Primary Care TodayEducational Conference and Medical ExpositionToronto, Ontario / May 8-10, 2011Adapted from a presentation by:Alan D. Bell, MD, MCFPHumber River Regional Hospital Toronto, OntarioThe Optimal Management of Diffuse Vascular Disease: Clinical Implications of the Landmark REACH RegistryProgram RationaleIn Canada there is one stroke every 10 minutes and 1 heart attack every 7 minutesSuboptimal Risk Factor Management in C/V diseaseAtherothrombosis remains the leading cause of death worldwide accounting for 47% of North American Mortality58% of Canadian high risk hypertensives NOT at goal BP in REACH were on fewer than 3 drugsNeed for Canadian primary care physicians to learn more about the management of patients with diffuse vascular disease42% of high risk atherothrombotic patients in REACH were not on evidence based risk reduction “triple therapy” Learning ObjectivesUnderstand the epidemiology and burden of atherothrombosisUnderstand the importance of registries and discuss the clinical implications of the REACH RegistryDescribe the consequences of PAD and apply Canadian guidelines for the management of PADIdentify patients with diffuse vascular disease and implement strategies for the prevention of atherothrombotic events in these patientsREACH: Reduction of Atherothrombosis for Continued Health; PAD: peripheral arterial diseaseAt the end of this session, participants should be able to: Question 1Which of the following are typical characteristics a Registry?a)Registries examine the effects of a specific interventionb)Registries usually have more exclusion criteria compared to randomized trialsc)Registries tell us about “real world” characteristics and outcomesd)Registry results are less reliable than randomized trial resultse)All of the aboveWhat is a Registry?Organized system that collects data for scientific, clinical, or policy purposesComplements RCTs by determining real-world outcomesGenerally do not:lHave restrictive inclusion or exclusion criterialSpecify what therapy the health care provider must adhere toOften used to evaluate outcomes for diverse purposes: lNatural history of a diseaselReal-world effectiveness of therapies, etc.RCTs: randomized controlled trialsExample of a Registry:Framingham Heart StudyStarted in 1948Objective: identify the common factors or characteristics that contribute to cardiovascular disease 5209 men and women, ages 30-62, from Framingham, MassachusettsExaminations every 2 yearsOver 50 years of follow-upNHLBI. Framingham Heart Study. Available at: www.nhlbi.nih.gov/about/framingham Accessed January 22, 2008.Framingham Heart Study:Atherothrombosis Reduces Life ExpectancyIn the FHS, healthy individuals aged 60 years who did not have atherothrombosis were expected to live a further 20 years to the age of 80Comparatively, patients with a history of MI lived 9.2 fewer years Those with a history of CVA lived 12 fewer years9.2Feweryears12FeweryearsLife Expectancy (Years)2020CVA: cerebrovascular accidentAdapted from Bakhai A. Pharmacoeconomics 2004;22(suppl 4):11-18.Framingham Heart Study:Cardiovascular Event Ratesin 68,000 Outpatients with AtherothrombosisRegistry ResultsREACH: PurposelDescribe the characteristics and management of patients at high risk of atherothrombosis with and without symptomatic manifestations in any vascular bedlAssess long-term risk of atherothrombotic eventslCompare outcomes lAssess the amount of “cross-risk”lAssess the impact of “diffuse vascular disease”lDefine predictors of riskAdapted from Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.Must includeSignedWrittenInformedConsentPatients aged45 yearsAt leastof four criteriaDocumented cerebrovascular diseaseIschemic stroke orTIADocumentedcoronary diseaseAngina, MI, angioplasty/stent/bypassDocumented historicalor current intermittentclaudication associatedwith ABI* 15 cigarettes/dayType I or II diabetesHypercholesterolemiaDiabetic nephropathyHypertensionABI 67,000 Patients from 5,473 Sites* in 44 Countries5,0485,6561,976Adapted from Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.BaselineFollow-up at 12 3 monthsFollow-up