Asasantin Retard in Stroke Prevention : a Clinical and Business Perspective

1
Asasantin Retard in Stroke Prevention a
Clinical and Business Perspective

• by Dr U Ahmed
• Consultant Physician, Management Consultant,
  Medico-Legal Bioethics Consultant

2
Introduction - 1

• Clinical Perspective
• Epidemiology of Stroke and TIAs
• Primary Prevention of Stroke
• Secondary Prevention of Stroke
• Role of Antiplatelet Agents
• The Future

3
Introduction - 2

• Business Perspective
• Strategic Perspective
• strategic issues / choices / levels / fit
• strategy and competitive advantage
• Marketing perspective
• marketing theory / transactions vs.
• 
  relationship
• marketing analysis / mix / plan / strategy

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Epidemiology of Stroke TIA

• Stroke
• incidence 2.4/1000-OCSP
• 2400 strokes per year/1m
• 1800 new 600 recurrent
• of this, 700 die at 1yr 1700 for sec. Prev.
• added each year to 12,000/1m with previous TIA,
  Stroke or both i.e. prevalent

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Epidemiology - 2

• Stroke
• therefore, new Stroke survivors each year is 1700
  i.e. 1100 independent 600 depend
• added to 12,000/1m people with previous stroke
  (8000), TIA (3000) or both (1000)
• of the 12,000-800 (7) will have a stroke per
  year i.e. 600 recurrent strokes 200 new

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Epidemiology - 3

• Stroke
• these 800 strokes i.e. 33 of the 2,400/1m/yr are
  those potentially avoidable by secondary
  prevention strategies targeted at the 12,000
  prev. TIA/Stroke/both/1m/yr
• TIA
• 0.5/1000 inc.- 500/1m/yr new TIAs

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Prevention of Stroke

• Risk Factor Modification
• Management of TIAs
• Antiplatelet Therapy
• Anticoagulant Therapy
• Other Medical Therapy -PROGRESS
• Carotid Endarterectomy
• NNTs

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Current Management of TIAs an overview

• Risk factors
• non-modifiable
• age
• sex
• family history
• ethnicity
• modifiable
• hypertension, hypercholesterolaemia,
• diabetes, smoking, alcohol, physical inactivity

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Other risk factors

• oestrogens
• Homocysteinuria
• lipoprotein fractions
• hypercoagulable states antiphospholipid
• abs, protein S, C, factor V Leiden,
• antithrombin III defs

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Hypertension

• SHEP
• SYST EUR 42 stroke risk reduction in sys hyp
• HOT
• BHS Guidelines
• PROGRESS
• PATS CAPPP, SYS REVIEW - 1997 2001, HOPE

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Diabetes mellitus

• UKPDS - 44 stroke risk reduction with BP Rx
• High stroke risk in 2HBS gt 97 centile
• Low BM reduce microvascular disease NOT
  macrovascular

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Life style factors

• Smoking
• Alcohol
• Physical inactivity
• Poor diet
• Obesity

13
Hyperlipidaemia

• No RCTs for lipid in TIA or Stroke yet
• On-going Trials SPARCL, PROSPER, etc.
• Meta-analysis of RCTs on Statins in IHD- e.g. 4S,
  WOSCOP etc.
• - 29 stroke risk reduction
• - 22 reduction in overall mortality

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Hyperlipidaemia, cont.

• Secondary prevention trials 32 stroke risk
  reduction
• Primary prevention trials 20 stroke risk
  reduction
• ? Current consensus on Statins in TIA or Stroke -
  PHS, SPARCL, PROSPER

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Oestrogens

• Pill
• HRT in TIA / Stroke
• Women Oestrogen Stroke Trial, Oestrogen
  Progestegin Interventions Trial
• Other
• Homocysteine Trials VISP, VITATOPS etc.
  (folate, B6, B12)

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MEDICAL THERAPYAntiplatelet agents

• Aspirin
• cyclo-oxygenase inhibition side effects -recent
  Meta-analysis
• ? Optimal dose 25mg to 1500mg per day !
• UK TIA Aspirin Study 300mg v. 1200mg no
  difference

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Antiplatelet agents, cont.

• Dutch TIA Study- Aspirin 30mg vs. 283mg no
  difference in stroke risk reduction
• ACE Study lower better overall vascular risk
  reduction 6.2 vs. 8.4 for Aspirin 130mg vs.
  326mg respectively no difference in Stroke Risk
  reduction
• NASCET Higher Dose Better ?Relevance to TIA
  but not Endarterectomy
• FDA/Consensus Aspirin 50 to 325mg/day
• High Risk patients benefit from Aspirin (HOT,
  TPT, PPP) not Low Risk (BDS, PHS)

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Antiplatelet agents, cont.

