Evidence -based Nuclear Cardiology: Imaging of CAD … fileEvidence -based Nuclear Cardiology: Imaging of CAD The NICE document Technical Meeting on: ... (exercise, pharmacologic)

EvidenceEvidence--based Nuclear Cardiology:based Nuclear Cardiology:Imaging of CADImaging of CAD

The NICE documentThe NICE document

Technical Meeting on:Technical Meeting on:““Current Role of Nuclear Cardiology in the Current Role of Nuclear Cardiology in the

Management of Cardiac DiseasesManagement of Cardiac Diseases””Vienna, 5Vienna, 5--9 May 20089 May 2008

Vienna International CentreVienna International Centre

Myocardial Perfusion Myocardial Perfusion ScintigraphyScintigraphy (MPS) (MPS) for the Diagnosis and Management of for the Diagnosis and Management of Angina and Myocardial InfarctionAngina and Myocardial InfarctionTechnology Appraisal Guidance 73Technology Appraisal Guidance 73Issue date: November 2003Issue date: November 2003Review date: November 2006Review date: November 2006

www.nice.org.uk/TA073guidancewww.nice.org.uk/TA073guidance

About NICEAbout NICE�� Who they areWho they areThe National Institute for Health and Clinical Excellence (NICE)The National Institute for Health and Clinical Excellence (NICE) is an independent is an independent organization responsible for organization responsible for providing national guidanceproviding national guidance on the promotion of good on the promotion of good health and the prevention and treatment of diseases.health and the prevention and treatment of diseases.�� What they doWhat they doNICE produces guidance in three areas of health:NICE produces guidance in three areas of health:

•• Public healthPublic health -- guidance on the promotion of good health and the prevention of guidance on the promotion of good health and the prevention of diseases. diseases. •• Health technologiesHealth technologies -- guidance on the use of new and existing medicines, guidance on the use of new and existing medicines, treatments and procedures. treatments and procedures. •• Clinical practiceClinical practice -- guidance on the appropriate treatment and care of people with guidance on the appropriate treatment and care of people with specific diseases and conditions.specific diseases and conditions.

�� How they workHow they workNICE guidance is developed using the expertise of the NHS and thNICE guidance is developed using the expertise of the NHS and the wider healthcare e wider healthcare community including NHS staff, healthcare professionals, patientcommunity including NHS staff, healthcare professionals, patients and carers, industry s and carers, industry and the academic world.and the academic world.

�� The The National Health ServiceNational Health Service ((NHSNHS)) is the publicly funded healthcareis the publicly funded healthcaresystem in the UK. The NHS provides the majority of healthcarsystem in the UK. The NHS provides the majority of healthcare ine inEngland, and came into effect in 1948. England, and came into effect in 1948. �� The UK government department responsible for the NHS is theThe UK government department responsible for the NHS is theDepartment of Health, headed by the Health Secretary.Department of Health, headed by the Health Secretary.�� The NHS is largely funded from general taxation. Most of theThe NHS is largely funded from general taxation. Most of theexpenditure of the Department of Health (USD 200 billion in expenditure of the Department of Health (USD 200 billion in 20082008--9) is9) isspent on the NHS, equivalent to about 9% of GDP.spent on the NHS, equivalent to about 9% of GDP.�� The NHS is the world's largest health service and the world's fThe NHS is the world's largest health service and the world's fourthourth--largest employer.largest employer.