at 24 3 monthsFollow-up at 33 3 monthsFollow-up at 45 3 monthsREACH Registry TimelineDec 2003 to June 2004June 2007 to June 2008Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.What Does REACH Add to Our Current Understanding of Atherothrombosis?Global registryStable outpatientsLarge number of primary-care patientsIncludes multiple risk factor and manifest vascular disease patients in all 3 vascular beds4 years of follow-upBhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.Baseline DataPublished 11th Jan 2006: Bhatt DL, et al, for the REACH Registry Investigators. JAMA 2006;295(2):180-9.REACH:Significant Proportion of the Symptomatic Population has Diffuse Vascular Disease*Prevalence of disease in arterial beds (% of total)CAD: coronary artery diseasePAD: peripheral arterial diseaseCVD: cerebrovascular disease 1.61.24.78.44.716.644.6010203040506070Multiple risk factors: 18.3%CAD + CVD + PADCVD + PADCAD + PADCAD + CVDDiffuse vascular disease: 15.9%PAD AloneCVD AloneCAD AloneSingle arterial bed: 65.9%Patients (%)Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.REACH: Patient Characteristics at Baseline82.290.374.949.5Multiple RF only(n=12,389)70.272.4Hypercholesterolemia80.081.8Hypertension37.544.3Diabetes66.9% of populationSymptomatic (n=55,499)63.7Total(n=67,888)Men 69.0 (9.8)68.4 (10.1)68.5 (10.1)Mean age (SD) yr19.228.442.414.415.3Current smoker44.641.6Former smoker27.430.2Obesity (BMI 30)35.040.939.8Overweight (BMI 25 to 30)Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.Physician ProfileFollow-up available Follow-up available (%) N=63,129(%) N=63,1290.8Other (N=533)3.0Endocrinologist (N=1,987)9.4Neurologist (N=6,353)2.2Vascular surgeon (N=1,480) 1.1Angiologist (N=771)14.0Cardiologist (N=9,390)32.8Internist (N=22,244)36.7General practice (N=24,441)Physician profilePhysician profile74.79.712.33.2REACH: Risk Factors are Consistently Found Across All Disease Subpopulations*Risk factor prevalence, by subpopulation (%)80.377.038.329.913.083.358.237.423.714.38166.744.223.824.5020406080100TreatedhypertensionTreated hyper-cholesterolemiaTreated diabetesObesity(BMI 30)Current smokerPatients (%)CAD populationCVD populationPAD populationBhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.Diffuse Vascular DiseaseHow often do patients have manifest disease in more than one vascular bed?25% of the 40,258 patients with CAD also have atherothrombotic disease in other arterial territoriesCADPAD8.4%1.6%CVD44.6%(%s are of total population)Patients with CAD = 59.3% of the REACH Registry populationCAD=coronary artery diseasePAD=peripheral arterial diseaseCVD=cerebrovascular disease 4.7%Multiple risk factors only population1.Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.40% of the 18,843 patients with CVD also haveatherothrombotic disease in other arterial territories8.4%1.6%1.2%16.6%Patients with CVD = 27.8% of the REACH Registry population(%s are of total population)CADPADCVDCAD=coronary artery diseasePAD=peripheral arterial diseaseCVD=cerebrovascular disease Multiple risk factors only population1.Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.CADPADCVD60% of the 8,273 patients with PAD also haveatherothrombotic disease in other arterial territories1.2%4.7%1.6%4.7%Patients with PAD = 12.2% of the total REACH Registry population(%s are of total population)Multiple risk factors only populationCAD=coronary artery diseasePAD=peripheral arterial diseaseCVD=cerebrovascular disease 1.Bhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.1-Year OutcomesREACH: 1-year Event Curves for CV Death, MI, Stroke & Combined Endpoints 0.00.51.05.01.52.02.53.03.54.04.5Event distribution function (%)Time in months1234567891011120Non-fatal strokeCV deathNon-fatal MI infarctionCV death/MI/strokeSteg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.4.24% of these stable patients had an event within 1 yearn=64,97742% 10 year risk*Such as TIA, unstable angina, worsening of PAD; adjusted for age and genderREACH 1-year CV Event Rates: Symptomatic vs Multiple Risk Factor Only5.32.20.80.80.8Multiple RF only(n=11,766)14.412.8CV death/MI/stroke/ hospitalization for atherothrombotic events*4.74.2CV death/MI/stroke1.91.7Non-fatal stroke1.21.1Non-fatal MI1.8% of populationSymptomatic (n=53,390)1.7Total(n=64,977)CV death1.52.82.6Death all causeSteg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.1-year cardiovascular event rates as function of number of symptomatic disease locations*All p values 0.001*Pts with 3 risk factors but no symptoms are counted as 0, even in the presence of asymptomatic carotid plaque or reduced ABI*TIA, unstable angina, other ischemic arterial event including worsening of peripheral arterial diseaseOther outcomes leading to hospitalization since baseline0.51.40.50.61.1Multiple RF only(N=11,444)1.30.90.90.90.8Bleeding (leading to hospitalization and transfusion)4.13.24.23.43.1Chronic heart failure4.11.51.51.51.3Other ischemic arterial event (including worsening of PAD)1.83.21.21.51.4TIA4.9Symptomatic (N=51,685)4.2Total(N=63,129)3.4CVD(N=17,451)4.5PAD(N=7,674)6.3Unstable anginaCAD (N=37,542)Major adverse event rates at one year as a function of age: total populationRates adjusted for risk factorsGeographical Variation of 1-year Cardiovascular Event Rates6.33.01.60.80.7Japan (N=4,844)11.33.21.01.01.5Australia (N=2,822)10.04.52.30.81.5Asia (N=5,559)18.06.32.12.22.4Middle East(N=818)21.614.213.611.4CV death/MI/ CV death/MI/ stroke/ stroke/ hospitalization for hospitalization for atherothrombotic atherothrombotic eventsevents* *6.83.74.93.7CV death/MI/ strokeCV death/MI/ stroke3.5 1.52.51.1Non-fatal strokeNon-fatal stroke1.21.10.91.3Non-fatal MINon-fatal MI1.4North America (N=25,302)1.5Western Europe(N=16,487)2.2Eastern Europe(N=5,579)1.8CV deathCV deathLatin America (N=1,718)*TIA, unstable angina, other ischemic arterial event including worsening of peripheral arterial diseaseUndertreatment of Risk Factors at Study EntryBhatt DL, et al. JAMA 2006;295(2):180-9.Take-Home Messages1-year REACH results reveal:High rate of CV death, MI, and stroke (4.24%) in this “stable” outpatient population Similar risk factor profiles regardless of vascular bed involvedSignificant proportion of symptomatic patients with diffuse vascular diseaseRates increase markedly with the number of symptomatic disease locations (CV death/MI/stroke) 1.5% (risk factors only)7.1% (triple location)AtherothrombosisAtherothrombosis has Multiple ManifestationsAdapted from Drouet L. Cerebrovasc Dis 2002;13(suppl 1):16.Transient ischemic attack (TIA)Angina: Stable UnstableIschemic strokeMyocardial infarction(MI)Peripheral arterial disease (PAD): Intermittent claudication Rest pain Gangrene NecrosisAtherothrombosis: A Generalized and Progressive DiseaseAdapted from Libby P. Circulation 2001;104(3):365-372.AtherosclerosisStable angina/Intermittent claudicationUnstable angina MI Ischemic stroke/TIACritical leg ischemiaIntermittentclaudicationCV deathACSThrombosisWhat Types of Lesions Cause MI?Falk E et al. Circulation 1995;92:657-71.10080604020014%18%68%All 4studies50%-70%70%1006040200Ambrose1988Little1988Nobuyoshi1991Giroud1992Coronary Events (%)Coronary stenosis severity prior to MICoronary stenosis severity prior to MI80Pathology: Plaque Fissuring05101520253028.7Vascular disease*17.8Infectious disease12.6Cancer9.1Injuries6Pulmonary disease5.1AIDSVascular Disease* is a Leading Cause of Death WorldwideWHO. 2002. Available at: www.who.int/whr/2002/en/whr02_en.pdfMortality (%)*Ischemic heart disease, cerebrovascular disease, inflammatory heart disease and hypertensive heart diseaseWorldwide defined as Member States by World Health Organization (WHO) Region (Africa, Americas, Eastern Mediterranean, European, South-East Asia and Western Pacific)AIDS: acquired immune deficiency syndromeLeading Causes Of Death, Worldwide(% of all deaths)Epidemiology of Atherothrombotic Manifestations in CanadaAtherothrombosis: EpidemiologyPeripheral Arterial Diseaseand theCanadian PAD GuidelinesQuestion 2How common is peripheral arterial disease (PAD) in your practice?a) I hardly ever see it Its a specialist diseaseb) I have a few patients, but its much less common than coronary diseasec) Since Ive been screening for it I cant believe how common it is!d) I dont know, because I have no way to test for ite) I dont look for it because none of my patients ever died of a “leg attack”lOften asymptomatic, under-diagnosed, under-recognized, and under-treated l16% of North America and Europe has PAD, corresponding to 27 million peoplelOf these, 16.5 million are asymptomaticGupta A. In: Abramson BL, et al. Can J Cardiol 2005;21(12):997-1006.PAD: EpidemiologyCCS Guidelines: Diagnosis of PAD Roussin A, et al. Can J Cardiol. 