Practical Guide to the use of
Oral Anticoagulants (NOACs)
Direct thrombin inhibitor
DABIGATRAN Pradaxatm
110 mg and 150 mg capsules*
Direct Xa factor inhibitors
RIVAROXABAN 101010 Xareltotm
1515 15
20 20 20
10 mg, 15 mg and 20 mg tablets*
APIXABAN Eliquistm
2.5 mg and 5 mg tablets* Capsules and tablets are shown at actual size.
*
Faculté de médecine
TABLE OF CONTENTS 04 Indications, Dosages, Exception Codes, and RAMQ Reimbursement Criteria
06
Table of Dose Adjustment Based on Renal Function
07
Precautions and Contraindications
08
Pharmacokinetic Parameters
09
Potential Interaction Mechanisms
10
D rug Interactions Impact on NOAC Plasma Concentrations
14
Drug Administration
15
Monitoring NOAC-treated Patients
16
Switching from One Agent to Another
18
NOAC Management Before and After Surgery
21
Bleeding Management
22
Measuring Anticoagulant Effect
23
2014 CCS Recommendations CHADS2 and HAS-BLED Scores
Information and Pharmacology
INDICATIONS, DOSAGES, EXCEPTION CODES AND RAMQ REIMBURSEMENT CRITERIA INDICATION
DRUG AND DOSAGE2
Prevention of stroke and systemic embolism in patients presenting nonvalvular atrial fibrillation (AF)1
DABIGATRAN 150 mg PO BID Administer 110 mg PO BID if - High risk of bleeding3 OR Age 80 OR Weight 50 kg RIVAROXABAN 20 mg PO DIE Administer 15 mg PO DIE if CrCL 30-49 ml/min APIXABAN 5 mg PO BID Administer 2.5 mg PO BID if TWO of the following criteria - Age 80 - Weight 60 kg - Creatinine 133 mol / L DABIGATRAN 150 mg PO BID Start AFTER anticoagulant treatment (LMWH4 or IV Heparin) administered parenterally for 5 to 10 days Administer 110 mg PO BID if - High risk of bleeding3 OR Age 80 OR Weight < 50 kg RIVAROXABAN 15 mg PO BID5 X 3 weeks, then 20 mg PO DIE No dose adjustment required if CrCL: 30-49 ml/min
Treatment of deep vein thrombosis (DVT) OR pulmonary embolism (PE)
Note: It is not necessary to start initial treatment either LMWH4 or IV Heparin
APIXABAN 10 mg PO BID5 X 7 days, then 5 mg PO BID X 6 months, then 2.5 mg BID if continuing treatment No dose adjustment required if CrCL: 30-49 ml/min Note: It is not necessary to start initial treatment either LMWH4 or IV Heparin
Prevention of venous thromboembolism (VTE) in patients having total hip or knee replacement
DABIGATRAN 110 mg STAT, then 220 mg PO DIE Hip: 28 to 35 days - Knee: 10 days RIVAROXABAN 10 mg PO DIE Hip: 35 days Knee: 10 to 14 days APIXABAN 2.5 mg PO BID Hip: 32 to 38 days - Knee: 10 to 14 days
NOACs are preferable to warfarin for patients with non-valvular AF (ABSENCE of mechanical valve prosthesis, rheumatic mitral stenosis, bioprosthesis, or mitral valve repair). 2 Initiation of NOAC treatment is not recommended in patients with altered renal function and a creatinine clearance rate (CrCL) < 30 ml/min. 1
04
INFORMATION AND PHARMACOLOGY
EXCEPTION CODE CV-155
REIMBURSEMENT CRITERIA (RAMQ) - Anticoagulation with a vitamin K antagonist (VKA)(warfarin or nicoumalone) not in the desired therapeutic range OR - Monitoring of VKA anticoagulation is not possible or is not available
-
-
CV-157 (DVT) CV-165 (PE)
Patients who cannot receive treatment consisting of heparin followed by a VKA Authorization period for DVT: 6 months Note: All authorization requests for treatment beyond 6 months must be submitted using the exceptional patient form or via the Internet.
