Pocket Guide to Anticoagulation in AF & Dual Antiplatelet Therapy in ACS Rumi Jaumdally 2015 RJ...
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Transcript of Pocket Guide to Anticoagulation in AF & Dual Antiplatelet Therapy in ACS Rumi Jaumdally 2015 RJ...
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