Critical 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 harm and costs? What are the likely benefits are they worth the potential harm and costs?

Background In acute coronary syndromes Dual platelet therapy is the current recommendation In acute coronary syndromes Dual platelet therapy is the current recommendation Current drugs include Asprin and Clopidogrel Current drugs include Asprin and Clopidogrel Clopidogrel Clopidogrel Needs to be Metabolized Needs to be Metabolized Rate and efficacy of this process is slow Rate and efficacy of this process is slow Prasogrel Prasogrel Higher risk of bleeding Higher risk of bleeding

Background Ticagrelor

Methods Double blinded randomized controlled multi centre trial Double blinded randomized controlled multi centre trial Drug superiority trial Drug superiority trial End points End points Vascular events Vascular events Death Death Aztra Zeneca is the sponsor Aztra Zeneca is the sponsor

Methods Inclusion criteria Inclusion criteria Acute coronary syndrome within 24 hrs of onset of symptoms Acute coronary syndrome within 24 hrs of onset of symptoms Exclusion criteria Exclusion criteria Contra indication to Clopidogrel Contra indication to Clopidogrel Fibrinolytic therapy within 24 hrs of randomization Fibrinolytic therapy within 24 hrs of randomization A need for oral anticoagulation therapy A need for oral anticoagulation therapy An increased risk of brady cardia An increased risk of brady cardia P450-3a inhibitor or inducer P450-3a inhibitor or inducer

Methods

Methods Treatment Treatment Randomized to get either ticagrelor or clopidogrel Randomized to get either ticagrelor or clopidogrel Double blind therapy Double blind therapy Ticagrelor Ticagrelor 180mg loading dose 180mg loading dose 90mg twice dly 90mg twice dly Clopidogrel Clopidogrel 300mg loading dose 300mg loading dose 75mg dly 75mg dly If undergoing PCI If undergoing PCI Added 300mg Clopidogrel and 90mg Ticagrelor Added 300mg Clopidogrel and 90mg Ticagrelor To continue treatment for 12 months To continue treatment for 12 months

Endpoints Primary endpoint Primary endpoint Death from Vascular cause Death from Vascular cause Cardiovascular Cardiovascular Cerebrovascular Cerebrovascular Unknown cause Unknown cause Myocardial infarction Myocardial infarction Stroke Stroke

Results patients from 862 centers patients from 862 centers All patients except for five accounted for All patients except for five accounted for

Kaplan Meyer

Adverse events

Conclusions Ticagrelor when compared to Clopidogrel significantly reduces Vascular events and Death. No significant increase in major bleeding Effects are seen regardless of invasive or non invasive therapy Reversible platelet inhibition Reversible platelet inhibition

Critical 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 harm and costs? What are the likely benefits are they worth the potential harm and costs?

Critical appraisal Did the study address a clearly focused question Did the study address a clearly focused question Was an inception cohort established Was an inception cohort established Were patients identified at an early and uniform point in the course of their disease Were patients identified at an early and uniform point in the course of their disease Were the inclusion criteria clearly specified Were the inclusion criteria clearly specified Was the referral pattern described Was the referral pattern described Was there likely to be referral bias Was there likely to be referral bias Diagnostic Bias Diagnostic Bias Was complete follow up achieved Was complete follow up achieved Were all patients entered accounted for in the results Were all patients entered accounted for in the results Was the patients clinical status known at the end of the follow up Was the patients clinical status known at the end of the follow up Were objective outcome criteria developed Were objective outcome criteria developed Was outcome assessment blind Was outcome assessment blind Was adjustment for extraneous prognostic factors carried out Was adjustment for extraneous prognostic factors carried out How large was the likelyhood of the outcome in a specified time How large was the likelyhood of the outcome in a specified time How precise was the result How precise was the result Will the results help me caring for my patients Will the results help me caring for my patients Are the study population similar to our population Are the study population similar to our population Were all clinical criteria and outcomes considered Were all clinical criteria and outcomes considered Will the results help with counseling patients Will the results help with counseling patients

