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Afib training module 4 prophylaxis of stroke in afreview
prophylaxis of stroke in AF
31
Medical
Not Applicable
10/23/2012

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Cards

Term
Warfarin?
Definition

a vitamin K antagonist that has a narrow therapeutic index and its actions are affected by a variety of actors.

Must be monitored

Term
Prothrombin Time
Definition
  • measures the time needed for blood to clot in the presence of thromboplastin and calcium. Most commonly used for warfarin. Values form the PT are calibrated with the international reference preparations to produce an international Normalized ratio (INR) which is used to standardize reporting. INR needs to be determined daily after initial dosing until values stabilize in therapeutic range and after that every 1-4 weeks. Warfarin therapy is dosed to maintain INR from 2 to 3 with a target of 2.5
Term
Does type of AF influence method or degree of antithrombotic therapy?
Definition
NO
Term
what to treatment guidelines recommend in general?
Definition
stratifying patients according to risk level for stroke and basing therapy on this risk. All identify warfarin adn asa as key agents
Term
What do the accf/aha/hars 2011 guide lines use  to determine risk for aF patients
Definition
CHADS2
Term
CHADS2 risk stratification system stands for what? and how many points is each worth?
Definition
  • C = CHF: 1 point
  • H = history of hypertension: 1 point
  • A = 75 years or older: 1 point
  • D = diabetes: 1 point
  • S = history of stroke or TIA: 2 points
Term
ACCF/AHA/HRS 2011 guideline recommendations based on chads 2 scores?
Definition

Low = 0 = ASA 81-325 mg.

Moderate = 1 = ASA or Warf.

High = 2 or more = Warf.

 

UPDATE includes statement that Dabigatran is useful as an alternative to Warfarin and Clopidogrel plus asa may reduce the risk of vascular events.

Term
Chads2 VAsc
Definition

update to chads has the following:

C: = CHF

H: = Hypertension

A: = Age 65-74 (1pt) >75 2pts.

D: = Diabetes

S: = Stroke

V: = Vascular Disease

Sc: = Sex Category = Female 1 pt.

 

Sex: = Female = 1point

D

Term
  • HAS-Bled Scale
Definition

a scale to determine risk of major bleeding:

  1. Hypertension = 1
  2. Abnormal renal and or liver function = 1 point each
  3. stroke = 1
  4. bleeding = 1
  5. labile inrs = 1
  6. elderly (≥65 years) = 1
  7. drugs and /or alcohol = 1

a score ≥ 3 indicates high risk for major bleeding

 

 

Term
What are the clinical trials of Warf vs placebo in af? which was 2ndary prevention?
Definition
  1. AFASAK (copenhagen AF asa and anticoagulation trial)
  2. SPAF I (stroke prevention in AF)
  3. BAATAF (Boston area anti coagulation trial in AF
  4. CAFA (Canadian AF Anticoagulation)
  5. SPINAF Stroke Prevention in Nonrheumatic AF)
  6. EAFT (SECONDARY) European AF
Term
what was the overall risk reduction from a pooled analysis of the 5 primary prevention trials
Definition
68% (4.5% for control vs 1.4% for warf)
Term
what was risk reduction of warfarin compared to ASA?
Definition

38%

absolute risk reduction was 0.7% for primary prevention and 7.0% for 2ndary prevention

Term
Available Anti Thrombotic agents:
Definition
  1. ASA
  2. unfractionoated heparin
  3. warfarin
  4. low molecular weight heparin (not indicated for stroke prophylaxis)
  5. fondaparinux: 
  6. clopidogrel not indicated but guideline note specific use in certain circumstances.
  7. dabigatran
  8. rivaroxaban
Term
does the use of anti arrythmic drugs reduce the potential need for antithromboic theapy?
Definition
NO
Term
What is anti coagulation recommendation in regards to cardioversion?
Definition
3 weeks prior and 4 weeks after
Term

Warfarin Key Facts:

MOA

Definition
warfarin is a vitamin k antagonist it antagonizes or opposes the action of vitamin k and as aresult disrupts the activation of clotting factors II, VII, IX, and X
Term
Anticoagulant effect of warfarin
Definition

generally occurs 24 hours however peak effect may be delayed 72 to 96 hours.