2005;21(12):9971006. RecommendationGradeTaking a directed history for symptoms of PAD. A validated questionnaire, such as the Edinburgh Questionnaire, can help diagnose arterial claudication in patients suspected of suffering from PAD.1APerforming a directed examination focusing on physical findings that have been proven useful to detect PAD defined as an ABI1.300.91-1.300.41-0.900.00-0.40NoncompressibleNormalMild-to-moderate peripheral arterial diseaseSevere peripheral arterial diseaseQuestion 3Which of the following are TRUE regarding symptomatic PAD?a) 30% will suffer a fatal vascular event within 5 yearsb) Ankle / Brachial Index (ABI) is sensitive and specific enough to make the diagnosis of PADc) Severity of disease and mortality may be predicted by ABId) Exercise programs can improve claudication symptomse) All of the aboveLocal consequences in the leg include:Intermittent claudicationTissue loss including sepsis and major amputationsPAD is a marker of disease in other vascular bedsFatal and non-fatal cerebral and coronary vascular eventsConsequences of PAD may be Local and SystemicREACH: Reduction of Atherothrombosis for Continued HealthPatients with Previous Atherothrombotic Events are at Increased Risk of Further Events Increased risk versus general populationMIStrokeIschemic stroke2-3x(includes angina and sudden death*)19x2MI5-7x(includes death)33-4x(includes TIA)1PAD4x(includes only fatal MIand other CHD death)42-3x(includes TIA)2* Sudden death defined as death documented within 1 hour and attributed to coronary heart disease (CHD). Includes only fatal MI and other coronary heart disease (CHD) death; does not include non-fatal MI.1. Kannel WB. J Cardiovasc Risk1994;1(4):333339.; 2. Wilterdink JL, et al. Arch Neurol 1992;49(8):857863. 3. Adult Treatment Panel II. Circulation 1994;89(3):13331363. 4. Criqui MH, et al. N Engl J Med 1992;326(6):381386.Consequences of PAD Population 55 years of ageSurgery or tissue loss25%Adapted from Weitz JI, et al. Circulation 1996;94(11):3026-3049.Stable claudication50%5-year peripheral vascular outcomesWorsening claudication16%5-year natural history of intermittent claudicationMajor amputation 1.1 0.9 1.1 0.7 0.9 0.5 0.7 0.5Proportion alivelPatients with symptomatic PAD have a5-year mortality rate of 28%-compared with 15% for breast cancer -and 18% for Hodgkins disease1lPatients with PAD are 6 X more likely to die within 10 years than those without PAD1PAD: A Major Health Burden1. Criqui MH, et al. N Eng J Med 1992;326(6):381-386. 2. Gupta A. In: Abramson BL, et al. Can J Cardiol 2005;21(12):997-1006.lPatients with PAD are 6 X more likely to die within 10 years than those without PAD1lPatients with PAD often have decreased quality of life because of pain during walking and limitations in mobility21. Criqui MH, et al. N Eng J Med 1992;326(6):381-386. 2. Belch JJ, et al. Arch Int Med 2003;163(8):884-892.PAD: A Major Health BurdenQuestion 4What are the most powerful risk factor(s) for development of PAD?a) Risk factors for PAD are similar to those in all vascular bedsb) Smoking is more predictive for PAD than the other traditional risk factorsc) Diabetes is more predictive for PAD than the other traditional risk factorsd) All of the aboveRisk Factors for PADTeo KK. In: Abramson BL, et al. Can J Cardiol 2005;21(12):997-1006.Risk factors for PAD are similar to those for atherosclerosis in other beds and include:Non-ModifiableModifiableAgeFamily historyMale sexCigarette smokingDiabetesElevated lipid levelsHypertensionObesitySedentary lifestyleREACH: Risk Factors are Consistently Found Across All Disease