• Ticlopidine
• Inhibits ADP-PLT Aggregation
• Side effects diarrhoea, TTP, Neutropaenia
• CATS 23.3 Stroke Risk Reduction ( other
  Vascular events)
• TASS ASP 650mg bd vs. TCL 250mg bd TCL Better
  reduction in Stroke All-Cause Mortality by
  12 vs. 7 at 3 years and Stroke Risk by 21
• Use USA - Asp intolerance Asp failures
  cardiology - UK

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Antiplatelet agents, cont.

• Clopidogrel Use in Aspirin-intolerance
  failures
• Ticlopidine Structure Inhibits ADP-PLT
  Aggregation
• S.e diarrhoea, rash, Git bleed
• CAPRIE CAPRA CLOP ASP Trials
• Clop 75mg vs. Asp 325mg in Stroke, MI, PVD but
  not TIAs 19,000 pts
• Clop reduced COMPOSITE outcome risk by
• 8.7 in favour
• NO Significant difference in Stroke Subgroup

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Antiplatelet agents, cont.

• Dipyridamole (Aspirin)
• Phosphodiesterase inhibitor
• Trials 5
• French Toulouse Study no difference 440 TIA
  PTs Asp vs. Dipy vs. Asp Dipy
• AICLA Study - 604 TIA/Stroke PTs given Asp vs.
  Asp Dipy vs. Placebo 42 Stroke Risk
  Reduction with Asp no Added Benefit from Dipy

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Antiplatelet agents, cont.

• ACCS 890 Stroke/TIAs- given Asp vs. Asp Dipy
  vs Placebo Reduced Stroke Risk no difference
  between Asp and Combination
• ESPS -1- Placebo vs. Asp Dipy 33 Reduction
  in Risk of Stroke Death 38 Stroke Risk
  Reduction 2,500 Stroke/TIA pts

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Antiplatelet agents, cont.

• ESPS-2 Asp Dipy MR vs. Asp vs. Dipy MR vs.
  Placebo
• Asp 18 Stroke Risk Reduction
• Dipy MR 16 Stroke Risk Reduction
• Asp Dipy MR 37 Stroke Risk Reduction
• 23.1 Better Than Aspirin Alone
• 24 Better Than Dipyr MR Alone
• S.e. Headaches Use-Asp intolerance failures
• ? Triple AntiPlatelet Therapy

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COST per YEAR

• Aspirin 2
• Asp Dipy MR 119
• Clopidogrel 460
• Ticlopidine 1,217
• Efficacy - slide

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• Anticoagulants - ?optimal INR ?wafarin in Stroke
• AF Warfarin Rx of Choice Other Indications
  -Cardio-embolic Atherothrombotic - no RCTs yet
  - Warfarin Aspirin Recurrent Stroke Study,
  Euro-Austr Stroke Prev Trial
• SPAF I, II, III and EAF Trial - Future ?Thrombin
  Inh e.g. SPORTIF III
• Increased Stroke Risk in AF
• hypertension, pmh TIA/Stroke
• poor LV function, systemic embolism
• RHD, age gt75 years
• prosthetic valves

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SURGICAL RxCarotid Endarterectomy

• Asymptomatic
• ACAS Trial gt60 stenosis 1600 Pts ARR 4.9
  (11 vs. 6.1) 5 yr FU
• VAStudy gt50stenosis 444 Pts ARR 12.6 (20.6
  vs. 8) 4 yr FU

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SURGICAL RxCarotid Endarterectomy cont.

• Symptomatic - NASCET - 70 - 99 Sten 2226 Pts
  ARR17 (26 vs. 9) 2yr FU
• ECST-70-99 stenosis 3024Pts ARR11.6 (26.5
  vs.14.9) 3yr FU NNT8
• NASCET - 70 - 99stenosis 2226Pts ARR17(26
  vs. 9) 2yr FU Benefit in 50-69
• Risk-factor modelling Role of IAD

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• Angioplasty
• CAVATAS
• Posterior Circulation TIAs - angioplasty
  -Vertebral Artery
• surgery
• TIA CLINIC

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NNTs - 1

• Acute Stroke Treatment
• Stroke Unit - 18
• Aspirin - 83 (Rx of Acute Stroke)
• Thrombolysis - 16

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NNTs - 2

• Stroke Prevention
• Anti-hypertensive Rx - 45
• Smoking Cessation - 43
• Statins - 59
• Aspirin - 100
• Clopidogrel - 62
• Aspirin Dipyridamole MR - 53

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NNTs -3

• Anticoagulants - 12
• Carotid Endarterectomy - 26 (symptomatic)
• See ACETATES - for DETAILS !