About NHSAbout NHS

Health expenses in EuropeHealth expenses in EuropeSource: CEA Statistics No. 30, May 2007Source: CEA Statistics No. 30, May 2007




Where is Nuclear Cardiology performed?Where is Nuclear Cardiology performed?Source: European Council of Nuclear Cardiology, June 2006Source: European Council of Nuclear Cardiology, June 2006

By whom is Nuclear Cardiology performed?By whom is Nuclear Cardiology performed?Source: European Council of Nuclear Cardiology, June 2006Source: European Council of Nuclear Cardiology, June 2006

�� Standing advisory committee of the Standing advisory committee of the NICE.NICE.�� Composed by clinical professors, academics, generalComposed by clinical professors, academics, generalpractitioners, scientists, biostatisticians, health economispractitioners, scientists, biostatisticians, health economists, etc.ts, etc.�� The total number of members is > 20.The total number of members is > 20.�� Each Committee member is asked to disclose any conflict ofEach Committee member is asked to disclose any conflict ofinterests regarding the technology to be appraised, and is exinterests regarding the technology to be appraised, and is excludedcludedif necessary.if necessary.�� Each appraisal of a technology is assigned to a Health TechnoloEach appraisal of a technology is assigned to a Health TechnologygyAnalyst and a Project Manager within the Institute. Analyst and a Project Manager within the Institute.

Appraisal Committee membersAppraisal Committee members

�� Assessment Report by the Health Services Research Unit in Assessment Report by the Health Services Research Unit in collaboration with:collaboration with:•• Health Economics Research Unit, Health Economics Research Unit, DptDpt. of Public Health. of Public Health•• University of AberdeenUniversity of Aberdeen•• Grampian University Hospitals NHS TrustGrampian University Hospitals NHS Trust

�� Manufacturers / commercial companies:Manufacturers / commercial companies:•• Amersham, Ashby, Amersham, Ashby, BartecBartec, Bristol, Bristol--Myers, GE, Philips, Siemens, Tyco.Myers, GE, Philips, Siemens, Tyco.

�� Institutions / professional associations / carer groups:Institutions / professional associations / carer groups:•• Dept. of Health, British Cardiac Society, British Nuclear CardiDept. of Health, British Cardiac Society, British Nuclear CardiologyologySociety, British Nuclear Medicine Society, Royal College of PSociety, British Nuclear Medicine Society, Royal College of Physicians,hysicians,Royal College of Radiologists, etc.Royal College of Radiologists, etc.

�� Commentator organizations:Commentator organizations:•• Cochrane Heart Group, Institute of Nuclear Medicine, Inst. of PCochrane Heart Group, Institute of Nuclear Medicine, Inst. of Physicshysicsand Engineering in Medicine, NHS Information Authority, etc.and Engineering in Medicine, NHS Information Authority, etc.

�� Expert individualsExpert individuals

Sources of evidence Sources of evidence considered by the Committeeconsidered by the Committee

1. Guidance1. Guidance

�� ------------------------

� ……………………….

� ……………………….

� ------------------------

� ……………………….

� ……………………….

� ------------------------

� ……………………….

� ……………………….

??

2. Clinical need and practice2. Clinical need and practice�� CAD is the commonest cause of death in the UK.CAD is the commonest cause of death in the UK.�� Angina, MI and sudden cardiac death are the most commonAngina, MI and sudden cardiac death are the most commonmanifestations of CAD.manifestations of CAD.�� About 2.65 million people in the UK have CAD (335,000 newAbout 2.65 million people in the UK have CAD (335,000 newcases/year).cases/year).�� Total cost to the NHS about USD 3.4 billion/year.Total cost to the NHS about USD 3.4 billion/year.�� Coronary angiography (CA) is the gold standard but findings areCoronary angiography (CA) is the gold standard but findings arenot always a reliable indicator of the functional significancnot always a reliable indicator of the functional significance of ae of acoronary coronary stenosisstenosis..�� Routine use of CA without prior nonRoutine use of CA without prior non--invasive testing is notinvasive testing is notadvisable because of high cost and associated advisable because of high cost and associated mobiditymobidity andandmortality (0.1mortality (0.1--0.2%).0.2%).�� NonNon--invasive techniques include invasive techniques include sECGsECG, echocardiography, MPS,, echocardiography, MPS,MRI and PET.MRI and PET.

3. The technology3. The technology

�� IV injection of tracer (IV injection of tracer (201201Tl, Tl, 99m99mTcTc--MIBI, MIBI, 99m99mTcTc--TETRO) during stressTETRO) during stress(exercise, pharmacologic) and rest.(exercise, pharmacologic) and rest.

