Critical Appraisal Did the study address a clearly focused question? Did the study address a clearly focused question? Was the assignment of patients.

Critical AppraisalCritical Appraisal Did the study address a clearly focused question?Did the study address a clearly focused question? Was the assignment of patients randomised?Was the assignment of patients randomised? Were all patients who entered properly accounted for?Were all patients who entered properly accounted for? Was the follow up complete?Was the follow up complete? Were the groups similar at the start of the trial?Were the groups similar at the start of the trial? Were all people involved blind to the treatment?Were all people involved blind to the treatment? Were the groups treated equally aside from the Were the groups treated equally aside from the experimental interventions?experimental interventions? Can the results be applied to my patient care?Can the results be applied to my patient care? Were all clinically important outcomes considered?Were all clinically important outcomes considered? What are the likely benefits are they worth the potential What are the likely benefits are they worth the potential

harm and costs?harm and costs?

BackgroundBackground

In acute coronary syndromes Dual platelet In acute coronary syndromes Dual platelet therapy is the current recommendationtherapy is the current recommendation

Current drugs include Asprin and Current drugs include Asprin and ClopidogrelClopidogrel

Clopidogrel Clopidogrel Needs to be MetabolizedNeeds to be Metabolized Rate and efficacy of this process is slowRate and efficacy of this process is slow

PrasogrelPrasogrel Higher risk of bleedingHigher risk of bleeding

BackgroundBackgroundTicagrelorTicagrelor

MethodsMethods

Double blinded randomized controlled Double blinded randomized controlled multi centre trialmulti centre trial

Drug superiority trialDrug superiority trialEnd pointsEnd points

Vascular eventsVascular eventsDeathDeath

Aztra Zeneca is the sponsorAztra Zeneca is the sponsor

MethodsMethods

Inclusion criteria Inclusion criteria Acute coronary syndrome within 24 hrs of onset of Acute coronary syndrome within 24 hrs of onset of

symptomssymptoms

Exclusion criteriaExclusion criteria Contra indication to ClopidogrelContra indication to Clopidogrel Fibrinolytic therapy within 24 hrs of randomizationFibrinolytic therapy within 24 hrs of randomization A need for oral anticoagulation therapyA need for oral anticoagulation therapy An increased risk of brady cardiaAn increased risk of brady cardia P450-3a inhibitor or inducerP450-3a inhibitor or inducer

MethodsMethods

MethodsMethods

TreatmentTreatment Randomized to get either ticagrelor or clopidogrelRandomized to get either ticagrelor or clopidogrel Double blind therapyDouble blind therapy TicagrelorTicagrelor

180mg loading dose180mg loading dose 90mg twice dly90mg twice dly

ClopidogrelClopidogrel 300mg loading dose300mg loading dose 75mg dly 75mg dly

If undergoing PCIIf undergoing PCI Added 300mg Clopidogrel and 90mg TicagrelorAdded 300mg Clopidogrel and 90mg Ticagrelor

To continue treatment for 12 monthsTo continue treatment for 12 months

EndpointsEndpoints

Primary endpointPrimary endpointDeath from Vascular causeDeath from Vascular cause

CardiovascularCardiovascular Cerebrovascular Cerebrovascular Unknown causeUnknown cause

Myocardial infarctionMyocardial infarctionStrokeStroke

ResultsResults

18624 patients from 862 centers18624 patients from 862 centersAll patients except for five accounted forAll patients except for five accounted for

Kaplan Meyer Kaplan Meyer

Adverse eventsAdverse events

ConclusionsConclusions

Ticagrelor when compared to Clopidogrel significantly reduces Vascular events and Death.

No significant increase in major bleedingEffects are seen regardless of invasive or

non invasive therapyReversible platelet inhibitionReversible platelet inhibition

Critical AppraisalCritical Appraisal Did the study address a clearly focused question?Did the study address a clearly focused question? Was the assignment of patients randomised?Was the assignment of patients randomised? Were all patients who entered properly accounted for?Were all patients who entered properly accounted for? Was the follow up complete?Was the follow up complete? Were the groups similar at the start of the trial?Were the groups similar at the start of the trial? Were all people involved blind to the treatment?Were all people involved blind to the treatment? Were the groups treated equally aside from the Were the groups treated equally aside from the experimental interventions?experimental interventions? Can the results be applied to my patient care?Can the results be applied to my patient care? Were all clinically important outcomes considered?Were all clinically important outcomes considered? What are the likely benefits are they worth the potential What are the likely benefits are they worth the potential

harm and costs?harm and costs?

Critical appraisalCritical appraisal Did the study address a clearly focused questionDid the study address a clearly focused question Was an inception cohort establishedWas an inception cohort established

Were patients identified at an early and uniform point in the course of their diseaseWere patients identified at an early and uniform point in the course of their disease Were the inclusion criteria clearly specifiedWere the inclusion criteria clearly specified

Was the referral pattern describedWas the referral pattern described Was there likely to be referral biasWas there likely to be referral bias Diagnostic BiasDiagnostic Bias

Was complete follow up achievedWas complete follow up achieved Were all patients entered accounted for in the resultsWere all patients entered accounted for in the results Was the patients clinical status known at the end of the follow upWas the patients clinical status known at the end of the follow up

