IN THIS ISSUE
Antithrombotic Drugs........................................................p 61
Treatment Guidelines
from The Medical Letter
Published by The Medical Letter, Inc. 145 Huguenot Street, New Rochelle, NY 10801 A Nonprofit Publication
Volume 9 (Issue 110) October 2011
www.medicalletter.org
Updated March 2012
Tables
1. Drugs
2. Drugs
3. Drugs
4. Drugs
of Choice
for Acute Coronary Syndrome
for Venous Thromboembolism
for Atrial Fibrillation
Page 61
Pages 62-63
Page 64
Page 65
Antithrombotic Drugs
Arterial thrombi are composed mainly of platelet
aggregates held together by small amounts of fibrin.
Antiplatelet drugs are the drugs of choice for prevention
and treatment of arterial thrombosis, but anticoagulants
are also effective, and their effects can add to those of
antiplatelet drugs. Venous thrombi are composed
mainly of fibrin and trapped red blood cells, with relatively few platelets. Anticoagulants are the agents of
choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic
events in patients with atrial fibrillation.
Aspirin
None1
Aspirin2
Aspirin + dipyridamole;
or clopidogrel
UA/NSTEMI
Aspirin
+ clopidogrel or prasugrel or
ticagrelor
+ UFH or LMWH or
fondaparinux3
+ GPIIb/IIIa inhibitor
Acute MI (STEMI)
Aspirin
+ clopidogrel or prasugrel
or ticagrelor
+ UFH or LMWH or
fondaparinux3
+ GPIIb/IIIa inhibitor
PCI
Aspirin
+ clopidogrel or prasugrel
or ticagrelor
+ UFH or LMWH or bivalirudin
+ GPIIb/IIIa inhibitor
VTE Treatment
ANTIPLATELET DRUGS
Antiplatelet drugs are used mainly for primary and
secondary prevention and treatment of acute coronary
syndrome (ACS), which includes unstable angina/nonST-elevation myocardial infarction (UA/NSTEMI),
ST-elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI).
Drugs
VTE Prevention
Hospitalized Medical Patients
General Surgery
Orthopedic Surgery
Atrial Fibrillation
Peripheral Arterial Disease
Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines.
61
Antithrombotic Drugs
Table 2. Drugs for Acute Coronary Syndrome
Usual
Dosage
Renal
Dosing
Reversibility of
Antithrombotic Effect1
Aspirin generic
75-81 mg PO daily
No dosage adjustment
required; do not use if
CrCl <10 mL/min
Irreversible, 50-100%
dialyzable
75-100 mg PO qid
No dosage adjustment
required
Irreversible
No dosage adjustment
required; do not use if
CrCl <10 mL/min
Irreversible
No dosage adjustment
required
Irreversible
60 mg PO loading dose,
10 mg PO once daily4
No dosage adjustment
required
No dosage adjustment
required
Reversible5
Ticlopidine generic
250 mg PO bid
No dosage adjustment
required
Irreversible
Abciximab ReoPro
(Centocor/Lilly)
No dosage adjustment
required
Not known
Irreversible, dialyzable
Irreversible, dialyzable
No dosage adjustment
required
Drug
Antiplatelet Drugs
GPIIb/IIIa Inhibitors
62
per day) was more effective than aspirin alone in preventing a composite of vascular death, stroke, MI or
major bleeding (173 vs. 216 events). However, more
patients discontinued the combination (470 vs. 184),
mainly because of headache.4 The combination was
not more effective than clopidogrel alone in preventing
recurrent stroke.5
THIENOPYRIDINES The thienopyridines ticlopidine (seldom used now because of its toxicity),
clopidogrel (Plavix) and prasugrel (Effient) irre-
Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011
Antithrombotic Drugs
Table 2. Drugs for Acute Coronary Syndrome (continued)
Usual
Dosage
Drug
Renal
Dosing
Reversibility of
Antithrombotic Effect1
Protamine
(~60% neutralized)
Protamine
(~60% neutralized)
No antidote, dialyzable
No antidote, dialyzable
No dosage adjustment
required15
Vitamin K
Low-Molecular-Weight Heparins
Enoxaparin generic
UA/NSTEMI: 1 mg/kg SC q12h
Lovenox (Sanofi Aventis)
STEMI: 30 mg IV bolus plus
1 mg/kg SC, then 1 mg/kg
SC q12h9,10
Warfarin generic
2-10 mg PO daily14
Coumadin (Bristol Myers Squibb)