�� SPECT is the clinical standard SPECT is the clinical standard –– planar not acceptable.planar not acceptable.

�� Uptake patterns: homogeneous, reversible, nonUptake patterns: homogeneous, reversible, non--reversible, mixed.reversible, mixed.

�� Technical improvements: AC, gating.Technical improvements: AC, gating.

�� Complication rates (=stress): morbidity Complication rates (=stress): morbidity ~~ 0.02%, mortality 0.02%, mortality ~~ 0.01%.0.01%.

�� Radiation exposure Radiation exposure ~ coronary angiography.~ coronary angiography.

�� Cost (NHS reference): Cost (NHS reference): ~~ USD 500 vs. USD 500 vs. sECGsECG USD 200, CA USD 2,200.USD 200, CA USD 2,200.

4. Evidence and interpretation4. Evidence and interpretation

�� Clinical effectivenessClinical effectiveness�� Diagnostic performanceDiagnostic performance (83 studies) (*)(83 studies) (*)•• SPECT MPS vs. SPECT MPS vs. sECGsECG (CA gold standard, 21 studies):(CA gold standard, 21 studies):

Sensitivity 81% (63Sensitivity 81% (63--93%) vs. 65% (4293%) vs. 65% (42--92%) 92%) Specificity 65% (10Specificity 65% (10--90%) vs. 67% (4190%) vs. 67% (41--88%) 88%)

•• SPECT MPS only (CA gold standard, 62 studies):SPECT MPS only (CA gold standard, 62 studies):Sensitivity 86%Sensitivity 86%Specificity 74%Specificity 74%

(*) ACC/AHA Task Force Guideline:(*) ACC/AHA Task Force Guideline:Specificity 89Specificity 89--90%90%Specificity 70Specificity 70--76% 76%


�� Clinical effectivenessClinical effectiveness�� Diagnostic performanceDiagnostic performance�� Long term prognostic valueLong term prognostic value (46 studies)(46 studies)•• Annual cardiac event rate (*)Annual cardiac event rate (*)

MPS abnormal: 6.7%MPS abnormal: 6.7%MPS normal: 0.7%MPS normal: 0.7%

(*) Meta(*) Meta--analyses of 15,000 and 20,963 pts. respectivelyanalyses of 15,000 and 20,963 pts. respectively


�� Clinical effectivenessClinical effectiveness�� Diagnostic performanceDiagnostic performance�� Long term prognostic valueLong term prognostic value (46 studies)(46 studies)•• Proportion of normal angiograms (*)Proportion of normal angiograms (*)

With previous MPS: 18 With previous MPS: 18 -- 33%33%With no previous MPS: 33 With no previous MPS: 33 -- 43%43%

(*) 2 studies (*) 2 studies –– not pooled not pooled –– 6,800 and 4,688 pts. respectively)6,800 and 4,688 pts. respectively)


�� Clinical effectivenessClinical effectiveness�� Diagnostic performanceDiagnostic performance�� Long term prognostic valueLong term prognostic value (46 studies)(46 studies)•• Rate of subsequent revascularization (*)Rate of subsequent revascularization (*)

MPSMPS--CA strategy: 13 CA strategy: 13 -- 27%27%Direct CA strategy: 16 Direct CA strategy: 16 -- 44%44%

(*) 3 studies (*) 3 studies –– pooled data pooled data –– approx. 11,000 pts.)approx. 11,000 pts.)


�� Clinical effectivenessClinical effectiveness�� Diagnostic performanceDiagnostic performance�� Long term prognostic valueLong term prognostic value (46 studies)(46 studies)•• Extent and sizeExtent and size of perfusion defects predict the likelihoodof perfusion defects predict the likelihoodof future cardiac events.of future cardiac events.•• MPS provides MPS provides independent and incrementalindependent and incremental prognosticprognosticinformation that helps to riskinformation that helps to risk--stratify patients and influencestratify patients and influencethe way in which they are managed.the way in which they are managed.•• This also applies for This also applies for special subspecial sub--groupsgroups::

•• women women •• diabetics diabetics •• postpost--MI MI •• postpost--revascularizationrevascularization•• medically treatedmedically treated•• hospitalized w/ angina.hospitalized w/ angina.


