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North of Tyne anti-platelet guidelines: use in primary care

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.

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North of Tyne anti-platelet guidelines: use in primary care

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  1. North of Tyne anti-platelet guidelines: use in primary care Jane S Skinner Consultant Community Cardiologist

  2. 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

  3. Which anti-platelet agents are prescribed in primary care? • Aspirin • Thienopyridines • Clopidogrel • Prasugrel • Dipyridamole

  4. 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

  5. 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

  6. Absolute effects of anti-platelet therapy on vascular events 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) 25 Placebo 20 Anti-platelet 15 Adjusted % vascular events 21.4% 10 17.0% 14.2% 10.2% 13.5% 17.8% 9.1% 10.4% 5 8.2% 8.1% 0 Previous MI Acute MI Previous stroke/TIA Acute stroke Other high risk ATC BMJ 2002;324:71

  7. 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

  8. 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

  9. Recurrent GI bleeding; aspirin plus PPI vs clopidogrel 10 Aspirin 80mg od plus esomeprazole 20mg bd (n=159) Probability of recurrent bleeding at 12 months (%) Clopidogrel 75mg od plus placebo (n=161) 8 6 4 2 0 Recurrent ulcer bleeding Lower GI bleeding NEJM 2005;352:238-44

  10. 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

  11. Combination anti-platelet agents • Aspirin plus thienopyridine • Clopidogrel • Prasugrel • Aspirin plus dipyridamole

  12. PLATELET ACTIVATION Cyclo-oxygense ASPIRIN Other sources Eg damaged endothelium Plaque rupture ADP RELEASE ADP RELEASE ADP RELEASE PLATELETADP RECEPTOR THIENOPYRIDINE PLATELET AGGREGATION

  13. Groups to consider • Coronary artery disease • Cerebrovascular disease • After a recent acute vascular event • After intervention

  14. 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

  15. 0.14 11.4% Placebo + ASA 0.12 9.3% 0.10 0.08 Clopidogrel + ASA Cumulative Hazard Rate 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 Aspirin vs aspirin plus clopidogrel in ACS without ST elevation Δ2.1% Excess of 1 life-threatening and 6 major bleeds per 1000 patients treated with clopidogrel NEJM 2001;345:494

  16. 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

  17. 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

  18. TITAN TRITON-TIMI 38 15 Clopidogrel HR 0.81(0.73-0.90)P=0.0004 1o EP: CV Death / MI / Stroke 12.1 9.9 10 Prasugrel Endpoint (%) 5 TIMI Major NonCABG Bleeds Prasugrel 2.4 HR 1.32(1.03-1.68)P=0.03 1.8 Clopidogrel 0 0 90 180 270 360 450 Days Wiviott et al., NEJM 2007; 357: 2001-5

  19. Aspirin vs aspirin and clopidogrel in stable patients Primary Efficacy Outcome = MI, Stroke, or CV Death) Median follow up 28 mths Moderate bleeding 2.1% clopidogrel vs 1.3% placebo Initiation of combination treatment with aspirin and clopidogrel is not recommended in stable patients with vascular disease p=0.22 CHARISMA New Engl J Med 2006;354

  20. MHRA Drug Safety Update July 2009 MHRA Drug Safety Update April 2010

  21. MHRA Drug safety update April 2010

  22. O’Donoghie et al. Lancet 2009;374:989-997

  23. Primary endpoint stratified by use of PPI PPI use at randomization (n= 4529) Clopidogrel Prasugrel CV death, MI or stroke 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 Days O’Donoghie et al. Lancet 2009;374:989-997

  24. 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

  25. 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

  26. 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

  27. ESPRIT main results ESPRIT Lancet 2006;367:1665-73

  28. 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

  29. MATCH Lancet 2004;364:331-337

  30. 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

  31. 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

  32. 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

  33. ATT collaboration. Lancet 2009;373:1849-60

  34. ATT collaboration. Lancet 2009;373:1849-60

  35. 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

  36. 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

  37. 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

  38. 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

  39. Summary • Anti-platelet agents for prevention in patients with or at risk of vascular disease • Indications • Risks • Single agents • Combination agents

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