Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3865_Библиотеки_им_академика_М_И_Перельмана
.pdf
150 Anticoagulation Therapy
https://t.me/med1917
TABLE 7-9: (Continued)
Patient Factor Consideration Recommended Oral Agent
Renal
dysfunction
Hepatic
dysfunction
Older age • Age ≥75 years old Apixaban, rivaroxaban,
Extremes of
40, 41
weight
Stability on
warfarin
Adherence to
medication
Difficulty
adhering to
frequent clinic
monitoring
Willingness to
pay
Patient
preferences
CrCl: creatinine clearance, DAPT: dual antiplatelet therapy, DOAC: direct-acting oral
anticoagulant, kg: kilograms
•
CrCl <30 mL/min Warfarin
CrCl 30–50 mL/min Dose adjustment required for
•
• CrCl ≥50 mL/min Any oral agent
• CrCl >95 mL/min Any oral agent, except
•
Child Pugh A Any oral agent
• Child Pugh B Warfarin, dabigatran
• Child Pugh C Warfarin
• Age <75 years old Any oral agent
• Weight <50 kg or >120 kg Warfarin
• Time in therapeutic range ≥66% Warfarin
• Time in therapeutic range <66%
(despite good adherence)
• Once daily dosing preferred Warfarin, rivaroxaban, edoxaban
• Difficulty with adherence—would
benefit from measurable monitoring
and close follow up
• Poor warfarin adherence Warfarin, aspirin; DAPT;
• Physical barriers
• Rural location
• Lack of transportation
•
Investigate insurance coverage,
including amount of co-payment
Identify any required insurance
•
coverage criteria (prior
authorization, etc.)
• Identify eligibility for manufacturersponsored programs (usually
requires income statements)
• Weigh options discussing patient
values and preferences
rivaroxaban in atrial fibrillation
avoid edoxaban in atrial
fibrillation
edoxaban, warfarin
DOAC
Warfarin
likely poor DOAC candidate
Dabigatran, rivaroxaban,
apixaban, edoxaban
Shared decision making with
patient/caregivers
Verify access to therapy at time
of prescribing
Warfarin: potentially lower drug
cost and fewer drug access
issues
Shared decision making with
patient/caregivers
DIRECT ORAL ANTICOAGULANTS 151
https://t.me/med1917
• In clinical trials for treatment of acute venous
thromboembolism, dabigatran and edoxaban
were studied with 5–10 day parenteral pretreatment lead-in.
11,12
It is important to note that
this was not overlapping therapy. The patients
in the DOAC arms were switched to dabigatran
or edoxaban after the initial parenteral
anticoagulant was stopped. Rivaroxaban and
apixaban were studied without a parenteral
pre-treatment, thus providing an advantage
of convenience over other agents.
13-16
Patients
wishing to avoid the cost and inconvenience of
injections may opt for rivaroxaban or apixaban.
• All DOACs carry a black box warning against use
in patients with a mechanical heart valves. The
RE-ALIGN trial found that the use of dabigatran
in patients with mechanical heart valves was
associated with higher rates of thrombosis and
bleeding complications.
37
• In non-valvular atrial fibrillation (NVAF) trials,
both dabigatran and rivaroxaban increased the
risk for gastrointestinal (GI) bleeding compared
to warfarin.
7,8
Clinicians may consider avoiding
these agents in patients with a history of GI
bleeding. In addition, dabigatran has a high
rate of dyspepsia, and patients should be
routinely asked about side effects to avoid selfdiscontinuation.
• Patients taking a DOAC plus any combination
of dual antiplatelet therapy (ASA+clopidogrel/
ticagrelor/prasugrel) or higher dose ASA (i.e., >81
mg/daily) were generally excluded from DOAC
clinical trials and have not been extensively
studied. Antiplatelets combined with any type of
anticoagulant will increase bleeding risk. With
warfarin, the INR can be titrated to the lower
end of the goal range in an attempt to minimize
bleeding complications. Emerging evidence and
ongoing trials may provide needed guidance as to
optimal antithrombotic combinations (Table 7-3:
PIONEER PCI, AUGUSTUS, RE-DUAL PCI).
