anticoagulants, vitamin K antagonists
DISEASE INTERVENTION COMPARISON RESULTS
N Engl J Med. 2013 Dec 12;369(24):2304-12 Randomized Controlled Trial, Multicenter Study
IN anticoagulants, vitamin K antagonists, acenocoumarol, phenprocoumon The Use of
pharmacogenetic guided dosing, using CYP2C9 and VKORC1 genotype, combined with clinical information in an algorithm
As Treatment, Acute
Is equal Than
a dosing algorithm that included only clinical variables
To modify the percentage of time that the INR was in the therapeutic range in the first 12 weeks after initiation of therapy
J Am Coll Cardiol. 2012 Aug 28;60(9):861-7 Cohorts
IN anticoagulants, vitamin K antagonists, bleeding risk The Use of
Any of 3 most commonly employed scores: HAS-BLED, ATRIA and HEMORR2 HAGES
As Prognostic Item
Is better Than
no using any risk score
To predict clinically relevant bleeding events, but only with modest performance, being HAS slightly better: c-index: 0.60 HAS-BLED, 0.55 HEMORR(2)AGES, 0.50 ATRIA
Arch Intern Med. 2000 Feb 28;160(4):470-8 Cohorts
IN anticoagulants, vitamin K antagonists The Use of
age > 75 years
As Prognostic Item
Is useful Than
-
To predict bleeding rate (9.9% elders VS 6.6% youngs)
Arch Intern Med. 2010 Sep 13;170(16):1433-41 Cohorts
IN anticoagulants, vitamin K antagonists, antiplatelet drugs, aspirin, clopidogrel, bleeding risk The Use of
aspirin and/or clopidogrel associated to warfarin
As Treatment, Chronic
Is worse Than
warfarin alone
To risk of fatal and nonfatal bleeding: 14% per patient-year with warfarin plus clopidogrel, 16% with warfarin plus aspirin plus clopidogrel
Circulation. 2012 Sep 4;126(10):1185-93 Cohorts
IN anticoagulants, vitamin K antagonists, antiplatelet drugs, aspirin, clopidogrel, bleeding risk The Use of
vitamin K antagonist (VKA) +aspirin +clopidogrel
As Treatment, Chronic
Is worse Than
vitamin K antagonist +1 antiplatelet, or dual antiplatelet therapy with aspirin +clopidogrel
To cause bleeding events, specially in the first 30-90 days: 23 events per 100 person-years with triple therapy, 20 with VKA +1 antiplatelet, 14 with dual antiplatelet. Triple therapy was not more effective than VKA +1 antiplatelet
Am J Med. 2010 Jul;123(7):638-645.e4 Systematic Review
IN anticoagulants, vitamin K antagonists, atrial fibrillation The Use of
frequency of use of anticoagulants, vitamin K antagonists
As Treatment, Chronic
Is worse Than
frequency of use recommended by guidelines
To oral anticoagulants are largely underused in patients with AF and previous AIT or stroke (<70% patients anticoagulated in 25/29 studies, range 19-81%)) or CHADS2 > 2 (<70% patients anticoagulated in 7/9 studies, range 39-92%)
N Engl J Med. 2015 Aug 27;373(9):823-33 Randomized Controlled Trial, Multicenter Study
IN anticoagulants, vitamin K antagonists, atrial fibrillation, periprocedure interruption of anticoagulation The Use of
no bridging anticoagulation, just stopping warfarin 5 days before the procedure and resuming it within 24 hours afterwards
As Treatment, Acute
Is better Than
bridging anticoagulation with full-dose low-molecular-weight heparin (LMWH)
To avoid major bleeding (1.3% just stop Vs 3.2% bridging) while having similar incidence of arterial thromboembolism (0.4% just stop VS 0.3% bridging)
Arch Intern Med. 2004 Oct 11;164(18):2044-50 Cohorts
IN anticoagulants, vitamin K antagonists, bleeding risk, elder patients The Use of
insufficient therapeutic education, polypharmacy, and INR above therapeutic range
As Etiologic risk factor
Is useful Than
no comparison done
To predict increase risk of bleeding: insufficient education ([OR, 8.83), polypharmacy (OR, 6.14), and INR above range (OR 1.08). Low rate of major bleeding despite frequent comobidities and cognitive impairment: 2.4 events per 1000 patient-months
J Thromb Haemost. 2016 Sep;14(9):1715-24 Cohorts
IN anticoagulants, vitamin K antagonists, bleeding risk, elder patients The Use of
Any of 3 most commonly employed scores: HAS-BLED, ATRIA and HEMORR2 HAGES
As Prognostic Item
Is bad Than
no comparison here
To predict major bleeding: All three scores were associated with major bleeding in the elderly, but had poor predictive abilities: C-statistics < 0.60 all. Only 2 (anemia and antiplatelet therapy) of the classical risk factors were associated with bleeding
J Am Coll Cardiol. 2011 Jan 11;57(2):173-80 Cohorts
IN anticoagulants, vitamin K antagonists, bleeding risk, elder patients The Use of
HAS-BLED score: Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (1 point each, 0 = low risk, 1-2 = moderate, >=3 = high risk)
As Prognostic Item
Is better Than
other available scores
To predict risk of major haemorrhage under chronic warfarin: low risk 0.9% per patient-year, moderate 3.7%, high 6.7%.