-
Authorization period for PE: long term CV-169: treatment for venous thromboembolism (VTE or PE). This code provides access to reimbursement for 10 mg BID for the first 7 days following treatment, and 5 mg BID for up to 6 months. CV-170: for preventing recurrence of venous thromboembolism (VTE or PE) in patients who have been treated with anticoagulant therapy for 6 months or longer after an acute episode of idiopathic venous thromboembolism. This code provides access to reimbursement for 2.5 mg BID for 12 months, up to a maximum of 730 tablets. -
CV-127 (Hip)
Authorization period: 35 days
CV-169 CV-170
CV-126 (Knee) Authorization period: 14 days Consider high risk of bleeding in the presence of a CrCL 30â&#x20AC;&#x201C;49 ml/min, gastro-intestinal ulcer, recent surgery, significant drug interaction, etc. LMWH: Low molecular weight heparin. 5 For patients already started on another molecule for > _ 48 hours (e.g., warfarin or parenterally administered anticoagulant), refer to a specialist to determine the best dose of rivaroxaban or apixaban. 3
4
INFORMATION AND PHARMACOLOGY
05
TABLE OF DOSE ADJUSTMENT BASED ON RENAL FUNCTION
RENAL FUNCTION (CrCL) 50 ml/min
AF: 20 mg DIE
AF: Reduce to 15 mg DIE
RIVAROXABAN
DABIGATRAN
Reduce to 110 mg PO BID if - High risk of bleeding OR - Age 80 OR - Weight < 50 kg
DVT/PE: 15 mg BID X 3 wk., then 20 mg DIE
AF: 5 mg BID2
APIXABAN
30-49 ml/min
150 mg BID1
DVT/PE: 10 mg BID X 7 days, then 5 mg BID X 6 months
< 30 ml/min
< 25 ml/min
DVT/PE: dose unchanged
AF: Reduce to 2.5 mg PO BID if TWO of the following criteria presentâ&#x20AC;&#x2030;2 - Age 80 - Weight 60 kg - Creatinine 133 mol/L DVT/PE: dose unchanged
_ 80, weight < 50 kg, or with high risk of bleeding) to It is sometimes necessary (patients age > _ 50 ml/min. reduce the dose of dabigatran to 110 mg BID, even if Clcr > In treating AF, it sometimes necessary to reduce the dose of apixaban to 2.5 mg BID _ (when 2 adjustment criteria are present), even if Clcr > 50 ml/min.
1
2
06
INFORMATION AND PHARMACOLOGY
PRECAUTIONS AND CONTRAINDICATIONS
WARFARIN
DABIGATRAN RIVAROXABAN APIXABAN
Severe renal failure (CrCL < 30 ml/min OR acute renal failure1 Recent hemorrhagic stroke Recent active bleeding
See a specialist
See a specialist
Mechanical valvular prosthesis OR rheumatic mitral stenosis2
See a specialist No data available
Active liver disease OR liver enzymes >2 to 3 X NUL3 Bariatric surgery (biliopancreatic)4 Morbid obesity with BMI 40 kg/m2 5 MAJOR interaction with a powerful CYP3A4 and/or P-gp inductor or inhibitor (See pages 9 to 11) Triple association with ASA and antiplatelet drugs (clopidogrel, prasugrel, or ticagrelor)6 Atypical venous thrombosis or thrombophilia7 Cancer7
Caution! See a specialist
Caution! See a specialist
Caution! See a specialist
Opt for LMWH
Key Drug of choice Drug of choice but use with caution Not recommended
Contraindicated Not evaluated for this population
Initiation of NOAC treatment is not recommended in patients presenting altered renal function with CrCL < 30 ml/min. For patients with a bioprosthesis valve or mitral valve repair, there is very little data on NOACs. Refer to a specialist. 3 NUL: Normal upper limit. 4 NOAC absorption is highly unpredictable in patients with a biliopancreatic diversion. Moreover, absorption of dabigatran may be reduced after a gastrectomy since it requires an acid environment for absorption. 5 There is very little data on patients presenting a BMI >_ 40 kg/m2. Refer to a specialist. 6 To prevent bleeding, it is important to limit the duration of triple therapy. 7 There is very little data on patients with thrombophilia or cancer. Refer to a specialist. 1
2
INFORMATION AND PHARMACOLOGY
07
PHARMACOKINETIC PARAMETERS
DABIGATRAN
RIVAROXABAN
APIXABAN
Peak effect
1-3 hrs
2-4 hrs
3-4 hrs
Half-life (T1/2)
12-17 hrs
5-9 hrs (Adults) 11-13 hrs (Seniors)
8-15 hrs
Excretion
Renal (85%)
Metabolized via CYP3A4 (66%) and the rest (33%) excreted unchanged by the kidneys3
A small amount metabolized via CYP3A4 (=25%), renal (27%) and fecal excretion
Metabolism
P-gp
CYP3A4
CYP3A4
Digestive tolerance
Dyspepsia 5-10%
n/a
n/a
1
1 2
Dabigatran requires an acid environment to be absorbed.