152 Anticoagulation Therapy
https://t.me/med1917
• In those aged ≥75 years, GI bleeding and major
bleeding risk is higher with dabigatran compared
with warfarin.
Beers Criteria for potentially inappropriate
medication use in older patients because safer
alternatives exist.
• Patients with extremes in body weight (<50 kg or
>120 kg) make up a small proportion of patients
in the DOAC clinical trials. Due to limited data,
it may be safest to use warfarin until more data in
these patients are available.
A meta-analysis of the DOAC trials for atrial
•
fibrillation found a greater relative reduction
in major bleeding with DOACs when the time
in therapeutic range (TTR) was <66% than
when it was 66% or more. Therefore, patients
well-managed (TTR ≥66%) on warfarin may
not derive advantages for bleeding or efficacy if
switched to a DOAC.
of DOACs may increase patient and clinician
satisfaction in appropriately selected patients.
38
Dabigatran is included on the
39
40, 41
42
However, the convenience
• Manufacturer sponsored co-pay coupon
cards cannot be used by a patient that has
government-sponsored insurance
(i.e., Medicare, Medicaid, or Tricare).
DOACs are given in fixed doses, but may warrant adjustments for certain
clinical characteristics such as renal function, body weight, or concomitant
drug therapies. Adjustments vary by DOAC, by indication and even by
country. Therefore, clinicians are encouraged to refer to labeled guidance
and to work closely with clinical pharmacists to ensure appropriate dosing
(see Table 7-10).
DIRECT ORAL ANTICOAGULANTS 153
https://t.me/med1917
DOAC DOSING BY U.S. INDICATION
TABLE 7-10: Dosing of DOACs
Drug U.S. Labeled Indication U.S. Labeled Dosing
Dabigatran
1
Hip arthroplasty CrCl >30 mL/min: 110 mg daily on first day,
then 220 mg daily
CrCl ≤30 mL/min or on dialysis: Avoid use
CrCl <50 mL/min with concomitant use of
strong P-gp inhibitors: Avoid use
VTE treatment
Initiation of therapy: After 5–10 days of
parenteral pre-treatment
CrCl >30 mL/min: 150 mg BID
#
Rivaroxaban
Reduction of VTE recurrence
CrCl >30 mL/min: 150 mg BID
CrCl ≤30 mL/min or on dialysis: Avoid use
CrCl <50 mL/min with concomitant use of
strong P-gp inhibitors: Avoid use
Non-valvular atrial fibrillation CrCl >30 mL/min: 150 mg BID
CrCl 15–30 mL/min: 75 mg BID*
CrCl <15 mL/min or on dialysis: Avoid use
CrCl 30−50 mL/min with concomitant use of
strong P-gp inhibitors: 75 mg BID
CrCl <30 mL/min with concomitant use of
strong P-gp inhibitors: Avoid use
2
Hip arthroplasty
CrCl ≥30 mL/min: 10 mg daily with or without
food x 35 days
Knee arthroplasty
CrCl ≥30 mL/min: 10 mg daily with or without
food x 12 days
CrCl <30 mL/min or on dialysis: Avoid use
Concomitant use of strong dual inhibitors of
P-gp and CYP3A4: Avoid use
VTE treatment
CrCl ≥30 mL/min: 15 mg BID with food
x 21 days; then 20 mg daily with food
Reduction of VTE recurrence
CrCl ≥30 mL/min: 20 mg daily with food, or 10
mg daily after at least 6 months of standard
anticoagulant treatment
CrCl <30 mL/min or on dialysis: Avoid use
Concomitant use of strong dual inhibitors of
P-gp and CYP3A4: Avoid use
Non-valvular atrial fibrillation CrCl >50 mL/min: 20 mg daily with food
CrCl 15–50 mL/min: 15 mg daily with food*
CrCl <15 mL/min or on dialysis: Avoid use
Concomitant use of strong dual inhibitors of
P-gp and CYP3A4: Avoid use
#
#
#
#
#
(continued)
154 Anticoagulation Therapy
https://t.me/med1917
TABLE 7-10: (Continued)
Drug U.S. Labeled Indication U.S. Labeled Dosing
3
Apixaban
Hip arthroplasty
2.5 mg BID x 35 days
Edoxaban
Knee arthroplasty
2.5 mg BID x 12 days
Concomitant use of strong dual inhibitors of
P-gp and CYP3A4: Avoid use
VTE treatment
Reduction of VTE recurrence
10 mg BID x 7 days; then 5 mg BID
2.5 mg BID (after 6 months of treatment)
Concomitant use of strong dual inhibitors of
P-gp and CYP3A4: Reduce dose by 50% if
taking 10 mg or 5 mg dose.** Avoid use if
taking 2.5 mg dose.