J Gen Intern Med. 2005 Nov;20(11):1008-13 Cohorts
IN anticoagulants, vitamin K antagonists, bleeding risk, elder patients The Use of
outpatient bleeding risk index (BRI): 1 point for: age>65, history of stroke, history gastrointestinal bleeding, any of following (diabetes, recent myocardial infartion, anemia, creat>1.5mg/L)
As Prognostic Item
Is useful Than
intuitive assesment of bleeding risk
To predict risk of major haemorrhage under chronic warfarin: high-risk 10.6% per patient-year, intermediate 2.5%, and low-risk only 0.8% per year.
Lancet. 2016 Jun 04;387(10035):2302-2311 Randomized Controlled Trial, Multicenter Study
IN anticoagulants, vitamin K antagonists, direct oral anticoagulants, bleeding risk The Use of
a new bleeding risk score : ABC-bleeding : age, previous bleeding, haemoglobin, high-sensitivity cardiac troponin T and growth differentiation factor-15 (GDF-15)
As Prognostic Item
Is better Than
other bleeding risk scores, HAS-BLED, ORBIT
To predict the risk of major bleeding at 1 year for patients on warfarin, apixaban or dabigatran
Ann Intern Med. 2009 Mar 3;150(5):293-300 Randomized Controlled Trial, Multicenter Study
IN anticoagulants, vitamin K antagonists, excessive anticoagulation, without major bleeding The Use of
low dose oral vitamin K (1.25mg)
As Treatment, Acute
Is equal Than
placebo
To reduce any bleeding (15.8% vit VS 16.3% placebo) or major bleedings (2.5 % vit K VS 1.1% placebo)
Arch Intern Med. 2003 Nov 10;163(20):2469-73 Randomized Controlled Trial
IN anticoagulants, vitamin K antagonists, excessive anticoagulation, without major bleeding The Use of
oral vitamin K1 (2.5mg if INR 6-10, 5mg if INR > 10)
As Treatment, Acute
Is equal Than
intravenous vitamin K1 (0.5mg if INR 6-10, 1mg if INR > 10)
To correct INR: response to intravenous phytonadione was more rapid at 6 and 12 hours, but at 24 hours INR values were similar for both groups and more patients in the IV group were overcorrected (INR < 2: 8.7% in PO group VS 29% in IV group)
Lancet. 2006 Feb 4;367(9508):404-11 Meta-Analysis
IN anticoagulants, vitamin K antagonists, monitoring The Use of
patient self-monitoring of anticoagulation
As Dosage Scheme
Is better Than
standard monitoring by a health professional
To reduce thromboembolic events (OR 0.45, NNT aprox 38), all-cause mortality (OR 0.61, NNT aprox 67), and major haemorrhage (OR 0.65, NNT aprox 67)
Ann Intern Med. 2011 Apr 5;154(7):472-82 Meta-Analysis
IN anticoagulants, vitamin K antagonists, monitoring The Use of
patient self-monitoring of anticoagulation, with or without self-management
As Dosage Scheme
Is better Than
usual care and monitoring by a health professional
To reduce thromboembolic events (OR 0.58) and total mortality (OR 0.74), with no excess of major bleedings (OR 0.89)
BMJ. 2002 Nov 9;325(7372):1073-5 Descriptive
IN anticoagulants, vitamin K antagonists, monitoring The Use of
INR values in excess
As Prognostic Item
Is useful Than
No control
To hight INRs are associated with an excess mortality. With an increase of 1 unit of INR above 2.5, the risks of death from cerebral bleeding (149 deaths / 42 451 patients) and from any cause were about doubled
N Engl J Med. 2008 Mar 6;358(10):999-1008 Descriptive
IN anticoagulants, vitamin K antagonists, warfarin The Use of
genetic variants of vitamin K epoxide reductase (VKORC1), the target of warfarin
As Diagnostic Tool
Is better Than
genetic variants of cytochrome P-450 2C9 (CYP2C9), which metabolises warfarin
To predict the time to the first INR within the therapeutic range or in excess
Circulation. 2007 Nov 27;116(22):2563-70 Randomized Controlled Trial
IN anticoagulants, vitamin K antagonists, warfarin The Use of
pharmacogenetic guided dosing, using CYP2C9 and VKORC1 genotype
As Dosage Scheme
Is equal Than
standard empirical dosing
To reduce time of out-of-range INR (31% genotyping VS 33% standard) or proportion of patients reaching therapeutic INR at day 5 or 8.