 

Therefore in patients with thrombosis or at high risk fro thrombosis, initial treatment with warfarin is combined with treatment with a rapidly acting parenteral anticoagulant such as heparin or LMWH until the INR has been in the therapeutic range for at least 2 days

Term
POINTS TO REMEMBER re: WARFARIN
Definition
  1. warfarin has a boxed warning regarding bleeding risk
  2. its peak AC effect may be delayed 72 to 96 hours
  3. the close that produces anti coagulation is close to the dose that increases risk for major bleeding (NARROW THERAPEUTIC WINDOW)
  4. INR must be carefully monitored during therapy
  5. genetic factors can affect its action
  6. many drugs, certain foods and herbal supplements can increase or decrease its AC effects.
Term
ASA
Definition
MOA - ASA binds irreversibly to COX which stops the production of TXA2 in platelets. this in turn, reduces platelet aggregation and thrombus formation. because asa irreversibly inactivates COX in platelets the platelet inhibitory effects of asa last the lifespan of the platelet whih is approximately 8 to 10 days.
Term
Dabigatran Etexilate -  MOA
Definition
  1. pro drug that is converted to dabigatran a  direct rhombin inhibitor.
  2. binds to the active site of thrombin both free and clot bound thrombin. prevents the actions of thrombin that is it prevents thrombin from converting fibrinogen to fibrin from activating factors V, VII and XI and from stimulating platelets.
Term
Dabigatran Renal Dosing
Definition

CRCL > 30 ml/min = 150 bid

Severe renal dysfunction : CRCL 15 to 30 = 75mg bid

Patients with CrCL < 15 or on dialysis = no recommendations are provided

Moderate renal impairment crcl 30 - 50 with concomitant use of the p-glycoprotein (p-gp) inhibitor dronedarone (an AAD) or systemic ketoconazole == can be expected to produce dabigatran exposure similar to that seen in severe renal impairment and consideration should be given to reducting the dose to 75MG BID.

 

Term
Dabigatran onset of action and half life
Definition
maximum plasma concentration occurs in 1 to 3 hours, and half-life is 12 to 17 hours.
Term

RELy

what is it?

what were the doses studied?

what were efficacy results?

Definition

key clinical trial for dabigatran

 

compares 150 and 110 prad with warf.

 

significantly reduced primary endpoint of stroke and systemic embolism relative to warfarin

 

Prad 150 (2.2%), warf 3.4% prad 110 3.0%

Term
Safety results of rely?
Definition

                              Dab 150               warf

ICH                          .3%                      .8%

Life Threatening     1.5%                   1.9%

Major Bleed             3.3%                 3.6%

Major GI                  1.6%                 1.1%

Any GI Bleed            6.1%                 4.1%

any bleed                 16.6%               18.4% 

Term

ADVERSE GI EVENTS in RELY

 

Definition

35% vs 24%

discontinuation 2.1% vs 0.6%

Term
  1. Rivaroxaban (Xarelto) MOA
Definition
  1. binds directly to free factor Xa at the factor Xa active site which prevents prothrombin from being converted to thrombin
  2. also binds to Xa that is bound to the prothrombinase complex which prevents clot-associated factor Xa fom converting prothrombin to thrombin
Term
Xarelto Dosing
Definition

orally QD with evening meal.

renal adjustments:

crcl>50 20 mg qd

crcl 15 to 50 = 15 mg qd

crcl <15 = avoid use

Term
ROCKET overview
Definition

Non Inferior to warfarin in terms of composite endpoint of stroke or non-CNS systemic embolism but superiority to warfarin was not demonstrated.  

 

***pi states that there is insufficient experience to dtetermine how rivaroxaban and warfarin compare when warfarin therapy is well controlled.

Term
rocket efficacy results
Definition
2.1 vs 2.4 warf
Term
rocket bleeding events
Definition

major 3.6 vs 3.5

bleeding into critical organ 0.8 vs 1.2

fatal bleeding 0.2 vs 0.5

bleeding requiring transfusion >2 whole units of blood: 1.7 vs 1.3

 

GI 2.0 vs 1.2

Term
rocket adverse reactions
Definition

most common bleeding: 4.3 vs 3.1 

discontinuation similar

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