Non-valvular atrial fibrillation 5 mg BID
2.5 mg BID (if ≥2 of the following: age ≥80
years, weight ≤60 kg, SCr ≥1.5 mg/dL)
Concomitant use of strong dual inhibitors of
P-gp and CYP3A4: Reduce dose by 50% if
taking 5 mg dose.** Avoid use if already taking
2.5 mg dose.
ESRD on dialysis
#¥
5 mg BID
2.5 mg BID (if age ≥80 year and/or weight ≤60 kg)
Concomitant use of strong dual inhibitors of
P-gp and CYP3A4: Reduce dose by 50% if
taking 5 mg dose.** Avoid use if taking 2.5 mg
dose.
4
Non-valvular atrial fibrillation CrCl >95 mL/min: Use is not recommended
CrCl 51–95 mL/min: 60 mg daily
CrCl 15–50 mL/min: 30 mg daily*
CrCl <15 mL/min or on dialysis: Avoid use
Concomitant use of strong P-gp inhibitors: No
dose adjustment necessary.
#
VTE treatment Initiation of therapy after 5–10 days of
*Patients with CrCl <30 mL/min not studied. Dosing for CrCl down to 15 L/min based on
pharmacokinetic modeling.
**Not studied in safety and efficacy trials. Based on pharmacokinetic data only.
#Not recommended. See more detailed information in Clinical Pearls below.
¥FDA-labeled dosing recommendations for ESRD only pertain to non-valvular atrial fibrillation.
The manufacturer does not provide ESRD dosing adjustment recommendations for VTE.
CrCl: creatinine clearance, BID: twice daily, CYP-3A4: cytochrome P450 3A4, ESRD: end stage
renal disease, kg: kilograms, mg: milligrams, mL: milliliters, min: minutes, P-gp: permeabilityglycoprotein, SCr: serum creatinine, x: times
parenteral pre-treatment
CrCl ≥51 mL/min: 60 mg daily
CrCl 15–50 mL/min or weight <60 kg or use of
Specific P-gp inhibitor: 30 mg daily*
CrCl <15 mL/min or on dialysis: Avoid use
#
DIRECT ORAL ANTICOAGULANTS 155
https://t.me/med1917
• In the large Phase III trials of DOACs, renal
function was estimated using the CockcroftGault equation and actual body weight.
Clinicians should consider using the same
approach in clinical practice when dose adjusting
(or avoiding) DOACs in patients with renal
impairment.
• Although apixaban has a labeled indication
for use in NVAF with end-stage renal disease
(ESRD) on hemodialysis, use in this population
is not recommended. This labeling is based on
a single-dose study that did not account for
accumulation in a very small population (n=8
patients).
43
Rivaroxaban also has a suggestion
in their labeling that it may be a viable option
in NVAF patients on dialysis, based on a similar
study (n=8, single dose).
44
Until more safety data
are available for repeat dosing of DOACs in this
population, use should be avoided in severe renal
impairment.
