Critical Appraisal
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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