Patrick Cobb, MD, FACP March 2015 I, Patrick Cobb, MD, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation. I, Patrick Cobb, MD, DO NOT anticipate discussing the unapproved/investigative use of a commercial product/device during this activity or presentation. 1
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Dabigatran Apixaban Rivaroxaban 3
How do they work? How are they different from warfarin? What patients are appropriate for NOACs? Are they safer than warfarin? How do I switch from heparin/warfarin/noac? When do I stop them before surgery? What do I do in case of bleeding? Are they cost-effective? Heparin 4
Low molecular weight heparin Dabigatran 5
Rivoroxaban Apixaban Dabigatran Rivaroxaban Apixaban Target Vitamin K Factor IIa Factor Xa Factor Xa Half life (hr) 40 14-17 5-9 10-14 Monitoring INR None None None Peak effect (hr) 72-96 2 2-4 3-4 Antidote Vitamin K None None None FFP Hemodialysis No Yes No No reversal? Dosing interval Daily BID Daily BID Stroke prevention in non-valvular atrial fibrillation DVT/PE treatment and prevention of recurrence VTE prevention post knee or hip replacement Anticoagulation for prosthetic heart valves Dabigatan Rivaroxaban Apixaban X X X 6
5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Annual stroke rate Placebo Strokes prevented per 1000 patients treated with warfarin 31 Number needed to treat to prevent one stroke: 32 vs 7
Relative Risk: 29,312 NOACs 29,272 warfarin Stroke and embolism 19% All-cause mortality 10% GI bleed 25% 31,830 NOACs 25,661 warfarin Intracranial hemorrhage 51% Stroke or embolism None Relative risk 19% 35,000 30,000 25,000 20,000 15,000 10,000 5,000 Total patients Stroke or embolism NOAC: Number needed to treat to prevent one stroke: 142 Stroke or embolism None - NOAC Absolute risk: NOAC 3.1% 3.8% : ICH No ICH 35,000 30,000 25,000 20,000 15,000 10,000 5,000 - Relative risk 51% NOAC Total patients Absolute risk: NOAC 0.58% 1.24% ICH NOAC: Number needed to treat to prevent one ICH: 152 ICH : No ICH 8
Percent risk of intracranial hemorrhage 20 18 16 14 12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years on therapy NOAC Heparin LMWH NOAC Similar effectiveness compared to warfarin Slightly less GI bleeding More nausea No need for INR testing No long-term data on hypercoagulable patients No data on DVT and malignancy Caution in patients with renal insufficiency 9
Apixaban and dabigatran appear to be similar to LMWH in safety and effectiveness Rivaroxaban may be associated with more GI bleeding than LMWH Oral drugs Less expensive than LMWH 2.3.1. In patients undergoing THA or TKA 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). 10
to NOAC Start NOAC when INR <3 NOAC to warfarin Overlap by at least 3 days, stop NOAC when INR >2 Heparin to NOAC Start after discontinuing drip NOAC to heparin Start drip at scheduled time of next NOAC dose Dabigatran Apixaban, Rivaroxaban Non-life threatening Supportive care Supportive care Normalizes in 12-24 hr in patients with normal renal function Normalizes in 12-24 hr Life-threatening Prothrombin complex concentrate (PCC) Activated PCC Activated FVII Dialysis Prothrombin complex concentrate (PCC) Activated PCC Activated FVII No clinical trial data to support these recommendations DDAVP can be considered Fresh frozen plasma is not effective 11
Atrial fibrillation and DVT therapy (per month) Apixaban $291 Dabigatran $291 Rivaroxaban $286 $80 (including monthly INR monitoring) DVT prophylaxis for orthopedic surgery Several studies show decreased costs for NOACs compared to LMWH At least as effective as warfarin, maybe safer Must use caution in patients with renal insufficiency No antidote, but effects wear off rapidly Encourage compliance Costly drugs More experience needed 12