Transcript Angina – A Pain physician`s perspective

Refractory Angina
Clinical and Cost
effectiveness
Dr Simon Thomson
Consultant in pain medicine
Basildon and Thurrock University Trust
President of INS
Disclosures
Honoraria and expenses

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Codman
Pfizer
ECMT
Background
The Aim of Treatment
The primary aim of therapy is to maximise
the patients quality of life by ameliorating
the effects of the condition without
jeopardising quantity of life.
Daily Mail 27th September 2010
Me and My Operation: The Remote control that
switches off Angina Pain
SCS and Angina pectoris
Evidence of clinical efficacy of SCS in
angina
Mechanisms of action from animal and
human data
Patient population with angina who have
unmet need
Limited understanding amongst referrers
Barriers
Reluctance to refer outside cardiology/CTS
Definition of RA not widely known
Missing elements of evidence base
Poorly developed care pathway
Multiple treatment options
Fears
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Safety
Palliative versus prognostic benefits of
revascularisation
New patient to angina clinic
Rehabilitation & Optimise risk factors & medication
ANGIOGRAPHY if indicated
Prognostic disease
Non-prognostic disease
LMS, Proximal 3VD, or Proximal
2VD that includes LAD
SVD, 2VD not including prox LAD,
distal disease, post revascularisation
Ensure that the patient has received rehabilitation, understands
his condition, is on optimal medication and still wants Rx
Select from:
TENS
SGB
Opioids
If new symptoms develop and
EECP
CABG
angiography shows new prognostic
SCS
disease
PTCA
PTCA
CABG
Laser etc, etc, etc
?
NICE Guidance
Spinal cord stimulation is recommended as a treatment
option for adults with chronic pain of neuropathic origin
who:


continue to experience chronic pain (measuring at least 50 mm on a 0–100 mm visual
analogue scale) for at least 6 months despite appropriate conventional medical
management, and
who have had a successful trial of stimulation as part of the assessment specified in
recommendation 1.3
Spinal cord stimulation is not recommended as a
treatment option for adults with chronic pain of ischaemic
origin except in the context of research as part of a
clinical trial. Such research should be designed to
generate robust evidence about the benefits of spinal
cord stimulation (including pain relief, functional
outcomes and quality of life) compared with standard
care.
Strategy
NSUKI research group
National effectiveness study
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Collaborative - include cardiology
Public funded SCS project
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NIHR
Pilot study
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RfPB
Programme grant
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National
Efficacy vs Effectiveness
 Effectiveness
 Efficacy
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explanatory trials
highly selected
populations
comparator: often
placebo
A vs B
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outcomes: clinical, often
surrogates, adverse
effects
‘is the therapy effective’
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pragmatic trials
few exclusions
comparator: ‘current (best)
practice’
Therapy added to best
practice and compared to
best practice alone
A+B vs B
outcomes: patient-focused,
down-stream resources
‘real world added value’
Taylor R.S. Value in Health 2001;4:8-11
Health Technology Development
Basic
biomedical
research
Phase I studies
Safety &
efficacy
Phase II/III trials
Licensing
Effectiveness and
cost-effectiveness
General clinical
use
Phase IV trials
Reimbursement
Quality Adjusted Life Years (QALYs)
 Cost per QALY used increasingly by central decision making
bodies
 Utility reflects an individual’s preference for a particular state of
well being derived from the consumption of healthcare
 Approaches to deriving utility values includes

Preference Based (i.e.,VAS)

