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 The problem with Warfarin: 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 The NOACs All indicated for: CVA prevention in nonvalvular AFib Treatment of DVT/PE (after initial parenteral therapy with dabigatran and edoxaban) DVT/PE prophylaxis/prevention of recurrence (except edoxaban)

8 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

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

10 Kovacs, et al. JACC 2015;65:

11 Kovacs, et al. JACC 2015;65:

12 Questions about NOAC s All of these results are from industry-sponsored clinical trials What about real-world results?

13 Efficacy Safety

14 Efficacy (Stroke/Systemic Embolus) (Data from a large US insurance [Optum] database, ) Noseworthy, et al. CHEST 2016;150:

15 Safety (Major Bleeding) Noseworthy, et al. CHEST 2016;150:

16 Major Bleeding Noseworthy, et al. CHEST 2016;150:

17 Questions: Warfarin vs. NOACs Do we want blood tests to monitor drug levels? TEG 6s and anti-xa assays detect presence of NOAC very accurately, but don t yet have therapeutic ranges What about use in valvular disease and CKD? Is aspirin safer in patients with high bleeding risk? What about antidotes?

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 Siontis, et al. Circulation 2017;135:714-6.

20 NOACs in Renal Dysfunction NOAC use is growing in this population: Why?

21 NOACs in Renal Dysfunction: Variable Renal Excretion

22 NOACs in Renal Dysfunction: How Do They Compare to Warfarin?

23 NOAC s & Renal Disease

24 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

25 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 (K-centra) reverses hematologic effects, but has not been tested in bleeding patients. Factor Xa protein decoys Andexanet (Annexa) * Pollack CV, et al. NEJM 2015;373:

26 Andexanet Modified FXa molecule: Xa inhibitors bind with strong affinity, neutralizing their anticoagulant activity. Molecule tail modification prevents interaction with other factors. Decoy recombinant FXa molecule binds all Xa inhibitors (including Lovenox & fondaparinux). Connors JM. NEJM 2015;373:2471

27 Andexanet: ANNEXA-4 67 patients on factor Xa inhibitors with acute major bleeding All treated with bolus and infusion Andexanet Effective hemostasis in ~80% of patients Thrombotic events occurred in 18% in the 30-day follow-up Connolly, et al. NEJM 2016;375:

28 Andexanet: ANNEXA-4 Connolly, et al. NEJM 2016;375:

29 NOACs Four NOACs are now available In most outcome categories, these agents are equivalent to or better than warfarin New information available regarding Valvular A Fib Renal dysfunction Antidotes

30 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 replacement Mitral stenosis Severe renal dysfunction/renal failure (??) Chronic well-managed warfarin therapy (??) New antidote available for Dabigatran (Praxbind) Antidotes for FXa inhibitors: on the way soon!

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