Sandbox: NOAC
Template:A Scientific Statement From the American Heart Association - 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: Arzu Kalayci, M.D. [2]
Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants (NOACs) in the Acute Care and Periprocedural Setting
Comparison Among NOACs
| Dabigatran | Rivaroxaban | Apixaban | Edoxaban | |
|---|---|---|---|---|
| Approved indications | Nonvalular AF ↓ Risk of stroke and systemic embolism | Nonvalular AF ↓ Risk of stroke and systemic embolism | Nonvalular AF ↓ Risk of stroke and systemic embolism | Nonvalular AF ↓ Risk of stroke and systemic embolism. Limitation: should not use in patients with CrCl >95 mL/min as a result of ↑ risk of ischemic stroke compared with warfarin at 60 mg |
| DVT,PE Treatment after 5–10 d parenteral AC ↓ Recurrence Prophylaxis after hip replacement | DVT,PE Treatment ↓ Recurrence Prophylaxis after hip or knee replacement | DVT,PE Treatment ↓ Recurrence Prophylaxis after hip replacement | DVT,PE ↓ Recurrence Treatment after 5–10 d initial parenteral AC | |
| Mechanism of action | Direct thrombin inhibitor | Factor Xa inhibitor | Factor Xa inhibitor | Factor Xa inhibitor |
| Time to peak | 1 h; delayed to 2 h with food | 2–4 h | 3–4 h | 1–2 h |
| Bioavailability | 3%–7% | 10-mg dose: 80%–100% ; 20-mg dose: 66% ; ↑ With food | ~50% | 62% |
| Plasma protein binding | 35% | 92%–95% | ~87% | 55% |
| Volume of distribution | 50–70 L | 50 L | 21 L | 107 L |
| Plasma t½ | 12–17 h;
Elderly 14–17 h; Mild to moderate renal impairment 15–18 h; Severe renal impairment 28 h |
5–9 h;
Elderly 11–13 h |
~12 h (8–15 h) | 10–14 h |
| Metabolism | Hepatic and plasma hydrolysis to active dabigatran;
Hepatic glucuronidation to active metabolites (<10%); P-gp substrate |
Hepatic: oxidation by CYP3A4/5, CYP2J2; hydrolysis to inactive metabolites (51%); P-gp substrate;
No major or active circulating metabolites; Substrate of P-gp and ABCG2 (BCRP) |
Hepatic: 25% mainly by CYP3A4/5; lesser by CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2J2;
O-demethylation and hydroxylation; No active circulating metabolites; Substrate of CYP3A4, P-gp, BCRP |
Minimal CYP3A4 hydrolysis, conjugation, oxidation; Active metabolite (M-4, <10% of parent); P-gp substrate |
| Excretion | Renal (~80%) after IV administration;
After oral, 7% recovered in urine, 86% in feces |
Feces (28%): 7% active, 21% inactive metabolites | Biliary and direct intestinal excretion | Metabolism and biliary/ intestinal excretion accounts for the rest |
| Dosing | ||||
| Nonvalvular AF | CrCl >30 mL/min: 150 mg BID; CrCl 15–30 mL/min:
75 mg BID; CrCl <15 mL/min or on dialysis: Not recommended; CrCl 30–50 mL/min with concomitant P-gp inhibitors: 75 mg BID; CrCl <30 mL/min with concomitant P-gp inhibitors: Avoid coadministration |
CrCl >50 mL/min: 20 mg daily with evening meal; CrCl 15–50 mL/min: 15 mg daily with evening meal;
Not recommended for CrCl <15 mL/min or on dialysis in patients with AF |
5 mg BID;
2.5 mg BID, if 2 of 3 characteristics: Cr ≥1.5 mg/dL, age ≥80 y, weight ≤60 kg |
CrCl >50 to ≤95 mL/min: 60 mg daily; CrCl 15–50 mL/min: 30 mg daily;
NOT recommended for CrCl >95 mL/min |
| DVT or PE treatment | CrCl >30 mL/min: 150 mg BID after 5-10 d parenteral anticoagulation;
CrCl ≤30 mL/min or on dialysis: Not recommended |
15 mg BID with food rst 21 d for initial treatment, then 20 mg once daily with food; Not recommended for CrCl <30 mL/min in patients with DVT or PE | 10 mg BID x 7 d, then 5 mg BID | 60 mg once daily; CrCl 15–50 mL/min or weight ≤60 kg or on certain P-gp inhibitors: 30 mg once daily |
| ↓ in recurrent DVT/PE | CrCl >30 mL/min: 150 mg BID after 5–10 d parenteral anticoagulation;
CrCl ≤30 mL/min or on dialysis: Not recommended |
20 mg daily with food | 2.5 mg BID | |
| DVT,PE prophylaxis after hip or knee replacement | After hip replacement surgery: CrCl >30 mL/min after achievement of hemostasis: If given day of surgery, 110 mg 1–4 h postop;
after day of surgery 220 mg once daily x 28–35 d CrCl ≤30 mL/min or on dialysis: Not recommended CrCl <50 mL/min with concomitant P-gp inhibitors: Avoid coadministration |
Initial dose 6–10 h after surgery provided homeostasis established; 10 mg daily with or without food x 35 d for hip replacement, x 12 d for knee replacement | 2.5 mg BIDx35 d after hip replacement surgery or x 12 d after knee replacement surgery | |
| Additional dosing comments | Avoid use with patients with moderate-severe hepatic impairment (Child- Pugh class B/C) or hepatic disease with coagulopathy; 15-20 mg taken with food; 10 mg with or without food | Not recommended in patients with severe hepatic impairment (Child-Pugh class C) | Not recommended with CrCl <15 mL/min; Not recommended
in patients with moderate-severe hepatic impairment (Child-Pugh class B/C) | |
| Therapeutic measurement | Routine not required, To detect presence: aPTT, ECT (if available), TT; aPTT >2.5 times control may indicate over anticoagulation; Renal function, CBC periodically, at least annually | Routine not required; To detect presence: PT, aPTT, antifactor Xa activity; Renal function, CBC periodically, at least annually;
Hepatic function |
Routine not required; To detect presence: PT, aPTT, antifactor Xa activity;
Renal function, CBC periodically, at least annually |
Routine not required; Prolongs PT, aPTT, antifactor Xa activity;
Renal function, CBC periodically, at least annually |
| AC indicates anticoagulant; AF, atrial brillation; aPTT, activated partial thromboplastin time; BID, twice daily; CBC, complete blood count; CrCl, creatinine clearance; DVT, deep vein thrombosis; ECT, ecarin clotting time; IV, intravenous; NOACs, non–vitamin K antagonist oral anticoagulants; PE, pulmonary embolism; P-gp, P-glycoprotein; PT, prothrombin time; and TT, thrombin time. | ||||