The half-life of dabigatran may be extended in the presence of altered renal function.
2
Renal excretion is dependent on Pâ&#x20AC;&#x201C;gp.
3
Note: Due to the short T 1/ 2 of NOACs, it is important to ensure good adherence to treatment and periodic review. - In the event of one or two missed doses of dabigatran, rivaroxaban DIE or apixaban, the missed dose should be taken as soon as possible, at least 6 hours before the next dose. NEVER double the dose to compensate for a missed dose. - When rivaroxaban is administered BID, the patient must take the missed dose as soon as possible so that the total daily dose = 30 mg. - If doses of a NOAC are missed for more than 48 hours, the treatment should be resumed immediately and the doctor notified so the situation can be re-evaluated (particularly for patients with a high risk of thromboembolism or who are waiting for electrical cardioversion).
08
INFORMATION AND PHARMACOLOGY
POTENTIAL INTERACTION MECHANISMS
Impact on CYP3A4: A drug may be a CYP3A4 substrate, inhibitor, or inductor. ALL NOACs are CYP3A4 substrates but their affinity varies depending on the molecule. Degree of affinity for CYP3A4: dabigatran < rivaroxaban = apixaban More another drug acts as an enzymatic inhibitor or inductor of CYP3A4, the stronger the interaction is with the NOAC and the impact on plasma concentrations. Impact on P-glycoprotein (P-gp): P-glycoprotein pumps drugs back into the intestinal lumen, which reduces their absorption and therefore their plasma concentrations. P-glycoprotein is also involved in tubular secretion of certain drugs, including rivaroxaban. Degree of affinity for P-gp: rivaroxaban = apixaban < dabigatran
INFORMATION AND PHARMACOLOGY
09
DRUG INTERACTIONS IMPACT ON PLASMA CONCENTRATIONS OF NOACS*
Amiodarone Antiacids1 Atorvastatin Digoxin Diltiazem
MECHANISM INVOLVED P-gp substrate minor GI absorption P-gp & CYP3A4 P-gp P-gp CYP3A4 weak
Dronedarone
P-gp & CYP3A4
Fluconazole
CYP3A4
Verapamil2
P-gp CYP3A4 weak
Clarithromycin Erythromycin Cyclosporin Tacrolimus Protease inhibitor (HIV treatment)3 Ketoconazole Itraconazole Voriconazole Posaconazole Rifampicin Carbamazepine Phenytoin Phenobarbital St. Johnâ&#x20AC;&#x2122;s Wort Grapefruit juice
P-gp & CYP3A4 P-gp P-gp CYP3A4 major inhibitor P-gp CYP3A4 major inhibitor
P-gp CYP3A4 minor inductor
CYP3A4 minor inhibitor
Dexlansoprazole, esomeprasole, lansoprazole, omeprazole, pantoprazole, rabeprazole, ranitidine, cimetidine, liquid antacids (e.g., MaaloxTM), etc.
1
Dabigatran should be taken 2 hrs before verapamil to avoid interaction.
2
Ritonavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, saquinavir, tipranavir, etc.
3
10
INFORMATION AND PHARMACOLOGY
DABIGATRAN 12-60%
RIVAROXABAN Minor effect
12-30%
No effect
18% No effect
No effect
No effect
Minor effect
70-100%
15-20%
No effect
40%
42%
Minor effect
30-54% 50%
Up to
66%
Minor effect
140-150%
No effect
No effect
12-180%
APIXABAN
153 %
Up to 150%
Up to
50%
CAUTION! Avoid combination
Strong
100%
54%
CAUTION! Avoid combination
* This table is not exhaustive. It is important to take into account the number of CYP3A4 substrates and the patient’s renal function to evaluate the actual clinical impact of the interaction.
