1. What oral antiplatelet therapy would you choose?
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
What oral antiplatelet therapy would you choose?
ASA alone
ASA + Clopidogrel
ASA + Prasugrel
ASA + Ticagrelor

2. What oral antiplatelet therapy would you choose?
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
What oral antiplatelet therapy would you choose?
ASA alone
ASA + Clopidogrel
ASA + Prasugrel
ASA + Ticagrelor
→ prescribed by ED physician

3. Antithrombotic Therapies in NSTEMI at PresentationII
Antithrombotic Therapies in NSTEMI
at Presentation
Present/
24 hrs (%)
100 44 2 53
ASA
Clopidogrel
Prasugrel
Ticagrelor
Why not ticagrelor?
MD preference or admitting MD selected clopidogrel (17%)
Perceived high bleeding risk (23%)
[advanced age 11%, renal disease 7%, OAC 5%]
Likely needs CABG (7%)
Unpublished data

4. CV Death/MI/Stroke CV Death/MI/Stroke RR 0.81 (0.73-0.90)
ACS patients undergoing PCI
Moderate-to-high risk ACS patients (except those receiving fibrinolysis)
CV Death/MI/Stroke
CV Death/MI/Stroke 12 12
12.1
All-cause Mortality:
5.9% vs. 4.5%
HR 0.78 (0.69–0.89); p<0.001
11.7 10 10
9.9
9.2 8 8
RR 0.81 ( )
HR 0.84 ( ) % 6 6
p=0.0004
p=0.0003 4
TIMI Major Bleeding:
1.8% vs. 2.4%, p=0.03
Non-CABG PLATO Bleeding:
3.8% vs. 4.5%, p=0.026 4 2
Clopidogrel (n=6795) 2
Clopidogrel (n=9291)
Prasugrel (n=6813)
Ticagrelor (n=9333) 3 6 9 12 15 3 6 9 12
Months
Months
Wiviott et al N Engl J Med 2007;357:
Wallentin et al N Engl J Med 2009;361:

5. Non-ST-Segment Elevation ACS Subgroup
CV Death, MI or Stroke
All-cause Death 14 7
Clopidogrel
12.3 12 6
Clopidogrel
5.8 10
Ticagrelor 5 10
Ticagrelor
4.3 8 4
Cumulative incidence (%)
Cumulative incidence (%) 6 3 2 4
HR 0.83 (95% CI 0.74–0.93), p=0.0013 1 2
HR 0.76 (95% CI 0.64–0.90), p=0.002 60
120
180
240
300
360 60
120
180
240
300
360
Days from randomization
Days from randomization
No. at risk
Ticagrelor
5499
5019
4924
4768
3924
2999
2395
5499
5250
5200
5078
4207
3225
2591
Clopidogrel
5581
5152
5036
4888
4056
3112
2471
5581
5343
5283
5165
4307
3328
2651
Lindholm et al Eur Heart J 2014;35:

6. 2012 Focused Update on the Canadian Cardiovascular Society Guidelines for the use of Antiplatelet Therapy
Antiplatelet Therapy for Secondary Prevention in the First Year Following STEMI and NSTEACS
Strong preference for the new ADP receptor inhibitors over clopidogrel (in addition to ASA 81 mg daily) for 1 year
Values & Preferences: Recommendations place greater emphasis on reduction of major cardiovascular events and stent thrombosis vs. an increase in bleeding complications.
Tanguay et al Can J Cardiol 2013:29;

7. Fitchett et al Can J Cardiol 2016;32:S15-34

8. 76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
You are asked to consult on this patient the morning after admission (~12 hours after presentation). She is clinically stable; her ECG is now normal; the 2nd troponin level is higher than the first one.
Would you switch this patient’s P2Y12 receptor inhibitor therapy from clopidogrel to ticagrelor?
Yes No

9. CV Death, MI, Stroke “Early” vs. “Later” Risk
Start of randomised treatment after symptom onset: ~11 hours (median) 8
Hospital
Discharge 8
6.60
Clopidogrel 6 6
Clopidogrel
5.43
5.28
4.77
Cumulative incidence (%) 4
Cumulative incidence (%) 4
Ticagrelor
Ticagrelor 2 2
HR 0.88 (95% CI 0.77–1.00), p=0.045
HR 0.80 (95% CI 0.70–0.91), p<0.001 10 20 30 31 90
150
210
270
330
Days after randomisation
Days after randomisation*
No. at risk
Ticagrelor
9,333
8,942
8,827
8,763
8,673
8,543
8,397
7,028
6,480
4,822
Clopidogrel
9,291
8,875
8,763
8,688
8,688
8,437
8,286
6,945
6,379
4,751
*Excludes patients with any primary event during the first 30 days
Courtesy Lars Wallentin