�� Cost effectivenessCost effectiveness�� ModellingModelling•• Decision tree models (for diagnostic performance)Decision tree models (for diagnostic performance)•• Markov models (long term costs and benefits)Markov models (long term costs and benefits)

Hypothetical cohort: 1,000 pts.Hypothetical cohort: 1,000 pts.Starting age: 60.Starting age: 60.Assumed effectiveness of therapy: 10 yrs.Assumed effectiveness of therapy: 10 yrs.Time horizon: 25 yrs. Time horizon: 25 yrs.


�� Cost effectivenessCost effectiveness�� ModellingModelling�� Diagnostic strategiesDiagnostic strategies•• sECGsECG→→ MPS MPS →→ CACA•• sECGsECG→→ CACA•• MPS MPS →→ CACA•• CACA


�� Cost effectivenessCost effectiveness�� ModellingModelling�� Diagnostic strategiesDiagnostic strategies�� Presented as incremental cost:Presented as incremental cost:•• per trueper true--positive diagnosedpositive diagnosed•• per accurate diagnosisper accurate diagnosis•• per life year gainedper life year gained•• per qualityper quality--adjusted life year adjusted life year (QALY*)(QALY*) gainedgained•• for different levels of prevalence of CADfor different levels of prevalence of CAD

(*) QALY = quality(*) QALY = quality--adjusted life year (score is 0adjusted life year (score is 0––1 per year)1 per year)


�� Cost effectivenessCost effectiveness�� ModellingModelling�� Diagnostic strategiesDiagnostic strategies�� Presented as incremental costPresented as incremental cost�� Results:Results:•• As prevalence of CAD increased, total cost increased andAs prevalence of CAD increased, total cost increased andtotal # of total # of QALYsQALYs gained decreased for each strategy.gained decreased for each strategy.•• MPS MPS →→ CA strategyCA strategy has better has better ICERsICERs(*)(*) at at low levelslow levels ofofprevalence of CAD.prevalence of CAD.•• sECGsECG →→ CACA and and direct CAdirect CA strategies have better strategies have better ICERsICERs atathigherhigher prevalence levels.prevalence levels.

(*) (*) ICER = incremental costICER = incremental cost--effectiveness ratio = effectiveness ratio = Ratio of the change in costs of an intervention (compared to theRatio of the change in costs of an intervention (compared to the alternative) to alternative) to the change in effects of the intervention.the change in effects of the intervention.


�� Consideration of the evidenceConsideration of the evidence

�� Uncertainty remains on true values for Uncertainty remains on true values for SenSen & & EspEsp for MPS.for MPS.�� MPS value depends on the MPS value depends on the likelihood of CADlikelihood of CAD in the targetin the target

population.population.�� MPS is MPS is costcost--effectiveeffective across a wide range of clinical situations.across a wide range of clinical situations.�� MPS influences pts. MPS influences pts. management management (i.e., enabling redirection into(i.e., enabling redirection into

medical rather than surgical treatment).medical rather than surgical treatment).�� Increased Increased availability and provisionavailability and provision of MPS within the NHS isof MPS within the NHS is

desirable on the basis of this evidence.desirable on the basis of this evidence.�� Increased use of MPS should initially be targeted at groups forIncreased use of MPS should initially be targeted at groups for

whom it provides the whom it provides the greatest benefitgreatest benefit in costin cost--effectiveness. effectiveness.