Widely used scales include the EQ-5D and the SF-36
 Respondents place their current health status on an anchored
interval scale (0-1) from perfect health (1=perfect health) to death
with 0=death
Cost Effectiveness Analysis
Incremental cost effectiveness ratio (ICER)
ICER =
Cost [new technology – current care]
Outcome [new technology – current care]
i.e. additional cost per unit of health care gain
CEA Rationale Framework for
Decision Making
Cost
Difference
Max CE
Ratio (Rc)
DOMINANT
DON’T FUND
c
Effect Difference
DOMINANT
FUND
Cost Effectiveness Threshold
Inflexion B
Probability
of
Rejection
£25,000 - £35,000
Inflexion A
£5,000 - £15,000
Increasing (log) incremental cost-effectiveness
ratio
Study Selection
``
Author
(year)
Patient
N
Rx
Control
Primary
outcome
Follow
up
Quality
De Jongste
(1994)
22
SCS
No SCS
Exercise
capacity
2-mths
2/5
DiPede
(2001)
30
SCS ON
SCS OFF
Ischaemic
burden
48-hrs
3/5
EBSY
(1998)
104
SCS
CABG
Exercise
capacity.
Angina
symptoms
6-mths, 2yrs, 5-yrs
2/5
Hauvast
(1998)
25
SCS ON
SCS OFF
Exercise
capacity
1.5-mths
2/5
Jessurum
(1999)
24
SCS ON
SCS OFF
Exercise
capacity
1-mth
2/5
SpiRiT
(2006)
68
SCS
PMR
Exercise
capacity
3, 6, 12,
14-mths
4/5
Eddicks
(2007)
24
SCS ON
SCS OFF
Exercise
capacity
1-mth
4/5
Results
SCS outcomes were similar when
compared to CABG or PMR
SCS versus “No Stim”
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Improvements in all outcomes
Significant gains in exercise capacity
Decreased healthcare costs at 2 years vs
CABG
Why?
Spirit trial
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Better outcomes for QoL and survival in
second half of recruitment
ICER not favourable
ESBY
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Not Refractory angina
SCS as good as comparator for pain but not
ischaemic burden
ICER not favourable
Costs were comparative
SCS for RA
Cost per QALY @ 2-yr
SCS
(n=34)
Percutaneous
Difference
myocardial laser
revascularisation
(n=34)
Costs
£17,736
£12,215
+£5,520
QALYs
1.19
1.07
+0.12
ICER
£46,000 per QALY
Dyer (2008) BMC Trials [on line]
The Spirit Trial
For patients recruited during 2000/01, the ICER
was estimated at £230,000 per QALY (95% CI: £267,000 to £590,000)
For 2002/03, the ICER was estimated at
£18,000 per QALY (95% CI: -£21,000 to 51,000)
This improvement can largely be explained by
better outcomes, in terms of survival and QoL,
experienced by SCS patients in the second half
of the study
Dyer (2008) BMC Trials [on line]
Conclusions
SCS appears to be an effective and safe
treatment option in the management of
refractory angina patients and of similar
efficacy and safety to PMR, a potential
alternative treatment. Further high quality
RCT and cost effectiveness evidence is
needed before SCS can be accepted as a
routine treatment for refractory angina.
Invited National Meeting
December 20th 2008 Hilton Paddington
Invited meeting 25 invitations
19 attendees
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4 Cardiologists
8 Anaesthetists
1 Academic health service researcher
7 Industry representatives
NIHR RfPB Funded Project
(PB-PG-1208-18031)
Investigators
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CI: Sam Eldabe (Middlesborough)
Local PIs: Simon Thomson (Basildon), Jon
Raphael (Dudley)
Cardiologists: Mark deBelder (M/brough),
Rajesh Aggarwal (Basildon)
Health economist: Andrea Manca (York)
Statistician: Rod Taylor (Exeter)
NIHR RfPB Funded Project
(PB-PG-1208-18031)
Part 1 – UK Survey current management
of RA patients
the number of RA patients treated in the last 12-months
and details of their medical treatment
views of medical staff on the suitability of SCS as a
treatment option for RA
willingness to participate in a multicentre trial of SCS
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Part 2 – Pilot trial (RASCAL)
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Refractory Angina
Spinal Cord stimulation
usuAL care
Aims of Study
To assess recruitment, uptake and
retention of subjects in both groups
To assess the feasibility and acceptability
of SCS treatment from the point of view of
patients and referring physicians
To assess the feasibility and acceptability
of standardising usual care from the point
of view of patients and referring physicians
Aims of Study
To test the feasibility and acceptability of
the proposed trial outcome measures in
both groups
Results from this pilot study will inform the
design and power for a defintive
multicentre RCT
Population
Definitions of Refractory Angina
Refractory angina pectoris is a chronic condition
characterized by the presence of angina caused by
coronary insufficiency in the presence of coronary artery
disease which cannot be controlled by a combination of
medical therapy, angioplasty and coronary bypass
surgery. The presence of reversible myocardial
ischaemia should be clinically established to be the
cause of the symptoms. Chronic is defined as a duration
of more than 3 months
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Report from the European Society of Cardiology Joint Study
Group on the Treatment of Refractory Angina
European Heart Journal (2002) 23, 355–370
UK RA guideline group
definition
More pragmatic and practical definition for clinical use
Delay in diagnosis of RA prevented
Patient centred decision making
Chronic stable angina that persists despite optimal
medication and when revascularisation is unfeasible or
where the risks are unjustified
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Chester MG, et al
http://www.angina.org/?page_id=18 Accessed July 2010
Epidemiology of RA
Prevalence in UK
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Estimated 50,000 to78,000 by 2020
Incidence
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10,000 new cases per year
£2.5 billion on revascularisation over 10
years
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£1 billion of this spent on palliative procedures
Our population
RA as defined by one cardiologist and either
cardiologist or CTS
Other pain causes excluded by Pain physician
Inclusion
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Limiting angina CCS 3+ on optimal medical treatment
Angiographically documented CAD
Not suitable for revascularisation in opinion of referring
Satisfactory multidimensional pain assessment
Demonstrable ischaemia on functional testing
Our population
Exclusions
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Presence of pacemaker or implanted
defibrillator that is incompatible with SCS
Patient refusal to participate in the study
Presence of co morbidity considered by the
assessing clinician to overshadow the effect
of the angina
Poor cognitive ability
Ongoing anticoagulation therapy; where
anticoagulants cannot be safely discontinued
without jeopardising patient safety
Subjects and Randomisation
3 sites
45 patients
1:1 randomisation at PMT
SCS + UC vs UC alone
Intervention
Intervention
Add SCS to usual medical care and compare to
medical care alone A+B vs B
Centres can provide SCS (experienced) and
usual care
Treatments to start within 6 weeks of
randomisation
SCS + UC
Number of electrodes, contacts and type
of IPG not specified
Greater than 80% coverage – on table trial
and immediate implant
If failed above or intolerant, no
implantation but continue as per protocol