Key : Use contraindicated. Avoid concurrent administration. : No data. INFORMATION AND PHARMACOLOGY
11
Management
DRUG ADMINISTRATION
DABIGATRAN * PradaxaTM - To be taken with or without food - Capsules should not be opened, broken, or chewed (Exposure increased by 75%) - Should not be administered through a nasogastric tube - Granules should not be sprinkled on food - Capsule sensitive to humidity. Keep in the original packaging at all times. Cannot be used in a conventional Dispill pack or dosette. RIVAROXABAN * 101010 XareltoTM
151515 202020
- 10 mg tablet: To be taken with or without food - 15 mg and 20 mg tablets: MUST be taken with food to enhance bioavailability - Bioavailability unchanged if ground and administered by nasogastric tube (NGT) - No data on administration by gastrostomy or jejunostomy APIXABAN * EliquisTM - To be taken with or without food - Bioavailability unchanged if ground and administered by NGT - No data on administration by gastrostomy or jejunostomy
Capsules and tablets are shown actual size.
*
14
MANAGEMENT
MONITORING NOAC-TREATED PATIENTS Frequency
Actions to Take
Adherence to treatment
Each visit
- Complete patient training if necessary. - Provide positive reinforcement. - Inform the patient of available aids (dosettes, Dispill, etc.). - Make sure that patients take their medication twice a day, if applicable.
Identification of anticoagulated patient
Each visit
- Make sure that patients’ medical records are up-to-date, with a complete list of their medications. - Encourage patients to wear a Medic-Alert bracelet or carry a card indicating that they are taking anticoagulant drugs. - Tell patients that they must always inform healthcare professionals (doctor, pharmacist, dentist, nurses) that they are taking anticoagulant drugs.
Each visit Occurrence of thromboembolism events
- Ask questions about symptoms suggesting a stroke or TIA, a DVT or PE.
Bleeding
Each visit
- Review indication, dose, or agent based on the clinical situation. - Check for proctorrhagia, melena, hematuria, gynecological bleeding, etc. - Update HAS-BLED score.
Adverse effects
Each visit
- Change agent, if necessary. - Consider warfarin if necessary.
Drug Interactions
Each visit
- Review patient’s complete list of drugs. - Take into account over-the-counter drugs (e.g., St. John’s Wort, anti-inflammatories, etc.).
Blood Tests
Baseline - Baseline levels: Hb, renal tests BEFORE and liver function. starting treatment - Check hemoglobin and renal Annually and liver function. for ALL NOAC-treated patients Every 6 months
- Check renal function if • CrCL 30–60 ml/min • Patient is on dabigatran • Patient’s age > 75
Every 3 months (minimum)
- Check renal function if • CrCL approx. 30 ml/min • Change in clinical status (e.g., decompensated heart failure) MANAGEMENT
15
APIXABAN
RIVAROXABAN
DABIGATRAN
SWITCHING FROM ONE AGENT TO ANOTHER
Heparine IV to NOAC
LMWH1 to NOAC
VKA to NOAC
Start NOAC once the heparin infusion is stopped.
Start NOAC at time scheduled for the next dose of LMWH.
Stop VKA and start dabigatran when INR < 2.0.
Start NOAC once the heparin infusion is stopped.
Start NOAC at time scheduled for the next dose of LMWH.
Stop VKA and start rivaroxaban when INR 2.5.
Start NOAC once the heparin infusion is stopped.
Start NOAC at time scheduled for the next dose of LMWH.
Stop VKA and start apixaban when INR < 2.0.
All the recommendations in this table apply to the use of a LMWH at the therapeutic dose. In the case of prophylactic doses of LMWH, ask a pharmacist to determine the best time to administer the drug. These recommendations are based on pharmacokinetic data on the molecules rather than on clinical evidence.
1
NOACs should never be stopped before starting a VKA. In such cases, evaluate the patient clinical condition to determine if the use of interim bridging parenteral anticoagulant (heparin IV or LMWH) is necessary until a therapeutic INR is reached.
