Transcript Men and women admitted with acute myocardial infarction

North of Tyne anti-platelet
guidelines: use in primary care
Jane S Skinner
Consultant Community Cardiologist
Purpose of the presentation
• To summarise key points for treatment with
anti-platelet agents in primary care North of
Tyne
• To include some key evidence to support
the recommendations
Which anti-platelet agents are
prescribed in primary care?
• Aspirin
• Thienopyridines
– Clopidogrel
– Prasugrel
• Dipyridamole
Indications for anti-platelet
agents in primary care
• Secondary prevention in atheromatous
vascular disease
– Coronary disease
– Cerebrovascular disease
– Peripheral arterial disease
• Atrial fibrillation
• Primary prevention
Secondary prevention
• Aspirin 75 mg daily
– First line, long term treatment
– Not enteric coated
– In some patients a higher dose may be
recommended from specialist care eg after
CABG
• Clopiodgrel 75 mg od
– Only if aspirin is contra-indicated eg allergy
• Combination anti-platelet agents
Absolute effects of anti-platelet
therapy on vascular events
Adjusted % vascular events
Mean months
of treatment
27
1
29
0.7
22
Aspirin reduced the risk of serious
vascular events
Placebo (non-fatal MI, non fatal
20
Anti-platelet
stroke or
vascular death) by about a
15
quarter (ATC BMJ 2002;324:71)
21.4%
recent meta-analysis
aspirin
10In a more
17.0%
14.2%
reduced the risk
of serious vascular
10.2%
17.8%
9.1%
10.4%
5 13.5%
events by 19% (Lancet 2009;373:1849-60)
8.2%
8.1%
25
0
Previous MI Acute MI
ATC BMJ 2002;324:71
Previous Acute
stroke/TIA stroke
Other high
risk
19,185 patients recent acute MI,
recent acute ischaemic stroke or
symptomatic PAD
Aspirin 325 mg od versus clopidogrel 75 mg od
Annual risk of a major vascular event 5.32%
with clopidogrel vs 5.83% with aspirin
No major differences in terms of safety
CAPRIE Lancet 1996;348:1329-39
Dyspepsia with aspirin
• Review and modify other contributory factors
– Excess alcohol
– NSAIDs, steroids
•
•
•
•
•
Investigate if appropriate
Take aspirin with food
Reduce aspirin dose to 75 mg od
Use aspirin in combination with a PPI
Do not switch to enteric coated
Recurrent GI bleeding; aspirin
plus PPI vs clopidogrel
10
Probability
of recurrent
bleeding at
12 months
(%)
Aspirin 80mg od plus
esomeprazole 20mg bd (n=159)
Clopidogrel 75mg od
plus placebo (n=161)
8
6
4
2
0
Recurrent ulcer bleeding
Lower GI bleeding
NEJM 2005;352:238-44
Key messages in long term
secondary prevention
• Aspirin first line
– Individual high risk patients, clopidogrel on consultant
recommendation
• Allergic to aspirin
– Consider clopidogrel
• Dyspepsia with aspirin
– Routine measures
– Consider the addition of a PPI
• History of upper GI bleeding or ulcer with aspirin
– Heal ulcer, HP erradication
– Addition of PPI to aspirin
Combination anti-platelet agents
• Aspirin plus thienopyridine
– Clopidogrel
– Prasugrel
• Aspirin plus dipyridamole
PLATELET ACTIVATION
ASPIRIN
Cyclo-oxygense
Other sources
Eg damaged endothelium
Plaque rupture
ADP RELEASE
ADP RELEASE
PLATELET ADP RECEPTOR
THIENOPYRIDINE
PLATELET AGGREGATION
ADP RELEASE
Groups to consider
• Coronary artery disease
• Cerebrovascular disease
• After a recent acute vascular event
• After intervention
Patients with acute MI
• Thienopyridine plus aspirin
– ST elevation MI and unstable angina / non ST
elevation MI
– With or without percutaneous coronary
intervention (PCI)
– Irrespective of type of stent
• Bare metal or drug eluting
• Routinely for 12 months
Aspirin vs aspirin plus clopidogrel
in ACS without ST elevation
Cumulative Hazard Rate
0.14
11.4%
Δ2.1%
Placebo
+ ASA
0.12
9.3%
0.10
0.08
Clopidogrel
+ ASA
0.06
0.04
20% RRR
P < 0.001
N = 12,562
0.02
0.00
0
3
6
9
12
Months of Follow-Up
Excess of 1 life-threatening and 6 major bleeds
per 1000 patients treated with clopidogrel
NEJM 2001;345:494
Stable patients having elective PCI
• Aspirin 75 mg od plus
• Bare metal stent
– Clopidogrel 75 mg od for 1 month (up to 12 months
on cardiologist advice)
• Drug eluting stent
– Clopidogrel 75 mg od for 12 months then review
• Left main stem stent
– Clopidogrel 75 mg od lifelong unless advised by a
cardiologist
Clopidogrel or prasugrel in
combination with aspirin?
