North of Tyne anti-platelet guidelines: use in primary care
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Transcript of North of Tyne anti-platelet guidelines: use in primary care
North of Tyne anti-platelet guidelines: use in primary care
Jane S SkinnerConsultant 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
0
5
10
15
20
25
Previous MI Acute MI Previous stroke/TIA
Acute stroke
Other high risk
13.5%
17.0%
10.4%
14.2%17.8%
21.4%
8.2%9.1%
8.1%
10.2%
Adj
uste
d %
vas
cula
r eve
nts
ATC BMJ 2002;324:71
Anti-plateletPlacebo
Mean months of treatment 27 1 29 0.7 22
Aspirin reduced the risk of serious vascular events (non-fatal MI, non fatal
stroke or vascular death) by about a quarter (ATC BMJ 2002;324:71)
In a more recent meta-analysis aspirin reduced the risk of serious vascular
events by 19% (Lancet 2009;373:1849-60)
19,185 patients recent acute MI, recent acute ischaemic stroke or
symptomatic PADAspirin 325 mg od versus clopidogrel 75 mg od
CAPRIE Lancet 1996;348:1329-39
Annual risk of a major vascular event 5.32% with clopidogrel vs 5.83% with aspirinNo major differences in terms of safety
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
0
2
4
6
8
10
Recurrent ulcer bleeding Lower GI bleeding
Probability of recurrent bleeding at 12 months
(%)
Aspirin 80mg od plus esomeprazole 20mg bd (n=159)Clopidogrel 75mg od plus placebo (n=161)
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
Cyclo-oxygense
Plaque ruptureOther sources
Eg damaged endothelium
ADP RELEASE ADP RELEASE ADP RELEASE
PLATELET ADP RECEPTOR
PLATELET AGGREGATION
ASPIRIN
THIENOPYRIDINE
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
NEJM 2001;345:494
Aspirin vs aspirin plus clopidogrel in ACS without ST elevation
Clopidogrel + ASA
3 6 9
Placebo + ASA
Months of Follow-Up
11.4%
9.3%
20% RRRP < 0.001
N = 12,562
0 120.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
Cum
ulat
ive
Haz
ard
Rat
e Δ2.1%
Excess of 1 life-threatening and 6 major bleeds per 1000 patients treated with clopidogrel
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
0
5
10
15
0 90 180 270 360 450
HR 0.81(0.73-0.90)P=0.0004
Prasugrel
Clopidogrel
Days
Endp
oint
(%)
12.1
9.9
HR 1.32(1.03-1.68)P=0.03
Prasugrel
Clopidogrel1.82.4
1o EP: CV Death / MI / Stroke
TIMI Major NonCABG Bleeds
TITAN
Wiviott et al., NEJM 2007; 357: 2001-5
TRITON-TIMI 38
Aspirin vs aspirin and clopidogrel in stable patients
CHARISMA New Engl J Med 2006;354
p=0.22
Primary Efficacy Outcome = MI, Stroke, or CV Death)
Median follow up 28 mths
Moderate bleeding2.1% clopidogrel vs 1.3% placebo
Initiation of combination treatment with aspirin and clopidogrel is not
recommended in stable patients with vascular disease
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
CV
dea
th, M
I or s
troke
Days
CLOPIDOGREL PPI vs no PPI: Adj HR 0.94, 95% CI 0.80-1.11
PPI use at randomization (n= 4529)
Clopidogrel
Prasugrel
PRASUGREL PPI vs no PPI: Adj HR 1.00, 95% CI 0.84-1.20
Primary endpoint stratified by use of PPI
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