Antithrombotic Therapy

AT9

What does these guys have in common with the Editor of the 9th ACCP Guidelines on

Antithrombotic Therapy

Seems to be a feature of politicians

Guidelines Oxford English Dictionary

“ A general rule, principle or piece of advice

Oxford Advanced American Dictionary

“Something that can be used to help you make a decision”

Do the 9th ACCP Guidelines conform to these definitions

I think not

  Complex   Confusing   Contradictory   Inconsistent and

  Certainly not

“Something that can be used to help you make a decision”

9th ACCP Guidelines – Grading System

Grading System

 Strong Recommendation 1

 Weak Recommendation 2

 High - quality evidence A

 Moderate - quality evidence B

 Low or very low - evidence C

ACCP Guidelines - 2012 Major Innovations in AT9 1 Unconflicted methodologists as topic editors.

2 Conflicted experts did not participate in final process of making recommendations.

3 Many evidence profile and summary of finding tables.

4 New insights into evidence

(asymptomatic thrombosis, aspirin).

5 Quantitative specification of values and preferences based on systematic review of relevant evidence and formal preference rating exercise.

6 Article addressing diagnosis of DVT.

CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT

Innovation I

•  Unconflicted methodologists as topic editors.

References - 20 First Author Guyatt - 9

Innovation 2

• Conflicted experts did not participate in final process of making recommendations

Innovation 2

Non-experts often non-clinicians

Like asking Lional Messi

Surrogate Outcomes

VTE in Orthopaedic Surgery

Quote

Is this not a bit contradictory ?

Innovation 4

 Asymptomatic thrombosis is of no clinical significance

Who among us will ignore the source of many fatal PE ?

VTE in Orthopaedic Surgery

In patients undergoing THA or TKA, we recommend use of one of the following for a minimum of 10 to 14 days rather than no antithrombotic prophylaxis:

Low-molecular-weight heparin (LMWH), fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose unfractionated heparin (LDUH), adjusted-dose VKA, aspirin

(all Grade 1B) ,

or an intermittent pneumatic compression device (IPCD)

(Grade 1C) .

CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT

ACCP Guidelines – 2012

For patients undergoing major orthopedic

surgery, we suggest extending

thromboprophylaxis in the outpatient period

for up to 35 days from the day of surgery

rather than for only 10 to 14 days

(Grade 2B) .

CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT

ACCP Guidelines – 2012

In patients undergoing THA or TKA, irrespective of the concomitant use of an IPCD or length of treatment, we suggest the use of LMWH in preference to the other agents we have recommended as alternatives: fondaparinux, apixaban, dabigatran, rivaroxaban, LDUH (all

Grade 2B) , adjusted-dose VKA, or aspirin (all

Grade 2C) .

Is this evidence based????

ACCP Guidelines – 2012 Orthopaedic Prophylaxis

What is the basis for this statement? In patients undergoing major orthopedic surgery and who decline or are uncooperative with injections or an IPCD, we recommend using apixaban or dabigatran (alternatively rivaroxaban or adjusted-dose VKA if apixaban or dabigatran are unavailable) rather than alternative forms of prophylaxis (all Grade 1B).

ACCP Guidelines – 2012 Orthopaedic Prophylaxis

VTE in Orthopaedic Surgery

Rivaroxaban Apixaban Edoxaban Dabigatran

Pooled estimates of the results of RCTs comparing oral anticoagulants vs. enoxaparin in THR or TKR

Adapted from Eriksson et al. Annu Rev Med 2011;62:41-57

RE-NOVATE

RE-MOBILIZE

RE-MODEL

RE-NOVATE II Overall

Dabigatran

RECORD3

RECORD2

RECORD1

RECORD4 Overall

Rivaroxaban

ADVANCE-3

ADVANCE-2

ADVANCE-1

Overall

Apixaban

RR=1.03 p=0.58

RR=0.46 p<0.001

RR=0.67 p<0.001

RR=1.09 p=0.66

RR=1.85 p=0.07

RR=0.78 p=0.21

Favours enoxaparin

Favours oral drug

Favours enoxaparin

VTE/all-cause death

Favours enoxaparin Favours oral drug

0.1 1.0 10.0 RR (log scale)

Major bleeding

Favours enoxaparin Favours oral drug

0.1 1.0 10.0 RR (log scale)

Favours oral drug

No head-to-head randomised clinical trials comparing apixaban, rivaroxaban and dabigatran have been performed. Results of indirect comparisons need to be interpreted with caution.

New anticoagulants in THR/TKR

  Dabigatran: as effective and safe vs enoxaparin 40 mg OD; less effective than enoxaparin 30 mg BID; equal bleeding rate

  Rivaroxaban: more efficacious than enoxaparin 40 mg OD/30 mg BID; equal major bleeds but more total bleeds than enoxaparin

  Apixaban: less effective than enoxaparin 30 mg BID; more effective than enoxaparin 40 mg OD; equal major bleeds and less total bleeds than enoxaparin 30 mg BID

Prophylaxis in Orthopaedics

New oral anticoagulants have similar or greater efficacy and safety to LMWH, but are easier to administer New agents will streamline VTE prophylaxis in orthopaedic surgery and will facilitate extended therapy

Venous Thromboembolism

Deep vein thrombosis

Pulmonary embolism

Treatment of VTE ACCP Recommendations 9th Edition   Anticoagulant therapy*

–  Indicated for most patients vs other approaches (grade 2C) –  Initial parenteral anticoagulation (grade 1B)

–  Long-term therapy needed (grade 1B)

–  VKA if no cancer (grade 2C) and INR 2.0 to 3.0 (grade 1B)

  Thrombolytic therapy: IV –  Acute PE + hypotension (grade 2c)

–  Risk of intracranial bleeding: 1% to 3%

  Thrombolytic therapy: catheter – directed –  Highly selected patients with low-bleeding risk

  IVC filter –  Proximal DVT or PE in whom anticoagulants are contraindicated

(grade 1B)

–  If IVC filter is inserted, anticoagulant therapy if bleeding risk resolves (grade 2B)

*Duration of therapy depends on bleeding risk. ACCP = American College of Chest Physicians; INR = international normalized ratio; IV = intravenous.

Kearon C et al. Chest. 2012;141(2 suppl):e419S-e494s.

VTE Treatment Guidelines: Treatment Duration

ACCP 2012

First episode, secondary to a transient risk factor

3 months (grade 1B)

Unprovoked DVT of the leg/PE

≥3 months (grade 1B)

Second unprovoked VTE ≥3 months (grade 1B/2B)

VTE and active cancer ≥3 months* (grade 1B/2B)

*Duration of therapy depends on bleeding risk..

Kearon C et al. Chest. 2012;141(2 suppl):e419S-e494s.

There is no high quality evidence for treatment of VTE

What have we been doing for the last 30 years???

Where did this recommendation come from?

Stroke Prevention in AF

Antithrombotic Therapy

AT9

Need to provide clinicians with guidance

not confusion