2
16
MANAGEMENT
NOAC to Heparine IV or LMWH
NOAC to VKA2
CrCL > 30 ml/min: Start heparin IV or LMWH 12 hrs after last dose of dabigatran. CrCL < 30 ml/min: Start heparin IV or LMWH 24 hrs after last dose of dabigatran.
CrCL 50 ml/min: Start VKA 3 days before stopping dabigatran. CrCL 30-49 ml/min: Start VKA 2 days before stopping dabigatran.
Start heparin IV or LMWH at time scheduled for the next dose of rivaroxaban.
Continue rivaroxaban until INR 2.0, then stop.
Start heparin IV or LMWH at time scheduled for the next dose of apixaban.
Continue apixaban until INR 2.0, then stop.
A NOAC should NEVER be given at the same time as a LMWH or IV Heparin. All NOACs can increase the INR value. It is impossible to evaluate the anticoagulation status of a patient based on the INR value. Nevertheless, during the concomitant phase when switching from a NOAC to a VKA, it is recommended the INR be measured just before the next NOAC dose (trough). Once the NOAC is stopped, it is necessary to wait for the INR to reliably reflect the VKAâ&#x20AC;&#x2122;s effect. - 48 hrs after the last dose of dabigatran - 24 hrs after the last dose of rivaroxaban - 12 hrs after the last dose of apixaban
MANAGEMENT
17
NOAC MANAGEMENT BEFORE & AFTER SURGERY OR INVASIVE PROCEDURES
1 - BEFORE surgery: Evaluate risk of bleeding VERY LOW RISKâ&#x20AC;&#x2030;1
LOW RISK
-T ooth extraction (1 to 3 teeth), dental cleaning, periodontal surgery, lancing of an abscess, installation of a dental implant -S kin biopsy, lancing of an abscess, minor dermatological surgery -C ataract or glaucoma surgery -E ndoscopy WITHOUT biopsy
- Laparoscopy - Cholecystectomy - Dental procedure - Dermatological procedure - Ophthalmic procedure - Coronary angiogram - Gastroscopy/colonoscopy WITHOUT polypectomy - Bone marrow biopsy - Implantation of a pacemaker or defibrillator - Angiogram - Catheter ablation2
18
MANAGEMENT
INTERMEDIATE RISK
HIGH RISK
- Any other intra-abdominal, intrathoracic, orthopedic, or vascular surgery - Endoscopy WITH biopsy
- Neurological surgery - Epidural anesthesia - Spinal tap - Cardiac surgery (CABG, valve replacement) - Major vascular surgery (abdominal aortic aneurysm) - Major urological surgery (prostatectomy, bladder tumor resection) - Thoracic surgery (pneumonectomy) - Orthopedic surgery (THR, TKR) - Abdominal/intestinal surgery - Invasive procedures: Bladder/prostate/liver/kidney biopsy, polypectomy, etc.
In general, it is not necessary to stop NOACs before surgery involving a VERY low risk of bleeding. It is sufficient to omit the morning dose or perform the procedure just prior to the next dose (trough).
1
Although an ablation of atrial flutter or fibrillation is considered to involve a low risk of bleeding, cessation of the anticoagulant before the procedure is not recommended because of the risk of stroke in these patients.
2
Note: This list is not exhaustive and the clinical context of each patient must be taken into account. It is recommended that the risk of bleeding be assessed by the specialist who will perform the procedure.
MANAGEMENT
19
NOAC MANAGEMENT BEFORE & AFTER SURGERY - (CONT.)
2 - BEFORE surgery: Estimate when to stop drug treatment DABIGATRAN LOW risk of bleeding
INTERMEDIATE or HIGH risk of bleeding
Stop 1–2 days BEFORE
Stop 2–3 days BEFORE
- If CrCL 30–50 ml/min: Stop one day more - If CrCL < 30 ml/min: Stop two days more
RIVAROXABAN / APIXABAN LOW risk of bleeding
INTERMEDIATE or HIGH risk of bleeding
Stop 1–2 days BEFORE
Stop 2–3 days BEFORE
3-A FTER surgery: Resume NOAC based on the risk of bleeding. - Interventions involving a LOW risk of bleeding: Wait 24 hrs before resuming NOAC. – Interventions involving an INTERMEDIATE or HIGH risk of bleeding: Wait 48 to 72 h rs before resuming NOAC. Note: This information is based SOLELY on pharmacokinetic data on the NOACs. A specialist MUST evaluate the risk of bleeding AND thromboembolism as well as whether hemostasis has been achieved.