5. Recommendations for further research5. Recommendations for further research�� Further research is recommended in pts. with known CAD Further research is recommended in pts. with known CAD regarding the value of MPI relative to other procedures such as:regarding the value of MPI relative to other procedures such as:�� EchocardiographyEchocardiography�� Magnetic Resonance ImagingMagnetic Resonance Imaging�� Computed TomographyComputed Tomography�� PET & PET/CTPET & PET/CT

�� Utilization of Nuclear Cardiology in the UK (British NuclearUtilization of Nuclear Cardiology in the UK (British NuclearCardiology Society, 2000):Cardiology Society, 2000):�� 1200 scans / million population / year.1200 scans / million population / year.�� Average waiting time: 20 weeks.Average waiting time: 20 weeks.

�� Estimated optimal level:Estimated optimal level:�� 4000 scans / million / year.4000 scans / million / year.�� Average waiting time: 6 wks. routine, 1 wk. urgent.Average waiting time: 6 wks. routine, 1 wk. urgent.

�� Needs:Needs:�� 73 additional gamma cameras.73 additional gamma cameras.�� Training.Training.

6. Implications for the NHS6. Implications for the NHS

7. Final Guidance7. Final Guidance

�� MPS using SPECTMPS using SPECT is recommended for the is recommended for the diagnosisdiagnosis of of suspected CAD:suspected CAD:�� As the As the initial diagnostic toolinitial diagnostic tool when treadmill exercise is difficult orwhen treadmill exercise is difficult orimpossible, and when stress echo is of low sensitivity or dimpossible, and when stress echo is of low sensitivity or difficultifficultto interpret (LBBB, women, diabetics).to interpret (LBBB, women, diabetics).

�� As As part of investigational strategypart of investigational strategy in pts. with low to intermediatein pts. with low to intermediatelikelihood of CAD. likelihood of CAD.

�� MPS using SPECTMPS using SPECT is recommended as part of theis recommended as part of theinvestigational strategy in the investigational strategy in the managementmanagement of establishedof establishedCAD:CAD:�� In patients who remain In patients who remain symptomaticsymptomatic following following MIMI oror

reperfusion interventions. reperfusion interventions.

8. Implementation and audit8. Implementation and audit

�� NHS hospitals and clinicians should NHS hospitals and clinicians should take account of the guidance.take account of the guidance.�� Local guidelines or care pathways for CAD patients shouldLocal guidelines or care pathways for CAD patients shouldincorporate the guidance.incorporate the guidance.�� Audits on MPSAudits on MPS could be carried out to ensure that the technique iscould be carried out to ensure that the technique isused appropriately.used appropriately.�� Audits on patient managementAudits on patient management (pts. referred for investigation of (pts. referred for investigation of suspected CAD, pts. with known CAD symptomatic following MI, suspected CAD, pts. with known CAD symptomatic following MI, CABG or PTCA. CABG or PTCA.

8. Implementation and audit8. Implementation and audit

�� Calculation of Compliance with guidance (%):Calculation of Compliance with guidance (%):

No. of pts. whose care is consistent with the criterion No. of pts. whose care is consistent with the criterion ++

No. of pts. who meet any exception listedNo. of pts. who meet any exception listed

No. of pts. to whom the measure appliesNo. of pts. to whom the measure applies

8. Review of guidance8. Review of guidance

�� The The Review DateReview Date for a Technology Appraisal is when for a Technology Appraisal is when the Guidance Executive will consider any new evidence the Guidance Executive will consider any new evidence in the form of an in the form of an Updated ReportUpdated Report and decide whether the and decide whether the technology should be referred to the Appraisal technology should be referred to the Appraisal Committee for review.Committee for review.

�� This guidance was reviewed in This guidance was reviewed in November 2006. November 2006.

9. Upcoming guidance9. Upcoming guidance

�� Acute coronary syndromes.Acute coronary syndromes.�� Acute chest pain.Acute chest pain.�� Stable angina.Stable angina.�� CT coronary angiography. CT coronary angiography.

Thank you…

Documents

Evidence -based Nuclear Cardiology: Imaging of CAD … fileEvidence -based Nuclear Cardiology: Imaging of CAD The NICE document Technical Meeting on: ... (exercise, pharmacologic)