AF part 2 - prevention of clot Flashcards
Antithrombotic Options: AF
ASA, Warfarin, ASA + Clopidogre
Efficacy:
u ASA reduces risk of ischemic stroke by 19%
u Warfarin reduces risk of stroke by 64%
u ASA + Clopidogrel are more effective than ASA, but not as effective as warfarin
Safety:
u Bleeding is higher with Clopidogrel + ASA than either ASA alone or Warfarin alone
ASA + Clopidogrel
not best treatment
options
Assessment of Thromboembolic
Risk: CHADS2 Score
goal: Prevention of Cardioembolic Stroke and Systemic Embolism
u Patients with NVAF have ~ 4.5% risk of stroke/year
u Incidence of stroke rises with considerably with
addition of risk factors
C Congestive Heart Failure 1 H Hypertension 1 A Age > 75 1 D Diabetes 1 S Prior Stroke or TIA 2
CHADS2 Score: Annual Stroke Rate: 0 1.9% 1 2.8% 2 4.0% 3 5.9% 4 8.5% 5 12.5% 6 18.2%
CHA2DS2-VASc is used for lower risk patients
(CHADS2 score of 0) to further quantify risk
not used much
only diff is 2 for age >75
we only use when the pt chad score is 0
C Congestive Heart Failure 1 H Hypertension 1 A Age > 75 2 D Diabetes 1 S Prior Stroke or TIA 2 V Vascular Disease 1 A Age > 65 but < 75 1 Sc Sex criteria – Female 1
CHADS 65 score
CLOT RISK ASSESSMENT DETERMINES TREATMENT SELECTION, not really bleed rsik
CHADS 65 score increases risk out of CHADSVASc
age 65-74
The “CCS Algorithm” (“CHADS 65”) for
Stroke Prevention in Non-Valvular AF
Age ≥ 65 years -> OAC
Prior Stroke or TIA or Hypertension or Heart failure or Diabetes Mellitus (CHADS2 risk factors) = OAC
Coronary or Peripheral Arterial Disease
= Antiplatelet therapy
None of those
No Antithrombotic
1A DOAC is preferred over warfarin
2Therapeutic options include ASA 81 mg daily
alone, clopidogrel 75 mg daily alone, or ASA 81
mg daily in combination with either clopidogrel
75 mg daily, ticagrelor 60 mg bid, or rivaroxaban
2.5 mg bid (depending on clinical circumstance)
HASBLED Bleeding Risk Score
know what each risk factor is
used to closely monitor pt but not determine tx selection
Hypertension (SBP>160 mm Hg) 1
Abnormal renal function (Cr>200 umol/L) or liver function (cirrhosis, bilirubin >2x upper normal, or
AST/ALT/ALP >3 x upper normal
Stroke history 1
Bleeding (major) or tendency (prior GI bleed, PUD, prior cerebral hemorrhage)
Labile INR (unstable INR, time in therapeutic range <60%)
Elderly: Age >65 years 1
Drugs (antiplatelet, NSAIDS, antiinflammatory medications, steroids); alcohol or drug abuse that can influence bleed risk
score of three or more, you can see, by the bar graph starts to really increase of patients risk.
But we never use a has blood score to say note we’re not going to add anticoagulate this patient.
Antithrombotic Options: AF
ASA
WARFARIN
ASA + CLOPIDOGREL
NOAC/DOAC (Novel/Direct Oral AntiCoagulant) DABIGATRAN RIVAROXABAN APIXABAN EDOXABAN
Anticoagulation:
What effect am I looking for?
How can I determine if
therapy is safe?