Subpopulations*80.377.038.329.913.083.358.237.423.714.38166.744.223.824.5020406080100TreatedhypertensionTreated hyper-cholesterolemiaTreated diabetesObesity(BMI 30)Current smokerPatients (%)CAD populationCVD populationPAD populationBhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.Take-Home MessageslAtherothrombosis is a generalized and progressive diseaselAcute vascular events are the result of sudden plaque rupturelPAD is associated with significant morbidity and mortality due to local and systemic complicationslCurrently, PAD is under-diagnosed and under-treatedlCigarette smoking and diabetes are the strongest risk factors for PADHyperlinks to Patient VignettesVignette 3: John63-year-old government employee with recently diagnosed PAD Vignette 1: Louise56-year-old female who experienced a mild ischemic stroke 6 months ago and has since made a full recoveryVignette 2: Todd58-year-old retired executive with PAD who experienced a MI 6 months ago ( i.e., diffuse vascular disease)Patient Vignette: LouiselLouise is a 56-year-old office managerl6 months ago she experienced a mild ischemic strokelShe has since made a full recovery with no residual signs/symptomslHer current medications include anti-platelet therapy, an ACE inhibitor and a statinlLouise comes to your office today for a routine visit and tells you that she would like to return to workQuestion 5Which of the following in NOT appropriate Anti-platelet therapy for Louise?a)ER Dipyrdamole 200 mg plus ASA 25 mg BIDb)ECASA 81 mg plus clopidogrel 75 mg ODc)ECASA 81 - 325 mg OD aloned)Clopidogrel 75 mg OD alonee)None of the above, all are reasonableMATCH: ResultsCumulative Event Rate(Ischemic Stroke, MI, Vascular Death, Rehospitalization due to Ischemic Event)Months of follow-up6.4% RRR1.03% ARR P=0.24406121801361218Cumulative event rate (%)PlaceboASAOn-Treatment Analysis: 9.6% RRR, 1.6% ARR, p=0.10* All patients received clopidogrel background therapyDiener HC, et al. Lancet. 2004; 364:331-337.ESPS 2:Risk Reduction for Stroke or Death Stroke relative risk reduction (%)P0.001P0.05P0.05P=0.006ER DP = extended release dipyridamolen = 6602 within 3 months of stroke or TIA 2 years of follow-upDiener HC, et al. J Neurol Sci. 1996;143:1-13. Antithrombotic Trialists CollaborationASA dose500 1500 mg daily160 325 mg daily75 150 mg daily 75 mg dailyAny ASA dose0.00.51.01.5ASA betterControl better% odds reduction*Antithrombotic Trialists Collaboration. BMJ. 2002;324:71-86.23% + 2(P0.0001)*Vascular events = MI, stroke or vascular death75-150 mg ASA daily is at least as effective as higher daily ASA doses which carry higher risk of GI bleeding2010010203040Outcome = IS, MI, vascular deathClopidogrel better8.7%14.9%CAPRIE:Clopidogrel vs ASA in Patients with Previous Acute Events Patients with previous acute events Entire CAPRIE sampleOutcome = IS, MI, rehospitalization for angina/ claudication/peripheral ischemia/TIA/MI Patients with previous acute events Entire CAPRIE sample12.0%9.0%Ringleb PA, et al. Stroke. 2004;35:528-532.ASA betterCAPRIE: Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events2006 AHA/ASA Guidelines:Prevention of Stroke in Patients with Ischemic Stroke or TIASacco RL, et al. Stroke. 2006;37:577617. Antithrombotic Therapy for Non-Cardioembolic Stroke or TIARecommendationClass, level of evidenceAntiplatelet agents rather than oral anticoagulationI, AASA (50 to 325 mg/d)ASA + extended-release dipyridamoleClopidogrelAll acceptable options for initial therapyIIa, AASA + extended-release dipyridamoleClopidogrelBoth safe compared with ASA monotherapyIIa, AQuestion 6With regard to her future vascular risk: a)Her greatest risk of death in the next 12 months is recurrent strokeb) There is a high probability that she has atherothrombotic disease in the coronary and peripheral circulationc) Long term she is more likely to die from recurrent stroke than cardiac diseased) All of the abovee) None of the above40% of CVD patients also have symptomatic disease in the coronary or peripheral circulationBhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.REACH:Overlapping Manifestations of DiseaseCause of deathFirst