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

The NICE ACS Guidelines: variation on an ESC theme? The NICE ACS Guidelines:

variation on an ESC theme?

Rob Henderson

Consultant Cardiologist

Trent Cardiac Centre

Nottingham University Hospitals

Rob Henderson

Consultant Cardiologist

Trent Cardiac Centre

Nottingham University Hospitals

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)

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)

UA/NSTEMI Guidance fromESC and NICE

UA/NSTEMI Guidance fromESC and NICE

ESC Guidance NICE Guidance

Publication June 2007 Pre-publication draftPublication March 2010

DevelopmentMultinational Taskforce of cardiologists

Multidisciplinary teamclinicians, information scientists, health economists, patient representatives

Perspective Clinical efficacyClinical EfficacyCost Efficacy Patient

Target Multinational, Europe NHS in England & Wales

NICE UA/NSTEMI GuidelineDevelopment Group 2008-2009


John Camm, chairHuon Gray, clinical advisor, NCGCSotiris Antoniou, pharmacistLina Bakhshi, information scientistJenny Cadman, nurseEmily Crowe, research fellowMark de Belder, cardiologistJose Diaz, research fellowDavid H. Geldard, patient repRob Henderson, cardiologistMarjan Jahangiri, cardiac surgeonTaryn Krause, project managerKate Lovibond, health economistGavin Maxwell, patient repFrancis Morris, A&E physicianAlun Roebuck, nurse consultantNicola Sloan, research fellowClaire Turner, project managerRichard Underwood, cardiac imagingMark Whitbread, paramedic





359 pages36 recommendations

NICE Guideline - Risk AssessmentNICE 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)

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)

Troponin status and in-hospital mortalityas function of GRACE risk score

Troponin status and in-hospital mortalityas function of GRACE risk score

Steg et al, Am J Med 2009;122:107Steg et al, Am J Med 2009;122:107

GRACE risk score (Granger algorithm)GRACE risk score (Granger algorithm)

N=27406 non-ST-elevation ACSN=27406 non-ST-elevation ACS

Troponin positive (red bars)Troponin negative (yellow bars)In-hosp mortality (blue line)

Troponin positive (red bars)Troponin negative (yellow bars)In-hosp mortality (blue line)

00

500500

15001500

20002000

25002500

30003000

35003500

10001000

0%0%

10%10%

20%20%

30%30%

40%40%

<51<51 6666 8585 105105 125125 145145 165165 185185 205205 225225 >226>2265656 7676 9595 115115 135135 155155 175175 195195 215215

Num

ber

of p

atie

nts

Num

ber

of p

atie

nts

In-h

ospi

tal m

orta

lity

(%)

In-h

ospi

tal m

orta

lity

(%)

NICE Guideline - Risk CategoriesNICE Guideline - Risk Categories

Risk category

% of ACS population*

Guideline risk categories and predicted six-month mortality

1a 12.5% Lowest 1.5% or below

1b 12.5% Low >1.5% to 3.0%

2a 12.5% Intermediate >3.0% to 6.0%

2b 12.5% High >6.0% to 9.0%

3 & 4 50.0% Highest Over 9%

*estimated from MINAP registry

R5 Use predicted 6-month mortality to categorise the risk of future adverse cardiovascular events:

R5 Use predicted 6-month mortality to categorise the risk of future adverse cardiovascular events:

NICE Guideline - ClopidogrelNICE 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)

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 patientsIn CURRENT double dose prevented 6 MI’s and 7 stent thromboses with excess of 3 extra major bleeds per 1000 PCI patients

NICE Guideline - FondaparinuxNICE 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)

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)

OASIS 5 - Fondaparinux vs Enoxaparin in Non-ST-elevation Acute Coronary Syndromes


5.8%

2.2%

7.3%

0.9%

5.7%

4.1%

9.0%

0.4%

0%

2%

4%

6%

8%

10%

Death/MI/refractoryischaemia

Major bleeding Composite: netbenefit

Catheter relatedthrombus

Fondarinux (n=10 057)

Enoxaparin (n=10 021)

OASIS 5 investigators NEJM 2006;354:1464OASIS 5 investigators NEJM 2006;354:1464Fondarinux 2.5mg sc odEnoxaparin 1mg/kg sc bdFondarinux 2.5mg sc odEnoxaparin 1mg/kg sc bd

Non-inferiorityP=0.007

Non-inferiorityP=0.007 P<0.001P<0.001

P<0.001P<0.001

P<0. 001P<0. 001

Events at 9 days

UFH/LMWH but not Fonda inhibits contact activation pathway (FXII, XI)

Cumulative mortalityCumulative mortality

180180303000 6060 9090 150150120120

0.040.04

0.000.00

0.020.02

0.060.06

Fondarinux n=10,021Enoxaparin n=10,057Fondarinux n=10,021Enoxaparin n=10,057

OASIS 5 Investigators, NEJM 2006;354:1464OASIS 5 Investigators, NEJM 2006;354:1464



6.5%6.5%

5.8%5.8%

Hazard ratio 0.89 (95% CI 0.80–1.00) P=0.05

Hazard ratio 0.89 (95% CI 0.80–1.00) P=0.05C

umul

ativ

e m

orta

lity

Cum

ulat

ive

mor

talit

y

NICE Guideline - Glycoprotein Inhibitors

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)

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)

Upstream GPI in non-ST-elevation ACSMeta-analysis of ACUITY-TIMING & Early-ACS

Upstream GPI in non-ST-elevation ACSMeta-analysis of ACUITY-TIMING & Early-ACS

0 1 2Favours early GPI

Favours early GPI

Favours delayed GPI

Favours delayed GPI

Odds Ratio (95% CI)Odds Ratio (95% CI)Endpoint at 30 days

MI

Death

D/MI/Unplanned revasc

Unplanned revasc

Major bleed

Draft NICE guideline document Draft NICE guideline document

N=14009Thienopyridine use 64% in ACUITY, 75% in Early-ACS

Early GPI Delayed GPI

7.8% 8.8%

2.4% 2.2%

10.7% 11.8%

2.3% 2.8%

2.4% 1.8%

NICE Guideline - BivalirudinNICE 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)

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)

ACUITY – bivalirudin vs heparin & IIb/IIIa blocker in non-ST elevation ACS patients scheduled for invasive strategy

ACUITY – bivalirudin vs heparin & IIb/IIIa blocker in non-ST elevation ACS patients scheduled for invasive strategy

7.3%

5.7%

11.7%

7.7%

5.3%

11.8%

7.8%

3.0%

10.1%

0%

2%

4%

6%

8%

10%

12%

14%

MACE* Major bleed Net clinical outcome

UFH/Enox & GPIIbIIIa (n=4603)

Bivalirudin &GPIIbIIIa (n=4604)

Bivalirudin (n=4612)

Stone, NEJM 2006;355:2203Stone, NEJM 2006;355:2203

All patients scheduled for coronary arteriography/PCI <72hBivalirudin 0.1mk/kg bolus, 0.25mg/kg/hr infusion*Death, MI, revasc for ischaemia

All patients scheduled for coronary arteriography/PCI <72hBivalirudin 0.1mk/kg bolus, 0.25mg/kg/hr infusion*Death, MI, revasc for ischaemia

NSNS P<0.001P<0.001 P=0.015P=0.015

30 d outcomes

NICE Guideline - Invasive strategyNICE 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)

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)

ConclusionsConclusions

• 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

• 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

Documents

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