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Asasantin Retard in Stroke Prevention : a Clinical and Business Perspective. by Dr U Ahmed Consultant Physician, Management Consultant, Medico-Legal & Bioethics Consultant. Introduction - 1. Clinical Perspective Epidemiology of Stroke and TIAs Primary Prevention of Stroke
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Asasantin Retard in Stroke Prevention : a Clinical and Business Perspective by Dr U Ahmed Consultant Physician, Management Consultant, Medico-Legal & Bioethics Consultant
Introduction - 1 Clinical Perspective • Epidemiology of Stroke and TIAs • Primary Prevention of Stroke • Secondary Prevention of Stroke • Role of Antiplatelet Agents • The Future
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
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
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
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
Prevention of Stroke • Risk Factor Modification • Management of TIAs • Antiplatelet Therapy • Anticoagulant Therapy • Other Medical Therapy -PROGRESS • Carotid Endarterectomy • NNTs
Current Management of TIAs an overview Risk factors • non-modifiable • age • sex • family history • ethnicity • modifiable • hypertension, hypercholesterolaemia, • diabetes, smoking, alcohol, physical inactivity
Other risk factors • oestrogens • Homocysteinuria • lipoprotein fractions • hypercoagulable states : antiphospholipid abs, protein S, C, factor V Leiden, antithrombin III defs
Hypertension • SHEP • SYST – EUR – 42% stroke risk reduction in sys hyp • HOT • BHS Guidelines • PROGRESS • PATS; CAPPP, SYS REVIEW - 1997 & 2001, HOPE
Diabetes mellitus • UKPDS - 44% stroke risk reduction with BP Rx • High stroke risk in 2HBS > 97 centile • Low BM reduce microvascular disease NOT macrovascular
Life style factors • Smoking • Alcohol • Physical inactivity • Poor diet • Obesity
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
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
Oestrogens • Pill • HRT in TIA / Stroke • Women Oestrogen Stroke Trial, Oestrogen & Progestegin Interventions Trial Other : • Homocysteine Trials – VISP, VITATOPS etc. (folate, B6, B12)
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
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)
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
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
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
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
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
COST per YEAR Aspirin £ 2 Asp + Dipy MR £ 119 Clopidogrel £ 460 Ticlopidine £ 1,217 Efficacy - slide
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 >75 years • prosthetic valves
SURGICAL RxCarotid Endarterectomy Asymptomatic • ACAS Trial : >60% stenosis; 1600 Pts; ARR 4.9% (11% vs. 6.1%); 5 yr FU • VAStudy : >50%stenosis; 444 Pts; ARR 12.6% (20.6% vs. 8%); 4 yr FU
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 - 99%stenosis; 2226Pts; ARR17%(26% vs. 9%); 2yr FU; Benefit in 50-69% • Risk-factor modelling; Role of IAD
Angioplasty • CAVATAS • Posterior Circulation TIAs - angioplasty -Vertebral Artery • surgery • TIA CLINIC
NNTs - 1 Acute Stroke Treatment • Stroke Unit - 18 • Aspirin - 83 (Rx of Acute Stroke) • Thrombolysis - 16
NNTs - 2 Stroke Prevention • Anti-hypertensive Rx - 45 • Smoking Cessation - 43 • Statins - 59 • Aspirin - 100 • Clopidogrel - 62 • Aspirin + Dipyridamole MR - 53
NNTs -3 • Anticoagulants - 12 • Carotid Endarterectomy - 26 (symptomatic) See ACETATES - for DETAILS !
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
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)
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)
Business Perspective - 4 Strategy Perspective • Strategic stretch - creating a chasm b/w an organisation’s resources / capabilities / ambition - bridging the chasm through leveraging resources & capabilities (Hamel & Prahalad, 1993)
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)
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 !
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
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
Marketing Perspective • Marketing • Marketing Theory • Transaction / Relationship Marketing • Marketing Analysis • Marketing Mix • Marketing Plan • Marketing Strategy
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)
Marketing Theory Perfect Markets vs. Imperfect Markets • many buyers&sellers • perfect knowledge • homogenous products - customers indifferent b/w sellers • no barriers to movement of goods or factors of production
Marketing Types Transaction vs. Relationship Marketing • relational • mutual benefit • long-term • strategic • cost effective • reputation
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.
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
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
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
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
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
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
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