Were objective outcome criteria developedWere objective outcome criteria developed Was outcome assessment blindWas outcome assessment blind Was adjustment for extraneous prognostic factors carried outWas adjustment for extraneous prognostic factors carried out How large was the likelyhood of the outcome in a specified timeHow large was the likelyhood of the outcome in a specified time How precise was the resultHow precise was the result Will the results help me caring for my patientsWill the results help me caring for my patients

Are the study population similar to our populationAre the study population similar to our population Were all clinical criteria and outcomes consideredWere all clinical criteria and outcomes considered Will the results help with counseling patientsWill the results help with counseling patients

BackgroundBackground

HBA1c historically used for monitoring HBA1c historically used for monitoring DiabetesDiabetes

New ADA guidelines New ADA guidelines Diagnostic tool Diagnostic toolAssociation of HBA1c with Microvascular Association of HBA1c with Microvascular

complicationscomplicationsAdvantagesAdvantages

Higher reproduce ability than FPGHigher reproduce ability than FPGCan be assessed without the patient fastingCan be assessed without the patient fastingPreferred method of monitoring blood glucosePreferred method of monitoring blood glucose

MethodsMethods

Prospective cohort studyProspective cohort studyStudy designed to Study designed to

Compare HBA1C with FPGCompare HBA1C with FPG Risk of Diabetes, IHD, Ischeamic stroke, All cause Risk of Diabetes, IHD, Ischeamic stroke, All cause

mortalitymortality

ARIC populationARIC population 15792 patients from 4 US communities15792 patients from 4 US communities 11stst Visit 1987-9 Visit 1987-9 3 yearly follow up visits3 yearly follow up visits 1990-1992 Blood was stored for HBA1c (Current 1990-1992 Blood was stored for HBA1c (Current

baseline visit)baseline visit)

MethodsMethods

Exclusion criteriaExclusion criteriaPatients that identified themselves as having Patients that identified themselves as having

diabetesdiabetesHistory of Cardiovascular diseaseHistory of Cardiovascular diseaseCardio vascular event between visit 1 and 2Cardio vascular event between visit 1 and 2Non fasting stateNon fasting stateMissing dataMissing data

Final cohort 11092 patientsFinal cohort 11092 patients

EndpointsEndpoints

Assessment of DiabetesAssessment of DiabetesVisit basedVisit basedInterview basedInterview based

Cardiovascular eventsCardiovascular eventsRecords reviewedRecords reviewedPatients reported hospitalization for cardiac events Patients reported hospitalization for cardiac events

on a yearly basison a yearly basisSerial ECGSerial ECG

Statistical AnalysisStatistical Analysis

Model 1Model 1 Adjusted for age, sex, raceAdjusted for age, sex, race

Model 2Model 2 Adjusted for age, sex, race, LDL, HDL, TGl,Adjusted for age, sex, race, LDL, HDL, TGl, BMI, wait to hip ratio, HPT, Family history of DM, BMI, wait to hip ratio, HPT, Family history of DM,

Ethanol use, smoking and physical activityEthanol use, smoking and physical activity Model 3Model 3

All of Model 2 + FPG or HBA1cAll of Model 2 + FPG or HBA1c HBA1C categoriesHBA1C categories

<5.0, 5.0-5.5, 5.5-6.0, 6.0-6.5, >6.5<5.0, 5.0-5.5, 5.5-6.0, 6.0-6.5, >6.5

ResultsResults

ResultsResults

DiscussionDiscussion

HBA1c of >6 is at increased risk of HBA1c of >6 is at increased risk of developing diabetesdeveloping diabetes

HBA1C marker of Cardio vascular riskHBA1C marker of Cardio vascular risk Even after accounted for FPGEven after accounted for FPG

Normal HBA1C can identify non diabetic at Normal HBA1C can identify non diabetic at increased risk of CV diseaseincreased risk of CV disease

J shaped curve for mortality ? CauseJ shaped curve for mortality ? Cause

LimitationsLimitations

Observational studyObservational studySingle HBA1c studySingle HBA1c studyLimited number of FPG during follow upLimited number of FPG during follow upSelf reported DiabetesSelf reported Diabetes

Critical appraisalCritical appraisal Did the study address a clearly focused questionDid the study address a clearly focused question Was an inception cohort establishedWas an inception cohort established

Were patients identified at an early and uniform point in the course of their diseaseWere patients identified at an early and uniform point in the course of their disease Were the inclusion criteria clearly specifiedWere the inclusion criteria clearly specified

Was the referral pattern describedWas the referral pattern described Was there likely to be referral biasWas there likely to be referral bias Diagnostic BiasDiagnostic Bias

Was complete follow up achievedWas complete follow up achieved Were all patients entered accounted for in the resultsWere all patients entered accounted for in the results Was the patients clinical status known at the end of the follow upWas the patients clinical status known at the end of the follow up

Were objective outcome criteria developedWere objective outcome criteria developed Was outcome assessment blindWas outcome assessment blind Was adjustment for extraneous prognostic factors carried outWas adjustment for extraneous prognostic factors carried out How large was the likelihood of the outcome in a specified timeHow large was the likelihood of the outcome in a specified time How precise was the resultHow precise was the result Will the results help me caring for my patientsWill the results help me caring for my patients

Are the study population similar to our populationAre the study population similar to our population Were all clinical criteria and outcomes consideredWere all clinical criteria and outcomes considered Will the results help with counseling patientsWill the results help with counseling patients