New Anticoagulants: What to Use What to Avoid

Transcription

1 New Anticoagulants: What to Use What to Avoid Bruce Davidson, MD, MPH Clinical Professor of Medicine Pulmonary and Critical Care Medicine Division University of Washington School of Medicine Seattle USA Relevant financial relationships No honorarium for this talk; room and registration paid by WTS Past honoraria: Bayer and Daiichi-Sankyo Clinical trial activities (Bayer 2, Daiichi- Sankyo 1) Advisory board activities (Bayer/Janssen 2, Daiichi-Sankyo 1) Off-label use: I will discuss Viewing New Anticoagulants 1. Avoid routine use of direct thrombin inhibitors because they lack the cardioprotection of warfarin, anti-xa inhibitors, and heparins Direct thrombin inhibitors: Dabigatran (Pradaxa) Bivalirudin (Angiomax) Argatroban (Arcova) Viewing New Anticoagulants 2. For anticoagulation around medical devices, use heparin or warfarin, and avoid single-factor antagonists Single factor antagonists: Fondaparinux (Arixtra) Direct thrombin inhibitors (dabigatran, bivalirudin, argatroban) Anti-Xa drugs (rivaroxban [Xarelto], apixaban [Eliquis], edoxaban) 1

2 Viewing New Anticoagulants 3. As with antihypertensives, use the best anticoagulant(s) for the niche ICU: Iv for treatment, sq for prophylaxis Sq LMWH or oral anti-xa for stable outpatient DVT initial treatment Tightly controlled warfarin or, if affordable, oral anti-xa for chronic outpatient treatment Fondaparinux or bivalirudin/argatroban for HIT Association of direct thrombin inhibitors with cardiac and medical device thromboses Numbers needed-to-harm (NNH) MI and dabigatran: NNH Vioxx and MI: NNH 239 Stents, valves Dabigatran, valves: NNH 20 Bivalirudin, stents: NNH Dabigatran and MI the rate of myocardial infarction with well-controlled warfarin (for stroke prevention in patients with atrial fibrillation and acute VTE treatment or secondary VTE prevention) is lower than with dabigatran 150 mg twice daily Clemens A et al. Vasc Health Risk Manag. 2013;9:

3 Explosion of the coagulation system Dabigatran, bivalirudin, valves and stents: Contact Activation Pathway For anticoagulation around medical devices, use heparin or warfarin and avoid single-factor antagonists Enoxaparin also failed to protect pregnant woman with mechanical heart valves Single factor antagonists: Fondaparinux (Arixtra) Direct thrombin inhibitors (dabigatran, bivalirudin Anti-Xa drugs (rivaroxban [Xarelto], apixaban [Eliquis], edoxaban) 3

4 As with antihypertensives, use the best anticoagulant(s) for the niche ICU: Iv for treatment, sq for prophylaxis Sq LMWH or oral anti-xa for stable outpatient DVT initial treatment LMWH q 12 h (rather than once-daily) Rivaroxban 15 mg po q 12 h for 3 wk, then 20 mg once daily Apixaban 10 mg po q 12 h for 7 d, then 5 mg bid Edoxaban: Efficacy not proven for VTE treatment (Hokusai NEJM study) High risk: iv UFH Acute PE Intermediate risk: iv UFH (or LMWH q 12 under close observation) Low-risk: LMWH q 12 h for 5 d, or LMWH q 12 h, followed after h by rivaroxaban 15 mg po bid or apixaban 10 mg po bid Chronic outpatient therapy Oral anti-xa drug (rivaroxaban q d or apixaban bid) if affordable, or tightlycontrolled warfarin 4

5 Home-INR-managed warfarin 49% reduction in thrombotic events (95% CI, 15-69%) 67% reduction for patients <55 years old (95% CI, 34-83%) No adverse effects in >85 years old Non-sig reduction in major bleeds and deaths (15%, 95% CI -6 to 23%) C Heneghan, Lancet 2012;379: Covered by all major insurance (except Medicaid) after 1 st month Recommended by ACCP guidelines panel (2B) A Holbrook, CHEST 2012;141: Feb suppl:153s (rec 3.6) Why new oral anti-xa inhibitors may be preferable to warfarin: Fewer intracranial hemorrhages Neurology, 2008 Aspirin for chronic DVT/PE secondary prevention Explosion of the coagulation system 5

6 Aspirin: Extended PE/DVT treatment: 100 mg q AM Recurrent DVT/PE Aspirin (%/yr) Placebo (%/yr) Warfasa 28/205 (6.6) 43/197 (11.2) Aspire 57/411 (4.8) 73/411 (6.5) Avoid routine NSAIDS or aspirin with anticoagulants HR Warfasa: 0.58 ( ; p=0.09) 42% Aspire: 0.74 ( ; p=0.02) 26% Other Placebo rates: 11.6%/yr (apixaban); 11%/yr (dabigatran); 10%/yr (rivaroxaban) JAMA Intern Med 2014 Results Major bleeding Rivaroxaban Events Pt-y Events/100 pt-y Enoxaparin-VKA Events Pt-y Events/100 pt-y NSAID NSAID * * Hemorrhage During Anticoagulant or Antiplatelet Treatment HR = 2.6 ( ) HR = 2.3 ( ) ASA ASA * * HR = 1.5 ( ) HR = 1.5 ( ) * * Significant differences 6

7 Controlling hemorrhage There is minimal evidence Do more than one thing at a time Prioritize saving life; avoid therapeutic paralysis because of lack of evidence Absence of evidence is not evidence of absence Analyzing Hemorrhage Cause Send PT, aptt, PT with 1:1 plasma dilution, CBC with platelet count, cross and type Prothrombin Time: PT prolonged when: -Factor II < 27% (normal range: 75% to 145%) -Factor V < 47% (normal range: 70% to 165%) -Factor VII < 42% (normal range: 65% to 180%) -Factor X < 34% (normal range: 70% to 150%) If 1:1 plasma dilution doesn t correct PT inhibitor (anticoagulant) in plasma Treating important hemorrhage 1. Stop anticoagulant/anti-platelet 2. Analyze cause 3. Give anti-fibrinolytic 4. Can you reverse anticoagulant/antiplt? Protamine, DDAVP, vit K, activated charcoal, hemodialysis 5. Restore hemostasis (FFP, plts, PCCs, rviia) 6. Can you control bleeding site? 7. Maintain Hb around 7.0 g/dl, fibrinogen > 200 mg/dl 8. Monitor frequently Controlling Hemorrhage: General 1.Trauma: Tranexamic acid 1 g iv over 10 min, then 1 g iv over 8 h (cost < US$ 100/dose) 7

8 Controlling Hemorrhage: Investigational Antidotes Triple therapy: DS Ice, Am J Cardiol 2014 Andexanet-alfa for anti-xa anticoagulants Very expensive Xa-mimic molecule by continuous infusion or short-acting bolus Dabi-Fab for dabigatran Monoclonal antibody by bolus in rats Anticoagulants: What to use, what to avoid Avoid routine direct thrombin inhibitors (dabigatran, bivalirudin) Avoid single-factor inhibitors for anticoagulating devices Avoid routine NSAID/aspirin with anticoagulants Use the right anticoagulant(s) in the right niche Anticoagulants: What to use, what to avoid Avoid that State Patrol SOB waiting for me on Rte 2 at Stevens Pass 8