Background HBA1c historically used for monitoring Diabetes HBA1c historically used for monitoring Diabetes New ADA guidelines  Diagnostic tool New ADA guidelines  Diagnostic tool Association of HBA1c with Microvascular complications Association of HBA1c with Microvascular complications Advantages Advantages Higher reproduce ability than FPG Higher reproduce ability than FPG Can be assessed without the patient fasting Can be assessed without the patient fasting Preferred method of monitoring blood glucose Preferred method of monitoring blood glucose

Methods Prospective cohort study Prospective cohort study Study designed to Study designed to Compare HBA1C with FPG Compare HBA1C with FPG Risk of Diabetes, IHD, Ischeamic stroke, All cause mortality Risk of Diabetes, IHD, Ischeamic stroke, All cause mortality ARIC population ARIC population patients from 4 US communities patients from 4 US communities 1 st Visit st Visit yearly follow up visits 3 yearly follow up visits Blood was stored for HBA1c (Current baseline visit) Blood was stored for HBA1c (Current baseline visit)

Methods Exclusion criteria Exclusion criteria Patients that identified themselves as having diabetes Patients that identified themselves as having diabetes History of Cardiovascular disease History of Cardiovascular disease Cardio vascular event between visit 1 and 2 Cardio vascular event between visit 1 and 2 Non fasting state Non fasting state Missing data Missing data Final cohort patients Final cohort patients

Endpoints Assessment of Diabetes Assessment of Diabetes Visit based Visit based Interview based Interview based Cardiovascular events Cardiovascular events Records reviewed Records reviewed Patients reported hospitalization for cardiac events on a yearly basis Patients reported hospitalization for cardiac events on a yearly basis Serial ECG Serial ECG

Statistical Analysis Model 1 Model 1 Adjusted for age, sex, race Adjusted for age, sex, race Model 2 Model 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, Ethanol use, smoking and physical activity BMI, wait to hip ratio, HPT, Family history of DM, Ethanol use, smoking and physical activity Model 3 Model 3 All of Model 2 + FPG or HBA1c All of Model 2 + FPG or HBA1c HBA1C categories HBA1C categories

Results

Results

Discussion HBA1c of >6 is at increased risk of developing diabetes HBA1c of >6 is at increased risk of developing diabetes HBA1C marker of Cardio vascular risk HBA1C marker of Cardio vascular risk Even after accounted for FPG Even after accounted for FPG Normal HBA1C can identify non diabetic at increased risk of CV disease Normal HBA1C can identify non diabetic at increased risk of CV disease J shaped curve for mortality ? Cause J shaped curve for mortality ? Cause

Limitations Observational study Observational study Single HBA1c study Single HBA1c study Limited number of FPG during follow up Limited number of FPG during follow up Self reported Diabetes Self reported Diabetes

Critical appraisal Did the study address a clearly focused question Did the study address a clearly focused question Was an inception cohort established Was an inception cohort established Were patients identified at an early and uniform point in the course of their disease Were patients identified at an early and uniform point in the course of their disease Were the inclusion criteria clearly specified Were the inclusion criteria clearly specified Was the referral pattern described Was the referral pattern described Was there likely to be referral bias Was there likely to be referral bias Diagnostic Bias Diagnostic Bias Was complete follow up achieved Was complete follow up achieved Were all patients entered accounted for in the results Were all patients entered accounted for in the results Was the patients clinical status known at the end of the follow up Was the patients clinical status known at the end of the follow up Were objective outcome criteria developed Were objective outcome criteria developed Was outcome assessment blind Was outcome assessment blind Was adjustment for extraneous prognostic factors carried out Was adjustment for extraneous prognostic factors carried out How large was the likelihood of the outcome in a specified time How large was the likelihood of the outcome in a specified time How precise was the result How precise was the result Will the results help me caring for my patients Will the results help me caring for my patients Are the study population similar to our population Are the study population similar to our population Were all clinical criteria and outcomes considered Were all clinical criteria and outcomes considered Will the results help with counseling patients Will the results help with counseling patients