The INR: No Need Anymore? Daniel Blanchard, MD Professor of Medicine Director, Cardiology Fellowship Program UCSD Sulpizio Cardiovascular Center

Transcription

1 The INR: No Need Anymore? Daniel Blanchard, MD Professor of Medicine Director, Cardiology Fellowship Program UCSD Sulpizio Cardiovascular Center

2 What is the INR? Tissue Factor (Factor III) is added to patient s plasma Time to clotting (Prothrombin time) is measured Not all batches of TF are the same ISI (international sensitivity index) is calculated based on comparison to a standard TF.

3 The INR: Why Have We Needed It? Metabolism of warfarin varies considerably between patients Vitamin K consumption varies, and affects coagulation TTR is critically important to prevent embolism/bleed TTR in the best anticoagulation clinics is ~65%

4 Wisconsin Anti-Rat Formula arin Wisconsin Alumni Research Foundation arin Do we still need it?

5 #1 Use of Warfarin: Nonvalvular Atrial Fibrillation

6 The NOACs, Chronologically Dabigatran: Pradaxa Rivaroxaban: Xarelto Apixaban: Eliquis Edoxaban: Savaysa

7 Dabigatran: Current Indications Prevention of CVA in pts with nonvalvular Afib 12% reduction in overall mortality vs. warfarin Treatment of DVT and PE following acute therapy with heparin or LMWH DVT/PE prophylaxis/prevention of recurrence

8 Rivaroxaban: Current Indications Prevention of CVA in pts with nonvalvular Afib Treatment of DVT and PE Prevention of recurrence of DVT/PE after initial event DVT prophylaxis after hip/knee replacement

9 Apixaban: Current Indications Prevention of CVA in pts with nonvalvular Afib Significant decrease in CVA and bleeding vs. warfarin DVT prophylaxis with hip/knee replacement Treatment of DVT and PE Reduction of risk of recurrence of DVT and PE

10 Edoxaban: Current Indications Prevention of CVA in pts with nonvalvular Afib Significant decrease in bleeding vs. warfarin Treatment of DVT and PE Reduction of risk of recurrence of DVT and PE Should not be used in patients with creatinine clearance > 95 ml/min because of increased risk of ischemic stroke (about 20% of ENGAGE-AF study population)

11 Currently Available NOACs Dabigatran (Pradaxa) Rivaroxaban (Xarelto) Apixaban (Eliquis) Edoxaban (Savaysa) Trial RE-LY ROCKET AF ARISTOTLE ENGAGE AF # of Patients 18,113 14,264 18,201 21,105 Follow-up (y) CHADS Age >75 (%) Dosing based on renal fx Yes Yes Yes Yes Frequency BID QD BID QD Class DTI FXa inhibitor FXa inhibitor FXa inhibitor

12 Currently Available NOACs: Kovacs, et al. JACC 2015;65:

13 Kovacs, et al. JACC 2015;65:

14 Kovacs, et al. JACC 2015;65:

15 Kovacs, et al. JACC 2015;65:

16 Kovacs, et al. JACC 2015;65:

17 Questions: Warfarin vs. NOACs Do we want blood tests to monitor drug levels? How do we manage peri-procedural anticoagulation? What about use in valvular heart disease? Is aspirin safer in patients with high bleeding risk? How do we treat a bleeding patient?

18 NOACs & Valvular Disease ARISTOTLE: 26% of pts had moderate-severe valvular heart disease or valve repair/biologic replacement (none with moderate or severe MS) Avezum A, et al. Circulation 2015;132:

19 NOACs & Valvular Disease ARISTOTLE: 26% of pts had moderate-severe valvular heart disease or valve repair/biologic replacement (none with moderate or severe MS) Avezum A, et al. Circulation 2015;132:

20 ARISTOTLE: NOACs & Valvular Disease Valve Surgery: Avezum A, et al. Circulation 2015;132:

21 AVERROES Substudy (Apixaban vs. ASA in older pts thought not to be good warfarin candidates) Risk of Major Bleeding Risk of Stroke (!) Ng K et al. Age & Ageing 2015;0:1-7

22 AVERROES Substudy (Apixaban vs. ASA in older pts thought not to be good warfarin candidates) Annual Event Rates for: Stroke/SE Stroke OR major bleeding Ng K et al. Age & Ageing 2015;0:1-7

23 NOAC Antidotes Dabigatran: IV antibody fragment (idarucizumab, Praxbind) has a very high affinity for dabigatran. The anticoagulant effect of Pradaxa is reversed in minutes. Decreases hemorrhage in bleeding pts & those needing urgent surgery* FXa inhibitors: PCC reverses hematologic effects, but has not been tested in bleeding patients. Factor Xa protein decoys under development Andexanet * Pollack CV, et al. NEJM 2015;373:

24 Idarucizumab Eikelboom, et al. Circ 2015;132:2412 Pollack CV, et al. NEJM 2015;373:511

25 Andexanet Modified FXa molecule with a catalytic site mutation: abolishes procoagulant activity of FXa but retains structure Allows Xa inhibitors to bind with strong affinity, neutralizing their anticoagulant activity. Half-life is ~1 hour. Tail of the molecule is modified to prevent factor interactions. Decoy FXa molecule binds direct Xa inhibitors and Xa inhibitors that act through anti-thrombin (Lovenox & fondaparinux). Connors JM. NEJM 2015;373:2471

26 Andexanet Siegal D, et al. NEJM 2015;373:2413

27 Andexanet Siegal D, et al. NEJM 2015;373:2413

28 NOACs Four NOACs are now available In most outcome categories, these agents are equivalent or better than warfarin New information available regarding valvular A Fib

29 Do We Still Need the INR? For better or worse, Yes Today, warfarin is still the anticoagulant of choice for patients with: Mechanical heart valve replacements Severe renal dysfunction/renal failure Mitral stenosis Chronic well-managed warfarin therapy (??) New antidote available for Dabigatran (Praxbind) Antidotes for FXa inhibitors: on the way soon!

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