Critical Appraisal

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

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

4. BackgroundTicagrelor

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

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

7. Methods

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

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

10. Results • 18624 patients from 862 centers • All patients except for five accounted for

11. Kaplan Meyer

13. Adverse events

14. 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

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

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

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

19. Methods • Prospective cohort study • Study designed to • Compare HBA1C with FPG • Risk of Diabetes, IHD, Ischeamic stroke, All cause mortality • ARIC population • 15792 patients from 4 US communities • 1st Visit 1987-9 • 3 yearly follow up visits • 1990-1992 Blood was stored for HBA1c (Current baseline visit)

20. Methods • Exclusion criteria • Patients that identified themselves as having diabetes • History of Cardiovascular disease • Cardio vascular event between visit 1 and 2 • Non fasting state • Missing data • Final cohort 11092 patients

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

22. Statistical Analysis • Model 1 • Adjusted for age, sex, race • Model 2 • Adjusted for age, sex, race, LDL, HDL, TGl, BMI, wait to hip ratio, HPT, Family history of DM, Ethanol use, smoking and physical activity • Model 3 • All of Model 2 + FPG or HBA1c • HBA1C categories • <5.0, 5.0-5.5, 5.5-6.0, 6.0-6.5, >6.5

24. Results

25. Results

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

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

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