Both groups have UC
Comparator
Pragmatic comparator
UK RA guidelines
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Published since 1998
Not widely adopted in UK
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NRAC, Liverpool
Usual care for UK survey
Patient preference, risk and
evidence base
Therapy
Patient preference
Evidence
Risk
Mersey patient panel
CBT
+++++
+++
-
TENS
+++
++
-
SGB
++
+
+
Opioids
+++
+
+
EECP
+++
+
-
SCS
+
+++
++
PTCA
++
+++
+++
CABG
+
++++
++++++
UC
Education session with pain consultant
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Content defined
What is RA, Central sensitisation, Anxiety, collaterals
Normal IHD life expectancy, When to call ambulance dilemma
Relaxation, Stay Calm
Role of exercise training
How therapies might work
TENS
Serial SGB’s
Oral opioid or adjuvant analgesia
CBT/exercise programme - PMP
Anything else apart from EECP, CABG, PTCA or PMR
Survey of UK practice may lead to protocol revision
Outcome measures
Pilot study using a wide range
Measured by research nurse blinded to
therapy
Quality of life – Primary outcome measure
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Disease specific – Seattle Angina questionnaire
Non- disease specific – EQ5D, SF36
Functional exercise tolerance
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Baseline and 6 months
SCS on, observer blinded, BUT poor reliability
Outcome measures
Medication at baseline 3 and 6 months
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Cardiac
Pain
Diary of anginal attacks
Adverse events at 3 and 6 months
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Defined
Severity, duration, relationship to therapy
Serious adverse events
Healthcare utilisation

At 6 months from Primary & Secondary care
Timelines
Start Jan 2011
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Questionnaire and appointments (4 months)
May 2011
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18 Months Recruitment and Follow up
November 2012
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Writing report
January-June 2013 Application to NIHR
NICE Guidance
Spinal cord stimulation is recommended as a treatment
option for adults with chronic pain of neuropathic origin
who:


continue to experience chronic pain (measuring at least 50 mm on a 0–100 mm visual
analogue scale) for at least 6 months despite appropriate conventional medical
management, and
who have had a successful trial of stimulation as part of the assessment specified in
recommendation 1.3
Spinal cord stimulation is not recommended as a
treatment option for adults with chronic pain of ischaemic
origin except in the context of research as part of a
clinical trial. Such research should be designed to
generate robust evidence about the benefits of spinal
cord stimulation (including pain relief, functional
outcomes and quality of life) compared with standard
care.
NICE Guidance
Spinal cord stimulation is recommended as a treatment
option for adults with chronic pain of neuropathic origin
who:


continue to experience chronic pain (measuring at least 50 mm on a 0–100 mm visual
analogue scale) for at least 6 months despite appropriate conventional medical
management, and
who have had a successful trial of stimulation as part of the assessment specified in
recommendation 1.3
Spinal cord stimulation is recommended as a treatment
option for adults with chronic pain of ischaemic origin
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