• A post-hoc subgroup analysis suggests patients
enrolled in the ENGAGE-AF TIMI 48 with
a creatinine clearance > 95 mL/min may
experience decreased efficacy with edoxaban
for the prevention of ischemic stroke compared
with warfarin. Therefore, the FDA labeling
recommends against use of edoxaban in patients
with atrial fibrillation and creatinine clearance
greater than 95 mL/min.
4
• It is important for clinicians to perform DOAC
dose adjustments when needed. However, empiric
dose adjustments that are not based on studied
criteria should be avoided, as this may lead
to suboptimal therapy and increased adverse
45-47
events.
PERI-PROCEDURAL MANAGEMENT OF
DOACS
Refer to Chapter 10 for detailed information on peri-procedural management of the DOACs.
156 Anticoagulation Therapy
https://t.me/med1917
TRANSITIONING BETWEEN
ANTICOAGULANTS
Refer to Chapter 10 for detailed information on transitioning between
anticoagulants.
MANAGEMENT OF DOAC-ASSOCIATED
CLINICALLY RELEVANT BLEEDING
Refer to Chapters 8 and 9 for detailed information regarding management
of clinically relevant DOAC-associated bleeding.
TRANSITIONS OF CARE
Compelling evidence shows that inadequate care transitions are associated
with suboptimal patient outcomes and a negative financial impact on the
healthcare system. Therefore, national care transitions quality initiatives
have become a major focus for numerous regulatory bodies, including The
Joint Commission.48 High-risk medications, such as anticoagulants, require
vigilance, particularly during care transitions. A systematic approach to
transitions of care is especially critical for DOACs, given the number of
clinical nuances in their use. The DOACs carry indication-specific dosing
recommendations and require dose de-escalations, switches, or adjustments
for a variety of reasons and may require temporary interruption for invasive
procedures. Furthermore, cost and patient access to DOAC therapy are
important transitions of care issues to navigate. Use of a DOAC discharge
checklist (see Table 7-11) is strongly recommended, as it will help to ensure
all key aspects of patient care with DOAC therapy are addressed.
PATIENT COUNSELING PEARLS FOR
OPTIMAL DOAC USE
Tables 7-12 and 7-13 offer key patient counseling points that should aid
clinicians in empowering patients and caregivers and, consequently, promote
the safe and effective use of DOACs.
DIRECT ORAL ANTICOAGULANTS 157
https://t.me/med1917
TABLE 7-11: DOAC Discharge Checklist
39,49
• Patient is a good DOAC candidate.
•
Assess patient’s eligibility for outpatient treatment.
•
Confirm consistent patient access to DOAC for duration of therapy.
•
If transitioning to another inpatient care setting (e.g., skilled nursing facility), ensure DOAC
is on formulary.
DOAC recognized as an oral anticoagulant by patient, caregivers, and providers.
•
•
Provision of thorough DOAC education to patient and/or caregiver in their preferred
language and at an appropriate literacy level.
Safety net phone number provided to patient/caregiver (who to call with questions).
•
•
Referral or handoff to appropriate provider (anticoagulation clinic, primary care physician,
etc.).
Time of last drug administration in current setting and time of next scheduled dose in new
•
setting.
For VTE patients: Prescribed strategy for appropriate dose change after initial therapy
•
(either switch to DOAC or DOAC dose de-escalation).
•
Consolidated documentation and communication of key anticoagulation information to
next care setting including:
Indication for anticoagulation
Intended duration of therapy
DOAC dose and scheduled time of administration
Contact information for anticoagulation provider
Follow-up arranged for periodic (every 3–12 months) assessment of the following:
•
Satisfaction with and tolerance of DOAC therapy
Renal and liver function
Upcoming invasive procedures
New drug interactions or contraindications
Possibility of stopping anticoagulation therapy
TABLE 7-12: General Counseling Points for All DOAC Agents
• Inform provider of all medication changes, including over-the-counter and herbals.
• Avoid taking non-steroidal anti-inflammatory drugs (NSAIDs) while taking anticoagulation
therapy.
• Avoid taking aspirin before discussing its use with provider.
• Carry ‘‘anticoagulant ID wallet card’’ or wear “MedicAlert” bracelet/necklace to alert
emergency medical responders.