20
MANAGEMENT
MANAGEMENT OF BLEEDING
MINOR BLEEDING
+ Check time last dose was taken and estimate time to reach hemostasis - CrCL 50-80ml/ min: 24-36 hrs - CrCL 30-50ml/ min: 36-48 hrs - CrCL < 30 ml/ min: 48 hrs Evaluate concomitant medication, including aspirin and antiplatelet drugs Consider oral administration of activated charcoal in the case of a NOAC OVERDOSE if the latter has been ingested in the previous 2 hours.
LIFE-THREATENING BLEEDING
MAJOR BLEEDING
+ Support measures - Mechanical compression -F luid repletion (to avoid acute renal failure and drug accumulation) -B lood transfusion PRN -C onsider: Platelet concentrate if antiplatelet drugs are taken -C onsider: Fresh frozen plasma if associated coagulopathy For DABIGATRAN - Consider dialysis - Charcoal hemoperfusion may also be considered
Consider administering unactivated prothrombin complex concentrate (PCC) on the recommendation of an hematologist (possible risk of thromboembolism)* Example: BeriplexTM 50 units/kg Max: 5,000 units
* There is no clinical data on the efficacy of unactivated PCCs. To be used ONLY in cases of life-threatening bleeding following a risk/benefit analysis.
Note: Vitamin K, plasma, and DDAVP TM cannot be used to stop bleeding caused by a NOAC. Although CyklokapronTM can be used as adjunctive therapy in the event of mucocutaneous bleeding, it cannot reverse the effect of a NOAC.
MANAGEMENT
21
MEASURING ANTICOAGULANT EFFECT
No special monitoring is recommended for dose adjustment. Monitoring may be advisable in certain clinical situations (bleeding, perioperative period, noncompliance, etc.). Quantitative tests to measure NOAC concentrations are not currently available.
DABIGATRAN
RIVAROXABAN
APIXABAN
2 hrs after ingestion
1 to 4 hrs after ingestion
1 to 4 hrs after ingestion
12 to 24 hrs after ingestion
16 to 24 hrs after ingestion
16 to 24 hrs after ingestion
Prothrombin time in INR units
Not useful
Not useful
Not useful
Prothrombin time in sec.1
Of little use
Extension varies with reactant
Extension varies with reactant 5
Activated cephalin time (APTT or ACT)
Extends to about 2 X normal value at peak activity 2
Extension varies with reactant
Extension varies with reactant
Thrombin time
Too sensitive 3
Of little use
Of little use
Anti–Xa tests
Not useful
Useful if specially calibrated 4
Useful if specially calibrated 4
Plasma peak Plasma trough
ata rarely available in laboratories. D The degree of extension varies depending on the reactant, making it impossible to predict the concentration. 3 The concentration cannot be predicted based on the degree of extension. If the test is normal, the residual amount of dabigatran is negligible. 4 Special calibration (different than that for LMWH) is required for monitoring anti–Xa NOACs. This is not currently available. 5 Apixaban has less impact on prothrombin time than rivaroxaban. 1
2
22
MANAGEMENT
2014 CCS RECOMMENDATIONS
AGE > 65
YES
NOAC > WARFARIN
YES
NOAC > WARFARIN
YES
ASA
NO
STROKE OR TIA IN THE PAST OR HIGH BLOOD PRESSURE OR CARDIAC FAILURE OR DIABETES NO
ATHEROSCLEROSIS DISEASE OR ARTERIAL VASCULAR DISEASE NO
NO ANTITHROMBOTICS
Before starting an anticoagulant treatment, always consider and modify risk factors for bleeding (high blood pressure, antiplatelet drugs, NSAIDs, and alcohol consumption), including those that are specific to NOACs (altered renal function, age > _ 75 and low weight).
