Table 1. Pharmacologic properties of novel oral anticoagulants
Drug |
Standard Dosage |
Reduced Dose |
Oral |
H |
% renal |
Time to peak plasma |
Dabigatran |
150 mg BID |
75 mg BID |
6.5% |
14-17 |
80% |
0.5-2 |
Rivaroxaban |
20 mg daily |
15 mg daily |
80% |
9-13 |
66% |
2-4 |
Apixaban |
5 mg BID |
2.5 mg BID |
66% |
8-15 |
25% |
3 |
Edoxaban |
60 mg or 30 mg |
30 mg or 15 mg |
50% |
9-11 |
35% |
1-2 |
Abbreviations: BID, Twice daily
Table 2. Summary of the important characteristics of the landmark trials of novel oral anticoagulants in atrial fibrillation
Trial name |
Novel oral |
Inclusion criteria(AF and...) |
Common exclusion criteria |
Unique exclusion criteria |
Definition of Valvular |
Mean CHADS2 |
RE-LY |
Dabigatran |
Prior TIA/CVA LV EF 540% or NYHA all last 6 months Age >75 Age 65-74 plus DM, HTN or CAD |
AF secondary to a reversible disorder |
Severe stroke
within 6 months |
Prosthetic valve Hemodynamically relevant valve disease |
2.1 |
ROCKET-AF |
Rivaroxaban |
Prior TIA/CVA or At least two of the following risk factors: -Clinical heart failureor LV EF 53S9S -Hypertension |
Platelet count <90,000/ Severe stroke within 3 months CrCI <30 mlimin ASA >100 mg daily, *ASA and thienopyridine |
Hemodynamically |
|
|
ARISTOTLE |
Apixaban |
Prior TIA/CVA Age 275 Symptomatic CHF or LV EF 4096 Diabetes Hypertension |
ASA>165 mg SCr >2-5 mg/dL CrCI <25 Hgb <9 gidl. |
Moderate or severe
mitral stenosis |
2.1 |
|
AVERROES |
Apixaban |
Age 250, CHADS, 21 or PAD and demonstrated or expected to be unsuitable for warfarin | Thienopyridine Open-label AM discouraged but allowed <100 mg SCr >2.5 mg/dL CrCI <25 mt/rnin |
Valvular disease requiring surgery |
2.0 |
|
ENGAGE AK- |
Edoxaban |
CHAOS, 22 | CrCI <30 ml/min ASA and thienopyridine |
Moderate or severe |
2.8 |
*Subjects with score of 2 limited to 10% of total study population
Abbreviations: AF, atrial fibrillation; TIA, transient ischemic attack; CVA, cerebrovascular accident; LV EF, left ventricular ejection fraction, NYHA, New York Heart Association; DM, diabetes mellitus; HTN, hypertension; CAD, coronary artery disease; PAD, peripheral artery disease; ESRD, end stage renal disease; AC, anticoagulation; CrCI, creatinine clearence; ASA, aspirin; SCr, serum creatinine; Hgb, hemoglobin.
Table 3. Summary of the important outcomes of the landmark trials of novel oral anticoagulants in atrial fibrillation *Not currently approved, awaiting evaluation by FDA
RE-LY |
Dabigatran vs. warfarin |
The 150 mg dose was superior to warfarin for the prevention of stroke | Less hemorrhagic, fatal, ischemic, or disabling stroke Increased risk MI |
Similar major bleeding rates Less ICH, minor bleeding, life-threatening bleeding More GIB |
Strong trend towards all-cause mortality benefit (P=0.051) Less vascular death (P4.04) |
ROCKET-AF Rivaroxaban |
Rivaroxban is noninferior to warfarin for the prevention of stroke | Similar rates of ischemic stroke Less hemorrhagic stroke *Similar rate of MI Less stroke + MI + vascular death |
Similar major and nonmajor bleeding rates Less ICH, critical and fatal bleeding Increased rate of requiring transfusion, more GIB |
Trend towards mortality benefit (P=0.07) |
ARISTOTLE |
Apixaban |
Apixaban was superior to warfarin for the prevention of stroke | Similar rates of ischemic stroke Less hemorrhagic stroke Similar rate of MI |
Less ICH, major and minor bleeding Similar rate of GIB |
Less death from any cause (P=0.047) |
AVER ROES |
Apixaban vs. aspirin |
Early study termination due to clear benefit in favor of apixaban | Less ischemic, disabling or fatal stroke risk Less hospitalization for CV cause Similar hemorrhagic stroke risk |
Similar rates of ICH, GIB, major, fatal and nonmajor bleeding Increased risk of minor bleeding |
Trend towards mortality benefit (P=0.07, study terminated early) |
ENGAGE AF- Edoxaban* TIMI 48 vs. warfarin |
Both doses noninferior to warfarin for the prevention of stroke Less hemorrhagic stroke (both doses) More ischemic stroke with 30 mg dose |
60 mg dose: Lower rate of stroke + CV death or stroke + death Less MACE Similar rate of MI |
Lower rates of bleeding for both doses except 60 mg dose had increased GIB risk | Decreased rate of CV death (both doses)
*Decreased rate of all-cause mortality with 30 mg dose |
Abbreviations: MI, myocardial infarction; CV, cardiovascular; MACE, major adverse cardiac events; ICH, intracerebral hemorrhage; GIB, gastrointestinal bleeding
Table 4. Criteria for Anticoagulant Dose Reduction
Dabigatran |
75 mg BID dose is indicated for a CrCI 15-30 ml/min |
Rivaroxaban |
15 mg dose is indicated for a CrCI 30-49 nnl/min |
Apixaban |
2.5 mg BID dose is indicated if 2 or more of the following are present:
Serum Creatinine 1.5 mg/dL |
Edoxaban |
50% dose reduction for any 1 of the following: |