strokeRecurrent strokeCardiovascular diseaseNonvascular diseaseUnknownHankey GJ, et al. Stroke 2000;31(9):2080-2086.Long-Term Cause of Stroke Mortality Risk at 5 YearsTime since first-ever stroke0102030405060708090100 30d30d6m6m1yr1-3yr3-5yr%Question 7 - Suppose Louise also experienced an Acute Coronary Syndrome within the past year. How would this impact her risk for subsequent atherothrombotic events?a)She remains at equally high risk regardless of the presence of diffuse vascular diseaseb) Her risk reduction strategies should remain unchangedc) She would benefit from dual anti-platelet therapy with ASA 81 mg plus clopidogrel 75 mgd) More aggressive lipid and blood pressure targets should be appliede) All of the aboveCURE Primary Endpoint: MI/Stroke/CV Death (n=12,562*)The primary outcome occurred in 9.3% of patients in the clopidogrel + ASA group and 11.4% in the placebo + ASA groupMonths of Follow-upClopidogrel + ASA369Placebo + ASA012Cumulative Hazard Rate0.000.020.040.060.080.100.120.1420%20%Relative Relative Risk ReductionRisk Reduction p=0.00009 *Study subjects had ACS (Acute Coronary Syndrome - UA/nonQ-wave MI). Other standard therapies were used as appropriate.CURE Trial Investigators. N Engl J Med 2001;345(7):494-502.CURE: Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events 200 mg0.01.02.03.04.05.06.0Bleeding rate (%)ASA dose 75-325 mg*In addition to standard therapy (including ASA).2.02.62.33.54.04.9Placebo*Clopidogrel*CURE: Major Bleeding by ASA DoseCURE Trial Investigators. N Engl J Med 2001;345(7):494-502.CV death/MI/stroke/hospitalization (%)Number of disease locationsP0.001*Multiple risk factor groupREACH: 1-year CV Event Rates as a Function of the Number of Symptomatic Disease LocationsSteg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.Risk sharply increases with diffuse vascular diseaseHOPE: Risk Reduction with ACE InhibitionMinimal changes in BP; non-hypertensive sub-group noted similar benefitYusuf S, et al. N Engl J Med 2000;342(3):145-153.CVD deathStrokeNon-fatal MITotal morality26%32%20%16%p0.001p0.001p0.001p=0.005HOPE: Heart Outcomes Prevention Evaluation0.050.100.150.201234Follow-up time (years)Proportion with event28% risk reduction95% CI 1738%P0.0001ARR (%) = 4.0placeboperindopril-based treatment6,105 subjects with cerebrovascular event within past 5 yearsNo BP entry requirementPROGRESS: Stroke ReductionPROGRESS Collaborative Group. Lancet 2001;358(9287):1033-1041. PROGRESS: Perindopril Protection Against Recurrent Stroke StudySPARCL: Primary End-point: Fatal or Non-fatal StrokeThe SPARCL Investigators. N Eng J Med 2006;355(6):549-559.Time since randomization (years)*AdjustedFatal/ nonfatal stroke(%)00123456161284PlaceboAtorvastatin16% RRR*HR 0.84 (0.710.99)P=0.03SPARCL: Stroke Prevention by Aggressive Reduction in Cholesterol LevelsCAPRIE:Clopidogrel vs. ASA in Multi-bed Disease1550Annual event rate (%)ClopidogrelASAEvents = ischemic stroke, MI or vascular deathCAPRIE Steering Committee. Lancet 1996;348(9038):1329-1339.108.35%10.74%164 events196 events22.7%Relative RiskReductionCAPRIE: Clopidogrel vs Aspirin in Patients at Risk of Ischemic Eventsn=3284n=12,153n=15,603CHARISMA: Treatment Effect by Inclusion CriteriaCombined endpoint: MI, stroke, CV death*Multiple atherothrombotic risk factorsDocumented CAD, CVD and/or PAD0.51.01.5PlacebobetterClopidogrelbetterAsymptomatic*SymptomaticAll patientsHazard ratioRR (95% CI)1.20 (0.911.59)0.88 (0.770.998)0.93 (0.831.05)Bhatt DL, et al. N Engl J Med 2006;354(16):1706-1717.P=0.20P=0.046P=0.22CHARISMA: Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and AvoidanceTake-Home MessageslApproximately 40% of patients with CVD in the REACH Registry had diffuse vascular diseaselCompared with a history of disease in a single vascular bed, diffuse vascular disease doubles the risk of a major CV event or hospitalization within 1 yearlAggressive risk reduction strategies including ACE inhibition, statins and antiplatelet therapy should be considered for patients with diffuse vascular diseaselCHARISMA showed that patients with a prior atherothrombotic event benefit from long-term