10. Planned Invasive Stragey: Primary Efficacy Endpoint (CV Death/MI/Stroke) by Clopidogrel Loading Dose
K-M* % at Month 12
Hazard Ratio (95% CI)
Total Pts
Hazard Ratio (95% CI)
p value (Interaction)
Characteristic
Ticag.
Clopid.
Clopidogrel loading dose (Pre-rand. + Study drug)
0.73
<600 mg
9771
9.3
11.2
0.83 ( )
≥600 mg
3634
7.9
9.1
0.87 ( )
0.2
0.5
1.0
2.0
Ticagrelor better
Clopidogrel better
* K-M = Kaplan-Meier estimate
Cannon et al Lancet 2010: 375;283-93

11. Mehta et al Can J Cardiol 2018; doi: 10.1016/j.cjca.2017.12.012

12. Mehta et al Can J Cardiol 2018; doi: 10.1016/j.cjca.2017.12.012

13. Mehta et al Can J Cardiol 2018; doi: 10.1016/j.cjca.2017.12.012

14. Would you switch this patient’s P2Y12 receptor inhibitor therapy from
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
You are asked to consult on this patient the morning after admission (~12 hours after presentation). She is clinically stable; her ECG is now normal; the 2nd troponin level is higher than the first one.
Would you switch this patient’s P2Y12 receptor inhibitor therapy from
clopidogrel to ticagrelor?
Yes No
→180 mg load followed by 90 mg BID

15. Would you refer this patient to coronary angiography?
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
Would you refer this patient to coronary angiography?
Yes No

16. Transferred on day 3 for coronary angiography:
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
Transferred on day 3 for coronary angiography:
90% proximal LAD, 50% proximal Circumflex and 80% OM1, 90% mid- and 60% distal RCA stenoses
2nd generation DES placed in the proximal LAD and mid-RCA
Patients in PLATO undergoing PCI >24 hours after randomization were given an additional dose of study drug (i.e., 90 mg ticagrelor or 300 mg clopidogrel)
Received ticagrelor 90 mg on cath lab table; discharged next day on ASA and ticagrelor 90 mg BID

17. Mehta et al Can J Cardiol 2018; doi: 10.1016/j.cjca.2017.12.012

18. Mehta et al Can J Cardiol 2018; doi: 10.1016/j.cjca.2017.12.012

19. Transferred on day 3 for coronary angiography:
...But what if...?
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
Transferred on day 3 for coronary angiography:
40% proximal LAD, multiple 30-40% proximal and mid Circumflex, 30-50% proximal, mid, and distal RCA stenoses

20. Prior Hypertension, Hyperlipidemia, Smoking
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
Interventional cardiologists opinion: Treat medically
Would you recommend continuing DAPT post-discharge?
Yes No

21. Non-ST-Segment Elevation ACS Subgroup
During the initial 10 days: 74% had angiography, 46% PCI, and 5% CABG*
CV Death, MI or Stroke
All-cause Death
HR 0.73 ( )
Clopidogrel
No revasc
No revasc
Ticagrelor
Interaction p = 0.89
Revasc
Revasc
HR 0.86 ( )
HR 0.75 ( )
*Regardless of revascularization or not, ticagrelor consistently reduced the primary
outcome (HR 0.86 vs. 0.85, Pint=0.93), and all-cause death (HR 0.75 vs. 0.73, Pint=0.89)
Lindholm et al Eur Heart J 2014;35:

22. Non-ST-Segment Elevation ACS Subgroup
Regardless of angiographic severity of disease, ticagrelor consistently reduced the primary outcome (HR 0.87 vs. 0.46, Pint=0.18) and all-cause death (HR 0.80 vs. 0.26, Pint=0.09) with similar risk of major bleeding (HR 1.11 vs. 0.78, , Pint=0.50)
revascularization
Lindholm et al Eur Heart J 2014;35:

23. Prior Hypertension, Hyperlipidemia, Smoking
76 year old female
Prior Hypertension, Hyperlipidemia, Smoking
On Hydrochlorothiazide, Atorvastatin
New onset chest discomfort; 2 episodes in past 24 hours
Heart rate 122/min; BP 170/92 mm Hg, Killip Class I
ECG = ST depression; troponin “positive”
Creatinine 110 mol/L; eGFR 45 ml/min/1.73m2
Hemoglobin 124 g/L
Interventional cardiologists opinion: Treat medically
Would you recommend continuing DAPT post-discharge?
Yes No
→Ticagrelor 90 mg BID