DO NOT stop taking DOAC without a physician order and get prescriptions refilled on
•
time.
• Communicate any difficulty accessing refills BEFORE running out of medication.
• Report signs and symptoms of bleeding and/or clotting.
• Inform all healthcare providers before invasive procedures or surgery, including dental.
• Inform healthcare provider if pregnant or plan to become pregnant.
• Inform healthcare provider if breastfeeding.
• Notify anticoagulation provider of any hospitalization or emergency department visits.
• Anticoagulation monitoring and follow up are necessary despite no routine coagulation
testing.
39,48
158 Anticoagulation Therapy
https://t.me/med1917
TABLE 7-13: DOAC-Specific Patient Counseling Points
Dabigatran Rivaroxaban Apixaban Edoxaban
Dosing BID Daily BID Daily
Missed dose Take as soon as
possible on the
same day but at
least 6 hr before
next scheduled
dose
Food Full glass of water
±food
Storage MUST store in
original container,
keep sealed, use
within 120 days
Crushing Swallow whole;
do not crush, cut,
or open.
If taking 15 mg
twice daily for VTE
induction and 1
dose is missed,
can take 30 mg 1x
to make up
All other doses:
Take as soon as
possible same day
15 mg and 20 mg:
Take with food
10 mg ±food
Ambient
conditions, can
place in pill box
Can crush, mix
with food. May
give via NG tube.
Take as soon
as possible
same day and
continue BID
administration
±food ±food
Ambient
conditions, can
place in pill box
Can crush,
suspend in D5W,
and give via NG
tube.
Take as soon as
possible same
day
Ambient
conditions, can
place in pill box
Can crush, mix
with food. May
give via NG
tube.
1-4
BID: twice daily, hr: hours; mg: milligrams, NG: nasogastric, VTE: venous thromboembolism
DIRECT ORAL ANTICOAGULANTS 159
https://t.me/med1917
REFERENCES AND KEY ARTICLES*
1. Dabigatran package insert [Internet]. Available from: http://docs.boehringer-ingelheim.
com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. Accessed March 14, 2017.
2. Rivaroxaban package insert [Internet]. Available from: https://www.xareltohcp.com/
shared/product/xarelto/prescribing-information.pdf. Accessed March 14, 2017.
3. Apixaban package insert [Internet]. Available from: https://packageinserts.bms.com/pi/
pi_eliquis.pdf. Accessed March 14, 2017.
4. Edoxaban package insert [Internet]. Available from: http://dsi.com/prescribinginformation-portlet/getPIContent?productName=Savaysa&inline=true. Accessed
March 14, 2017.
5.
European Medicines Agency - Find medicine - Xarelto [Internet]. Available
from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/
medicines/000944/human_med_001155.jsp&mid=WC0b01ac058001d124. Accessed
March 14, 2017.
6. 20110719_322_E.pdf [Internet]. Available from: http://org.daiichisankyo.com/
media_investors/media_relations/press_releases/detail/005784/20110719_322_E.pdf.
Accessed March 14, 2017.
Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with
7.
atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151.
8. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular
atrial fibrillation. N Engl J Med. 2011;365(10):883-891.
9. Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients
with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
10. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with
atrial fibrillation. N Engl J Med. 2013;369(22):2093-2104.
11. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous
thromboembolism with dabigatran or warfarin and pooled analysis. Circulation.
2014;129(7):764-772.
12.
Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or
placebo in venous thromboembolism. N Engl J Med. 2013;368(8):709-718.
13. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, et al.
Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med.
2010;363(26):2499-2510.
14. EINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, et al. Oral
rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med.
2012;366(14):1287-1297.
15. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous
thromboembolism. N Engl J Med. 2013;369(9):799-808.
16. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous
thromboembolism. N Engl J Med. 2013;368(8):699-708.
17. Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso Ma, et al. Edoxaban versus
warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med.
2013;369(15):1406-1415.
Соседние файлы в папке Библиотека им академика М.И. Перельмана