dual antiplatelet therapy (median follow-up 27 months)Patient Vignette: JohnlJohn is a 63-year-old government employeelLast month, he came to your office complaining of left calf pain when walking a couple of blocks; the pain went away after a few minuteslBased on your history and clinical examination at this time, you suspected John had symptomatic PAD and sent him for an ABIlJohns ABI was 0.90 (R) 0.77 (L), which confirmed your diagnosisABI: ankle brachial indexQuestion 8Unless contraindicated, which of the following are necessary risk reduction strategies for John?a) Statin therapy to reduce LDL to 55 years of ageSurgery or tissue loss25%Adapted from Weitz JI, et al. Circulation 1996;94(11):3026-3049.Stable claudication50%5-year peripheral vascular outcomesWorsening claudication16%5-year natural history of intermittent claudicationMajor amputation4%Intermittent claudication 5%Other cardiovascular outcomes5-year non-fatal atherothrombotic events (MI, stroke, etc.) 20%5-year mortality30% REACH:Vascular Interventions at 1 Year0.31.60.30.30.4Amputation0.45.00.91.01.2PAD angioplasty/ stenting0.20.30.20.50.9Multiple RF only(n=11,966)3.70.50.60.8Peripheral bypass graft1.00.70.40.5Carotid surgery0.60.40.30.3Carotid angioplasty/ stenting1.00.71.41.1CABG2.9Total symptomatic (n=53,390)1.5CVD(n=18,013)2.4PAD(n=8,581)3.8Coronary angioplasty/ stentingCAD (n=38,602)CABG: coronary artery bypass graft; adjusted for age and genderSteg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.Local SystemicREACH:Vascular Interventions at 1 YearRevascularization at 1 year (%)Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.(n=18,013)(n=38,602)(n=8,581)Question 9Which of the following anti-platelet strategies are NOT appropriate for John?a) ASA 81 mg ODb) Clopidogrel 75 mg ODc) ASA 81 mg OD plus Clopidogrel 75 mg ODd) ER Dipyrdamole 200 mg plus ASA 25 mg BIDe) None of the above (all are appropriate)CCS Guidelines:Antithrombotic TherapiesAGENTRECOMMENDATIONGRADEASA or ClopidogrelLifelong antiplatelet therapy with ASA (75 to 325 mg/day) or clopidogrel (75 mg/day) in patients with or without clinically manifest coronary or cerebrovascular disease1ATiclopidineASA or clopidogrel recommended over ticlopidine1BCilostazol*Recommendation for patients with disabling intermittent claudication who do not respond to conservative measures (risk factor modification and exercise therapy) and who are not candidates for surgical or catheter-based intervention1BPentoxifyllinePentoxifylline is not recommended2BVitamin K AntagonistsAnticoagulant therapy is not recommended2B*Not available in CanadaAnand SS, Turpie AGG. In: Abramson BL, et al. Can J Cardiol 2005;21(12):997-1006.Question 10What percentage of symptomatic Canadian REACH Registry patients are currently on “Triple Therapy” (ACE or ARB + Statin + Anti-platelet agent)a) 95 %b) 80 %c) 75 %d) 70 %e) 60 %REACH: Proven Therapies are Consistently Underused in All Patient Types*(n=12,389) (n=8,273) (n=18,843)(n=40,258)Patients receiving proven therapy (%)ARB: angiotensin II receptor blocker*Data shown may differ slightly from published abstracts owing to a subsequent database lockBhatt DL et al, on behalf of the REACH Registry Investigators. JAMA 2006;295(2):180-189.CRUSADE: Link Between Guideline Adherence and In-hospital MortalityAdjusted figuresPeterson ED, et al. ACC Annual Scientific Session. 2004. Available at: http:/www.crusadeqi.comImproved Guideline AdherenceCRUSADE : Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA GuidelinesApproximately 1 in 5 patients with PAD will experience CV death, MI, stroke, or hospitalization within 1 yearBreakdown of event ratesPADCADCVD21.1%1 in 515.2%1 in 614.5% 1 in 7Steg PG et al, on behalf of the REACH Registry Investigators. JAMA 2007;297(11):1197-1206.Take-Home MessagesTake-Home Messages (continued) 60% of patients with PAD have diffuse vascular disease 15% of patients with PAD will require a vascular intervention at 1 yearLifelong antiplatelet therapy with ASA or clopidogrel is recommended for patients with PADAdherence to guideline recommendations may lead to reduced mortality in PAD