• Clopidogrel in many
• Prasugrel
– May be substituted for clopidogrel in some, always
started in hospital
• Prasugrel only in selected patients having PCI
–
–
–
–
Primary PCI for STEMI
Stent thrombosis occurred whilst treated with clopidgrel
Diabetes
Not if higher risk of bleeding, or after previous stroke
TITAN
TRITON-TIMI 38
15
Clopidogrel
1o EP: CV Death / MI / Stroke
Endpoint (%)
10
12.1 HR 0.81
(0.73-0.90)
P=0.0004
9.9
Prasugrel
5
TIMI Major
NonCABG Bleeds
Prasugrel
Clopidogrel
0
0
90
180
Days
270
360
2.4 HR 1.32
1.8 (1.03-1.68)
P=0.03
450
Wiviott et al., NEJM 2007; 357: 2001-5
Aspirin vs aspirin and clopidogrel in
stable patients
Primary Efficacy
Outcome = MI,
p=0.22
Initiation of combination treatment
Stroke, or CV
with aspirin and clopidogrelDeath)
is not
recommended in stable patients
with vascular diseaseMedian follow up
28 mths
Moderate bleeding
2.1% clopidogrel vs
1.3% placebo
CHARISMA New Engl J Med 2006;354
MHRA Drug Safety Update July 2009
MHRA Drug Safety Update April 2010
MHRA Drug safety update April 2010
O’Donoghie et al. Lancet 2009;374:989-997
Primary endpoint stratified by use of PPI
PPI use at randomization (n= 4529)
14%
No PPI
12%
Clopidogrel
PPI
PPI
10%
Prasugrel
CV death, MI or stroke
No PPI
8%
6%
4%
CLOPIDOGREL
PPI vs no PPI: Adj HR 0.94, 95% CI 0.80-1.11
PRASUGREL
PPI vs no PPI: Adj HR 1.00, 95% CI 0.84-1.20
2%
0%
0
100
200
Days
300
400
O’Donoghie et al. Lancet 2009;374:989-997
Key messages for combination of
aspirin and thienopyridine in CAD
• Initiated in hospital
– After MI / unstable angina
– After PCI
• Duration depends on:
– Whether MI / unstable angina
– Type of stent if elective PCI
• Not continued long term (beyond 12 months) with
some exceptions
– Advised by cardiologist
• Do not stop early without discussing with a
cardiologist
Patients after acute ischaemic stroke
• Aspirin 75 mg od and dipyridamole MR 200 mg bd
after acute ischaemic stroke
• Dipyridamole
– For at least 2 years, but may be continued indefinitely
– Relatively poorly tolerated: GI S/E, dizziness, myalgia,
headache, hypotension, hot flushes and tachycardia
– Might be limited to higher risk patients on specialist advice
– No benefit in reducing coronary events
• If aspirin allergy / not tolerated
– Clopiodgrel monotherapy not dipyridamole monotherapy
ESPRIT
• Patients
– 1363 aspirin plus dipyridamole 200mg bd (extended
release in 83%)
– 1376 aspirin alone
• Mean dose aspirin 75 mg od (range 30 to 325)
• Mean follow up 3.5 years
• Primary outcome
– Vascular death, non fatal MI, non fatal stroke, major
bleeding complication
ESPRIT Lancet 2006;367:1665-73
ESPRIT main results
ESPRIT Lancet 2006;367:1665-73
MATCH
• 7599 patients
• Ischaemic stroke or TIA within last 3 months
plus 1+ previous ischaemic stroke, MI, angina,
diabetes, symptomatic PAD in last 3 years
• Aspirin plus placebo vs aspirin plus clopidogrel
• Primary outcome: ischaemic stroke, MI,
vascular death, or rehospitalistation for acute
ischaemic event
MATCH Lancet 2004;364:331-337
MATCH Lancet 2004;364:331-337
Carotid stenting
• Planned in secondary care
• Aspirin 75 mg od plus clopidogrel 75 mg od
for 4 weeks after the procedure
– Aspirin long term
• Usually Aspirin 75 mg od plus clopidogrel
75 mg od for 7 days before the procedure
Key messages for anti-platelet
agents in patients with acute
ischaemic stroke / TIA
• National Clinical Guidelines for stroke
• Aspirin and dipyridamole standard
secondary prevention treatment following
ischaemic stroke
• For patients unable to tolerate dipyridamole
– Aspirin alone
• For patients unable to tolerate aspirin
– Clopidogrel alone
Primary prevention
• Not licensed
• Recent meta-analysis (ATT collaboration.
Lancet 2009;373:1849-60)
– 12% proportional reduction in serious vascular
events with aspirin compared to placebo, due mainly
to a reduction in non fatal MI by 23%
– Absolute reduction: 0.51% vs 0.57% per year
– Increased risk of GI and major extracranial bleeds
0.1% vs 0.07% per year
ATT collaboration. Lancet
2009;373:1849-60
ATT collaboration. Lancet 2009;373:1849-60
Key messages for aspirin in
primary prevention
• Less frequently recommended now
• Might consider in those at very high risk, but
only after considering the risks and benefits
• Only consider if blood pressure is controlled <
150/90
• High risk patients intolerant of other
preventative treatment such as statins may
have more to gain
Anti-platelet agents and surgery
• Minor surgery
– Low bleeding risk, bleeding can be easily managed
– Anti-platelet agents do not need to be withdrawn
• Endoscopy patients
• Major surgery
– Assess risks and benefits
– Clopidogrel is more likely to cause significant
bleeding problems
– Seek specialist advice, especially with combination
agents and with prior stents
Other issues
• Anti-platelet agents and anticoagulants
• Anti-platelet agents with NSAIDs
• Thromboembolic prophylaxis in patients
with AF
– Warfarin vs aspirin
– Dependent on thrombo-embolic risk
– Taking into account the risk of bleeding
Thrombo-embolic prophylaxis in AF:
Anti-platelet agents vs anticoagulation
• Use ‘scoring’ system to assess risk of
thrombo-embolism
• Take into account bleeding risk and patient
preferences when agreeing treatment
Summary
• Anti-platelet agents for prevention in
patients with or at risk of vascular disease
– Indications
– Risks
• Single agents
• Combination agents