The NICE ACS Guidelines: variation on an ESC theme?

1. The NICE ACS Guidelines: variation on an ESC theme? Rob Henderson Consultant Cardiologist Trent Cardiac Centre Nottingham University Hospitals

2. MY CONFLICTS OF INTEREST ARE Member, NICE ACS Guideline Development Group Advisory Boards and Speaker Honoraria (Pfizer, Lilly UK, Daiichi-Sankyo UK Ltd, Boston Scientific, Cordis UK, Abbott Vascular)

3. UA/NSTEMI Guidance fromESC and NICE

4. NICE UA/NSTEMI Guideline Development Group 2008-2009 John Camm, chair Huon Gray, clinical advisor, NCGC Sotiris Antoniou, pharmacist Lina Bakhshi, information scientist Jenny Cadman, nurse Emily Crowe, research fellow Mark de Belder, cardiologist Jose Diaz, research fellow David H. Geldard, patient rep Rob Henderson, cardiologist Marjan Jahangiri, cardiac surgeon Taryn Krause, project manager Kate Lovibond, health economist Gavin Maxwell, patient rep Francis Morris, A&E physician Alun Roebuck, nurse consultant Nicola Sloan, research fellow Claire Turner, project manager Richard Underwood, cardiac imaging Mark Whitbread, paramedic

5. NICE UA/NSTEMI Guideline Development Group2008-2009 John Camm, chair Huon Gray, clinical advisor, NCGC Sotiris Antoniou, pharmacist Lina Bakhshi, information scientist Jenny Cadman, nurse Emily Crowe, research fellow Mark de Belder, cardiologist Jose Diaz, research fellow David H. Geldard, patient rep Rob Henderson, cardiologist Marjan Jahangiri, cardiac surgeon Taryn Krause, project manager Kate Lovibond, health economist Gavin Maxwell, patient rep Francis Morris, A&E physician Alun Roebuck, nurse consultant Nicola Sloan, research fellow Claire Turner, project manager Richard Underwood, cardiac imaging Mark Whitbread, paramedic 359 pages 36 recommendations

6. NICE Guideline - Risk Assessment R1 Formally assess individual risk of future adverse cardiovascular events using an established risk scoring system that predicts 6-month mortality (e.g. GRACE) (Observational studies)

7. Troponin status and in-hospital mortalityas function of GRACE risk score 3500 40% Troponin positive (red bars) Troponin negative (yellow bars) In-hosp mortality (blue line) 3000 30% 2500 2000 Number of patients 20% In-hospital mortality (%) 1500 1000 10% 500 0 0% >226 <51 56 66 76 85 95 105 115 125 135 145 155 165 175 185 195 205 215 225 GRACE risk score (Granger algorithm) N=27406 non-ST-elevation ACS Steg et al, Am J Med 2009;122:107

8. NICE Guideline - Risk Categories R5 Use predicted 6-month mortality to categorise the risk of future adverse cardiovascular events: *estimated from MINAP registry

9. NICE Guideline - Clopidogrel R9 Offer 300mg loading dose of clopidogrel in addition to aspirin to patients with no contra-indications and predicted 6-month mortality >1.5% (CURE, CREDO, Cuisset, PRACTICAL) Emerging evidence for use of 600mg in PCI patients In CURRENT double dose prevented 6 MI’s and 7 stent thromboses with excess of 3 extra major bleeds per 1000 PCI patients

10. NICE Guideline - Fondaparinux R17 Offer fondaparinux to patients who do not have a high bleeding risk, unless coronary angiography is planned within 24 hours of admission (OASIS-5, cost effective with high certainty)

11. OASIS 5 - Fondaparinux vs Enoxaparin in Non-ST-elevation Acute Coronary Syndromes Events at 9 days UFH/LMWH but not Fonda inhibits contact activation pathway (FXII, XI) P<0.001 Non-inferiority P=0.007 P<0.001 P<0. 001 Fondarinux 2.5mg sc od Enoxaparin 1mg/kg sc bd OASIS 5 investigators NEJM 2006;354:1464

12. OASIS 5 - Fondaparinux vs Enoxaparin in Non-ST-elevation Acute Coronary Syndromes 0.06 0.04 0.02 0.00 0 60 90 120 150 180 30 Fondarinux n=10,021 Enoxaparin n=10,057 Cumulative mortality 6.5% 5.8% Cumulative mortality Hazard ratio 0.89 (95% CI 0.80–1.00) P=0.05 OASIS 5 Investigators, NEJM 2006;354:1464

13. NICE Guideline - Glycoprotein Inhibitors R14 Consider iv eptifibatide or tirofiban as part of the early management of patients with predicted 6-month mortality >3%, and who are scheduled to undergo angiography within 96 hours of hospital admission R15 Consider abciximab as an adjunct to PCI for patients at intermediate or higher risk who are not already receiving a GPI or bivalirudin (Meta-analyses: Boersma, Roffi. New RCTs: ISAR-REACT-2, ELISA-2, ACUITY-TIMING, Early-ACS, high uncertainty in cost effectiveness modeling)

14. Upstream GPI in non-ST-elevation ACS Meta-analysis of ACUITY-TIMING & Early-ACS Odds Ratio (95% CI) Favours early GPI Favours delayed GPI N=14009 Thienopyridine use 64% in ACUITY, 75% in Early-ACS Draft NICE guideline document

15. NICE Guideline - Bivalirudin R22 Consider switching to bivalirudin, rather than adding a GPI to an alternative antithrombin, for patients: • with predicted 6-month mortality >3% and • are not already receiving a GPI or fondaparinux and • are scheduled to undergo angiography within 24 hrs (ACUITY, REPLACE-2, cost effective with high uncertainty)

16. ACUITY – bivalirudin vs heparin & IIb/IIIa blocker in non-ST elevation ACS patients scheduled for invasive strategy 30 d outcomes P<0.001 P=0.015 NS All patients scheduled for coronary arteriography/PCI <72h Bivalirudin 0.1mk/kg bolus, 0.25mg/kg/hr infusion *Death, MI, revasc for ischaemia Stone, NEJM 2006;355:2203

17. NICE Guideline - Invasive strategy R24 Offer coronary angiography (and follow-on PCI) within 96 hrs of admission to patients with predicted 6-month mortality >3.0% if they have no contraindications (active bleeding, comorbidity). Perform angiography as soon as possible for patients who are clinically unstable or at high ischaemic risk R25 Offer coronary angiography to patients with low risk if ischaemia is subsequently experienced or demonstrated (High Quality RCTs, meta-analyses)

18. Conclusions • NICE Guideline provides clinical guidance for effective & cost-effective treatment of UA/NSTEMI • Potentially important differences between ESC and NICE Guidance • NICE Guidance will change our approach to • risk stratification • anticoagulation • early invasive strategy • Due for final publication March 2010