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Business Perspective

• Strategy Perspective
• Strategic issues/- Strategic choices
• - determine scope of activities
• - evaluate success of activities
• - acquire allocate resources capability
• - create effective match challenges in env
• - manage networks c b/w stakeholders

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Business Perspective - 2

• Strategy perspective
• Levels of strategy- corporate/bus/intern units
• Strategic success / fit - corporate success based
  on effective match b/w external relationships of
  a firm and its own distinctive capabilities
  (Kay,1993)

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Business Perspective - 3

• Strategy Perspective
• Competitive advantage - your most dangerous
  competitors are those that are most like you.
  The difference b/w you and your competitors is
  the basis of your advantage (Henderson,1989)

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Business Perspective - 4

• Strategy Perspective
• Strategic stretch
• - creating a chasm b/w an organisations
• resources / capabilities /
  ambition
• - bridging the chasm through leveraging
• resources capabilities
• (Hamel
  Prahalad, 1993)

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Business Perspective - 5

• Strategy Perspective
• Resources - input into production process few
  are productive on their own. Productive activity
  requires the co-operation
• co-ordination of a team of resources
• Capability - capacity of a team of resources to
  perform activities is a source of competitive
  advantage (Grant,1991)

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Business Perspective - 6

• Leveraging Resources
• concentrate resources on strategic goals
• accumulate resources efficiently
• complement types of resources - add value
• conserve resources - avoid waste !
• recover resources from market - in
• 
  minimum time !

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Business Perspective - 7

• Competitive Advantage - potential / superior rate
  of profit
• Sources of Competitive Advantage
• - strategic assets e.g. knowledge / exclusivity
• - distinctive capabilities e.g. innovation
• - differentiation image, support, price,
  design
• - cost leadership economies of scale,
  learning,
• 
  efficiency

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Business Perspective - 8

• Exploiting Competitive Advantage
• Sustainability durable, transparent,
  transferable, replicable
• Appropriateness
• Responding to Opportunity for Comp Adv
• - Key resource Information
• - Key Capability Flexibility of Response

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Marketing Perspective

• Marketing
• Marketing Theory
• Transaction / Relationship Marketing
• Marketing Analysis
• Marketing Mix
• Marketing Plan
• Marketing Strategy

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Marketing

• Management process responsible for matching
  resources with opportunities at a profit, by
  identifying, anticipating, influencing,
  satisfying customer demand (UKCIM)
• Social managerial process by which individuals
  groups obtain what they need through creating
  exchanging value(Kotl)

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Marketing Theory

• Perfect Markets vs. Imperfect Markets
• many buyerssellers
• perfect knowledge
• homogenous products - customers indifferent b/w
  sellers
• no barriers to movement of goods or factors of
  production

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Marketing Types

• Transaction vs. Relationship Marketing
• relational
• mutual benefit
• long-term
• strategic
• cost effective
• reputation

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Marketing Analysis

• Systematic understanding of the existing
  potential markets for products services,
  providing this info to MX and making
  recommendations on how the customers
  requirements might best be served /met.

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Marketing Analysis

• What do you analyse?
• Buying decisions of your product / service
• Who do you analyse?
• Customers decisions, needs, aspirations,
• expectations
• Competitors performance, goals,
• 
  capability
• Yourself offering, performance, capability
• How do you analyse? Research Audit

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Market Research/Audit

• Systematic problem-analysis, model-building
  fact-finding for the purpose of improved
  decision-making control in the marketing of
  goods services. (Birn,1992)
• Analyses of internal reporting systems relating
  to all aspects of sales / purchases,
  distribution invoicing can highlight problems
  opportunities

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Market Research

• Why ?
• To reduce uncertainty
• To monitor performance
• To contribute to strategic processes - by helping
  organisations understand the relationship to
  their environment
• How? Quantitative
• e.g. exp vs. Qual
  - surveys

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Competitor Analysis

• Info on - goals, strategies, beliefs,
  capabilities, nature / changes, strengths,
  weaknesses, marketing operations
• Methods - value chain analysis, SWOT,
  organisational culture structure, managerial
  features, strategic factors

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Marketing Mix/Plan

• 7 Ps Product, Price, Promotion, Place, People,
  Process, Physical Evidence
• Marketing Plan the process by which resources
  are allocated to meet specific marketing
  objectives - knit together strategic day-to-day
  elements of marketing

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Marketing Plan

• McDonald 9-point Plan
• mission, performance survey, financial
  prospecting, market overview, SWOT analyses,
  portfolio summary ( segment planning),
  assumptions underpinning plan, setting objectives
  strategies, financial budgets

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Marketing Strategy

• Monitor industry, competition,
• 
  environment
• Evaluate market opportunities threats
• Identify competitive options
• 
  strategies
• Development detailed marketing plan /
• implementation
  review
• Methods SWOT, STEEP, Ansoff, Porter-
• 
  cdf