CHADS2 score: Embolism Risk Assessment Scale C H A D S
Cardiac failure High blood pressure Age 75 Diabetes Stroke or TIA in the past
1 point 1 point 1 point 1 point 2 points
HAS-BLED score: Assessing Risk of Embolism H A S B L E D
High blood pressure Altered renal or hepatic function Stroke Bleeding Labile INR Age > 65 Interactions or alcohol consumption
1 point 1 or 2 points 1 point 1 point 1 point 1 point 1 or 2 points MANAGEMENT
23
COMPARISON OF CHADS2 AND HAS–BLED SCORES
CHADS2 Score
Risk of Stroke (%/Yr.)
HAS–BLED Score
Risk of Bleeding (%/Yr.)
0
1.9
0
1.1
1
2.8
1
1.0
2
4.0
2
1.9
3
5.9
3
3.7
4
8.5
4
8.7
5
12.5
5
12.5
6
18.2
6-9
> 12.5
Document produced by Isabelle Taillon, Pharmacist, IUCPQ, in collaboration with the following professionals. Collaborators Dr. Patrick Béliveau, Cardiologist, HDQ Jean Bournival, Pharmacist, HDL François Brouillette, Pharmacist, HSFA Dr. Isabelle Bureau, Internist, HDL Dr. Jean Champagne, Cardiologist/Electrophysiologist, IUCPQ Lyne Charbonneau, Clinical Nurse, IUCPQ Dr. Christine Demers, Hematologist, HEJ Dr. Jean–Pierre Déry, Cardiologist and Hemodynamics Specialist, IUCPQ Dr. Valérie Gaudreault, Cardiologist, HDQ Dr. Philippe Gilbert, Cardiologist, HEJ With unrestricted funding from Bayer Inc.
24
MANAGEMENT
Dr. Isabelle Labonté, Internist, IUCPQ Dr. Ariane Mackey, Neurologist, HEJ Louis–Etienne Marchand, Pharmacist, HDL Dr. Isabelle Nault, Cardiologist/Electrophysiologist, IUCPQ Dr. Clarence Pelletier, Pulmonologist, HDL Sébastien Perreault, Pharmacist, CHUL Dr. François Philippon, Cardiologist/Electrophysiologist, IUCPQ Dr. Michel Samson, Cardiologist, CHUL Dr. Steve Verreault, Neurologist, HEJ Dr. Pierre Voisine, Cardiac Surgeon, IUCPQ
References - C onnolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation (RELY Study). NEJM 2009; 361:1139–51. - G ranger CB, Alexander JH, McMurray JJV. Apixaban versus Warfarin in Patients with Atrial Fibrillation (ARISTOTLE Study). NEJM 2011; 365 (11): 981–92. - Heidbuchel H, Verhamme P, Alings M et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non–valvular atrial fibrillation. Europace 2013; 15: 625–51. - January CT, Wann LS, Alpert JS et al. 2014 AHA/ACC/HRS Guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology / American Heart Association task force on practice guidelines and the Heart Rhythm Society. Circulation 2014. Epub ahead of print. - Institut National d’Excellence en Santé et en Service Sociaux (INESSS). Anticoagulothérapie chez l’adulte: fibrillation auriculaire. Updated March 2014. - A pixaban monograph (EliquisTM) November 2014. - Dabigatran monograph (PradaxaTM) June 2014. - Rivaroxaban monograph (XareltoTM) July 2014. - Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation (ROCKET Study). NEJM 2011; 365:883–891. - Verma A, Cairns JA, Mitchell B et al. 2014 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation. Can J Cardiol 2014. Epub ahead of print.
Limitations of Use: The Guide to the Use of New Oral Anticoagulants can be a practical tool for healthcare professionals. However, its use may need to be adapted based on the professional’s clinical judgment and the healthcare setting. The Guide to the Use of New Oral Anticoagulants in no way replaces the manufacturer’s indications or instructions or professional best practices. Despite the care taken and efforts made to ensure that the information in this guide was accurate at the time of publication, the collaborative team that produced this guide does not guarantee its timeliness or exhaustive nature. Therefore, the user must take into account the publication date and the fact that the information may be outdated. Copyright: The Guide to the Use of New Oral Anticoagulants was produced by Isabelle Taillon, Pharmacist, in collaboration with a number of healthcare professionals at university institutions in the Québec City area. Any reproduction, adaptation, modification or translation, in any way whatsoever of this guide, in whole or in part, is subject to the prior written approval of Isabelle Taillon.
Version 1 - May 15 2015