (?)
4) We need to understand
Evidence That Acetylsalicylic Acid Attenuates Inflammation in
the Walls of Human Cerebral Aneurysms
Hasan DM et al J. Am. Heart Assoc. 2013, 2
The role of aspirin in cancer prevention
Females, age 50–59 years
Females, age 65–74 years
Males, age 50–59 years
Males, age 65–74 years
Michael J. Thun, Eric J. Jacobs and Carlo Patrono Nat. Rev. Clin. Oncol. 2012, 9, 259–267
Mortality among Patients with Colorectal Cancer, According to Regular
Use or Nonuse of Aspirin after Diagnosis and PIK3CA Mutation Status.
HR = 0.18
HR = 0.93
Liao X et al. N Engl J Med 2012;367:1596-1606.
Gobal benefits from ASA: Reduction in CV events and cancer incidence
1) The time-dependent ability of ASA to reduce
cancer incidence (not only colo-rectal and even
metastatic) is evident
2) This cancer reduction modulates benefits
and risk in favour of ASA use even in primary
prevention
3) We need appropriate trials (?)
4) We need to understand
5) Future surprises from ASA ?
Change in MMSE by ASA in women followed from 2000 to 2005
1–
No ASA (n.338)
ASA (n.66)
0–
-1 –
-2 –
P=0.04
-3 –
Kern S et al BMJ, 2012 Oct 3;2(5)
Serum TXB2 recovery slopes according to tertile
serum TXB2 recovery slope (ng/ml hr-1)
1
0.1
0.01
0.001
0
Serum TXB2 (ng/ml)
4
10
20
30
4
slope 0.02 [0.01-0.03] ng/ml hr-1
3
2
HS
1
0
12
14
16
18
20
22
post-aspirin interval
24 hr
40
50
60
70
80
4
slope 0.07 [0.054-0.079] ng/ml hr-1
3
3
2
2
1
1
90
100 pts with type 2 DM
slope 0.14 [0.11-0.20] ng/ml hr-1
0
0
12
14
16
18
20
22
post-aspirin interval
24 hr
12
14
16
18
20
22
post-aspirin interval
24 hr
Rocca B. et al. J Thromb Haemost 2012;10:1220-30
Serum TXB2 recovery slopes in diabetic patients in the upper tertile,
before and after the randomized phase of the study
Rocca B. et al. J Thromb Haemost 2012;10:1220-30