J Am Coll Cardiol. 2011 Feb 1;57(5):612-8 Cohorts
IN anticoagulants, vitamin K antagonists, warfarin The Use of
pharmacogenetic guided dosing, using CYP2C9 and VKORC1 genotype, combined with clinical information in a formal algorithm
As Dosage Scheme
Is better Than
methods using only clinical information (empiric or a formal clinical algorithm), or methods using only genetic data
To improve the proportion of patients whose predicted doses were within 20% of their actual therapeutic doses: 52% pharmacogenetic algorithm, 43% genetic data, 39% clinical algorithm, 37% empiric dosing.
N Engl J Med. 2005 Jun 2;352(22):2285-93 Clinical Trial (non-controlled, non-randomized)
IN anticoagulants, vitamin K antagonists, warfarin The Use of
vitamin K epoxide reductase complex 1 (VKORC1) haplotipes
As Dosage Scheme
Is useful Than
no comparison here
To stratify patients into low-, intermediate-, and high-dose warfarin groups
N Engl J Med. 2013 Dec 12;369(24):2283-93 Randomized Controlled Trial, Multicenter Study
IN anticoagulants, vitamin K antagonists, warfarin The Use of
pharmacogenetic guided dosing, a dosing algorithm that included both clinical variables and genotype data
As Treatment, Acute
Is equal Than
a dosing algorithm that included only clinical variables
To modify the percentage of time that the INR was in the therapeutic range from day 4 through day 28 of therapy
N Engl J Med. 2013 Dec 12;369(24):2294-303 Study type to be defined
IN anticoagulants, vitamin K antagonists, warfarin The Use of
pharmacogenetic guided dosing, using CYP2C9 and VKORC1 genotype, combined with clinical information in an algorithm
As Treatment, Acute
Is better Than
standard empirical dosing of warfarin
To improve the percentage of time that the INR was in the therapeutic range in the first 12 weeks after initiation of therapy: 67% with pharmacogenetics VS 60% clinical
Ann Intern Med. 2003 May 6;138(9):714-9 Randomized Controlled Trial
IN anticoagulants, vitamin K antagonists, warfarin, thromboembolic disease The Use of
higher starting dose: 10 mg/day
As Treatment, Acute
Is better Than
usual starting dose: 5 mg/day
To reduce time to achieve therapeutic INR at day 5 (83% with 10mg VS 46% with 5mg, overall reduction by 1.5 days). No significant differences in major bleeding, coagulation excess (INR > 5.0), recurrent events and survival.
Stroke. 2009 Apr;40(4):1410-6 Meta-Analysis
IN atrial fibrillation, anticoagulants, vitamin K antagonists, bleeding risk, elder patients, stroke, ischemic, cerebral infarction, embolic The Use of
age
As Etiologic risk factor
Is useful Than
-
To predict an increased risk of stroke (HR per decade 1.45), major bleeding (HR per decade 1.61) and cardiovascular events (HR per decade 1.45). However the relative benefit of warfarin for preventing stroke persisted, while that of aspirin decreased
Lancet. 2007 Aug 11;370(9586):493-503 Randomized Controlled Trial, Multicenter Study
IN atrial fibrillation, elder patients, not high haemorrahgic risk, not high stroke risk, anticoagulants, vitamin K antagonists, bleeding risk, elder patients The Use of
warfarin, antivitamin K
As Treatment, Chronic
Is better Than
aspirin
To reduce all-type strokes: 1.8% warfarin versus 3.8% aspirin. No increase at all in major haemorrhages.