Pocket Guide to Anticoagulation in AF

& Dual Antiplatelet Therapy in ACS

Rumi Jaumdally

2015

RJ 2015

CHA2DS2VASc Stroke Risk Score

AF Risk vs Benefit

HAS-BLED Bleeding Risk Score

Coagulation pathway: NOAC

VKA VKA

Inactive Factor

Active Factor

Transformation

Catalysis

X IX

IXa

Thrombin

Xa

Fibrinogen Fibrin

Prothrombin

VIITF VIIa

Initiation

Propagation VKA

Direct Factor Xa inhibitionRivaroxaban/

Apixaban/Edoxaban

Direct Factor IIa inhibitionDabigatran

II

IIa

Spyropoulos AC et al. Expert Opin Investig Drugs 2007;16:431–440 (adapted from)

Anticoagulation pathway

NOAC Pointers

Specific Patient Characteristic

High Risk of bleeding egHAS-BLED >3, Very old

Consider agent/Dose with lowest incidence of bleeding

Dabi 110, Edox, Apix

High Risk of Ischaemic Stroke, low Bleeding Risk

Consider agent/Dose with the best reduction of ischaemic stroke

Dabi 150

Previous Stroke (secondary prevention)

Consider Best Investigated Agent for greatest reduction of 2nd Stroke

Riva, Apix, Edox

CAD, Previous MI or High Risk for ACS-MI

Consider Agent least dependent on renal function

Apix, Edox 30, Riva 15

Concomitant CYP Inhibitors Consider Agents with no/little metabolism via CYP system

Dabi, Edox

Patient Preference Consider once Daily Formulation

Riva, Edox

Date of preparation: July 2012Job code: 1785503

Date of preparation: July 2012Job code: 1785503

Platelet activation mechanisms

Storey RF. Lancet 2009;373:276-278.

The evolution of antiplatelet therapy

ARR = absolute risk reduction; RRR = relative risk reduction

Treatment comparison

ASA vs PlaceboISIS-21

ASA vs ClopidogrelCAPRIE2

ASA + placebo vs Clopidogrel + ASA (UA/NSTEMI)CURE3

ASA + placebo vs Clopidogrel + ASA (STEMI)COMMIT4

ASA + placebo vs Clopidogrel + ASA (STEMI)CLARITY-TIMI 285

Clopidogrel + ASA vs Prasugrel + ASA (scheduled PCI)TRITON-TIMI 386

RRR (primary endpoint)

23%(vascular death)

8.7%(vascular death,stroke + MI)

20%(CV death, non-fatal MI + stroke)

9.2% (death, reinfarction or stroke)

36%(occluded infarctrelated artery,death, + recurrent MI)

19%(CV death, non-fatalMI + stroke)

ARR(primary endpoint)

2.4%(vascular death)

0.5%(vascular death,stroke + MI)

2.1%(CV death, non-fatal MI + stroke)

0.9%(death, reinfarction or stroke)

6.7%(occluded infarctrelated artery,death, + recurrent MI)

2.2%(CV death, non-fatalMI + stroke)

20091998 20111991 2000’s

PrasugrelClopidogrelAspirin Ticlopidine(not available in the UK)

Dual anti-platelet therapy

1980s

1. ISIS-2. Lancet 1998;2:349-360.2. The CAPRIE Steering Committee. Lancet 1996; 348: 1329-1339.3. The CURE Investigators. N Engl J Med 2001;345:494-503.4. Chen ZM, et al. Lancet 2005;366:1607-1621.5. Sabatine MS, et al. N Engl J Med 2005;352:1179-1189.6. Wiviott SD, et al. N Engl J Med 2007;357:2001-2015.

Date of preparation: July 2012Job code: 1785503

Date of preparation: July 2012Job code: 1785503

Ticagrelor treatment also significantly reduced all-cause mortality

Incidence of all-cause mortality* in the PLATO study (secondary endpoint) 1,2

1. Wallentin L, et al. N Engl J Med 2009;361:1045-1057.2. Data on file, AstraZeneca, BRIL/006/NOVA20103. Held C et al. J Am Coll Cardiol 2011; 57(6):762-844. Cannon CP et al. Lancet 2010; 375:283-935. James SK et al BMJ 2011;342:d3527

Ticagrelor significantly reduced the primary endpoint, a composite of cardiovascular death, myocardial infarction or stroke, at 1 year compared with clopidogrel (ARR 1.9%; RRR 16%; p<0.001)

All cause mortality was a secondary endpoint of the PLATO study (nominal p<0.001)1

Mortality benefit was seen consistently across subgroups, including those defined by management strategy (CABG, planned invasive or planned non-invasive)3-5

There was no difference in the incidence of stroke with ticagrelor vs clopidogrel (p=0.22) 1

ARR = absolute risk reduction; RRR = re;lative risk reduction.

Months after randomisation

ARR = 1.4%RRR = 22%

6

4.5

5.9

4

2

00 2 4 6 8 10 12

Cu

mu

lati

ve in

cid

en

ce (

%) Clopidogrel (n=9291)

Ticagrelor (n=9333)

nominal p<0.001