Efficacy Outcomes:
• Prevention of Cardioembolic
Stroke / Ischemic Stroke
Safety Outcomes:
• Major bleeding especially
Intracranial hemorrhage (ICH) - focus on ICH as it has higher risk mortality
ASA for AF
Stroke
Prevention
Warfarin for AF
Stroke
Prevention
ASA ischemic stroke RRR = 19%
warfarin RRR = 64%, Rate of major hemorrhage: Warfarin = 1.3%; Control = 1% (NS) RRR = 64%, P < 0.001 incidence of ischemic stroke reduced from 4.5% to 1.4% per year (warfarin(
ACTIVE W and ACTIVE A Trials
ASA + Clopidogrel
ACTIVE W: All these patients had a fib and a Chad score about least 1
ACTIVE A: AF with ≥ 2 episodes in last 6 months + CHADS2 score of
≥ 1 or PVD or CAD that were “unsuitable for warfarin
ACTIVE W: trial was ended early due to superiority of warfarin over ASA +
clopidogrel
Risk of major bleeding was also higher with clopidogrel + ASAthan warfarin (RR = 1.1; CI 83-1.45)
ACTIVE A:
Major vascular events were reduced with ASA + clopidogrel (RR = 0.89, CI 0.81-0.98, p = 0.01)
Risk of major bleeding was higher in ASA + clopidogrel than in
the ASA alone arm (RR = 1.57; CI 1.29-1.92, p<0.01)
Antithrombotic Options: AF
ASA, Warfarin, ASA + Clopidogre
Efficacy:
u ASA reduces risk of ischemic stroke by 19%
u Warfarin reduces risk of stroke by 64%
u ASA + Clopidogrel are more effective than ASA, but not as effective as warfarin
Safety:
u Bleeding is higher with Clopidogrel + ASA than either ASA alone or Warfarin alone
ASA + Clopidogrel
not best treatmentptions
Dabigatran vs. Warfarin:
RE-LYu NVAF + additional risk factor
u Excluded: valvular AF, CRCL < 30mL/min, condition ↑ing bleed risk, stroke <14 days or severe stroke < 6 months
INR values in
therapeutic range 64% of time
65% of the time INR in therapetuic range considered good control
open label randomized pt to doses 110 or 150 dabig
Dabigatran 150mg po bid is superior to warfarin
with a non-significantly lower rate of major bleeding
- Dabigatran 150mg bid had significantly lower ICH
- Dabigatran 150mg po bid had significantly higher rate of GI bleed (made in tartaric acid environment for prodrug to release the durg)
AVOID IN PT WTIH PREVIOUS GI BLEED AND PT ON PPI THAT MAY NOT HAVE GOOD ABSORPTION (DECREASED ACIDIC ENV)
Both doses of dabigatran had higher rates of MI than
warfarin (CHOOSE DIFF DOAC?)
Rivaroxaban vs. Warfarin:
ROCKET AF
NVAF with CHADS2 score of ≥ 2
Excluded: valvular AF, CRCL < 30mL/min, hemorrhagic
related concerns, GI bleed < 6 months, BP > 180/100,
stroke < 3 months, TIA < 3 days, ASA > 160mg/day, chronic
NSAID use
In patients randomized to warfarin, INR values in
therapeutic range 55% of time
not as well controlled as dabig
bottom line
Rivaroxaban 20mg daily*
(OR 15mg daily if CRCL 30-49mL/min)
Warfarin* (target INR 2-3)
How effective is the
comparator? 55% in range
Rivaroxaban is non-inferior to warfarin
with similar rates of bleeding
Major Bleeding:
u Rivaroxaban had a significantly lower rates of ICH
u Rivaroxaban had a significantly higher rate of GI bleed
Apixaban vs. Warfarin:
ARISTOTLE
NVAF or Atrial Flutter + ≥1 CHADS2 risk factor
Excluded: mechanical heart valves, severe renal
insufficiency
In patients randomized to warfarin, INR values in
therapeutic range 66% of time
apix 5mg bid or ____________? vs warfarin
* 2.5mg po bid used if ≥ 2 of: ≥ 80 years weight ≤ 60kg SCR ≥ 133 µmol/L
* 2.5mg po bid used if ≥ 2 of: ≥ 80 years weight ≤ 60kg SCR ≥ 133 µmol/L
Apixaban is superior to warfarin
with a significantly lower rate of major bleeding
ONLY DOAC SHOWING SUPERIORITY
Apixaban has a significantly lower rate of ICH
u Apixban has a similar rates of GI bleeding
Edoxaban vs. Warfarin
ENGAGE AF-TIMI 48
NVAF or Atrial Flutter + ≥2 CHADS2 risk factor
u Excluded: moderate to severe mitral stenosis, CRCL <
30mL/min, ACS or stroke in past 30 days, use of dual
antiplatelet therapy
In patients randomized to warfarin, INR values in therapeutic
range 68.4% of time
Edoxaban* 60mg po daily
30mg po daily
(1/2 dose used if CRCL 30-50mL/min, wt < 60kg,
concomitant use of verapamil or quinidine)
Warfarin
Edoxaban 30mg daily is non-inferior to warfarin but event rate was higher than warfarin;
Edoxaban 60mg po daily is non-inferior to warfarin with a significantly lower rate of major bleeding
see slide 42can you say that dabug is better than rivaroxaban?
no as trials arent head to head
Retrospective Cohort Trial