9. Dose for patients <75 years-old. For patients >75 years-old, 0.75 mg/kg SC q12h.
10. For PCI, no additional dosing is needed if the last SC administration was <8 hrs before balloon inflation. If >8 hrs, an IV bolus of 0.3 mg/kg should be given.
11. Dose for patients <75 years-old. For patients >75 years-old, 1 mg/kg SC once daily
12. Oasis 6 Trial Group. JAMA 2006; 295:1519.
13. For STEMI, initial dose is given IV.
14. Monitor daily and adjust dose until results in therapeutic range (INR 2-3) for >24 hrs. Dose will vary based on INR.
15. Patients with renal failure may have an increased risk of bleeding.
TICAGRELOR Ticagrelor (Brilinta) binds reversibly to the same P2Y12 receptor as the thienopyridines.
In one study (PLATO), ticagrelor plus aspirin was
more effective than clopidogrel plus aspirin in preventing cardiovascular death, with no increase in overall major bleeding. Ticagrelor was, however, associated with an increase in non-CABG-related bleeding and
a trend toward a higher risk of hemorrhagic stroke.10 A
subgroup analysis of the PLATO results showed that
ticagrelor was not superior to clopidogrel in the subset
of patients in North America, possibly due to use of
higher doses of aspirin in the US. The US labeling of
the drug, therefore, includes a boxed warning against
using >100 mg of aspirin per day.11
GLYCOPROTEIN IIb/IIIa (GPIIb/IIIa) RECEPTOR ANTAGONISTS The GPIIb/IIIa receptor
antagonists, which are administered intravenously, prevent platelet aggregation by competing with fibrinogen
and von Willebrand factor for platelet receptors.
Abciximab (ReoPro) is the Fab fragment of a chimeric
monoclonal antibody to the GPIIb/IIIa receptor that
binds to both activated and non-activated platelets.
While the plasma half-life of abciximab is only 30 minutes, its strong affinity for platelets results in measurable platelet inhibition for 24-48 hours, with low levels
still detectable after 15 days. Eptifibatide (Integrilin)
and tirofiban (Aggrastat) bind reversibly to the
GPIIb/IIIa receptor of activated platelets. Bleeding at
Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011
63
Antithrombotic Drugs
Table 3. Drugs for Venous Thromboembolism
Drug
Anticoagulants
Unfractionated Heparin
Low-Molecular-Weight Heparins
1 mg/kg SC bid or 1.5 mg/kg once daily
Enoxaparin3
100 IU/kg SC bid4 or
Dalteparin3
200 IU/kg once daily5
3
Tinzaparin
175 IU/kg SC once daily
Vitamin K Antagonist
Warfarin
Direct Thrombin Inhibitors
Dabigatran3
Desirudin3
Factor Xa Inhibitors
Fondaparinux3
Rivaroxaban3
Apixaban13
150 mg PO bid4,7
No data
150 mg PO bid4,8
15 mg SC q12h9
1. For elective hip or knee arthroplasty, prophylaxis is recommended for a minimum of 10 days after surgery, and for hip arthroplasty, up to 35 days (WH
Geerts et al. Chest 2008; 133:3815).
2. Initial dose is 333 units/kg for unmonitored dosing regimen.
3. Dosage adjustments may be necessary in renal insufficiency.
4. Dose only FDA-approved for this indication.
5. Dose only FDA-approved for cancer patients x 30 days, then 150 IU/kg SC daily x 5 months (not to exceed 18,000 IU/day).
6. Monitor daily and adjust dose until results in therapeutic range (INR 2-3) for >24 hours.
7. S Schulman et al. N Engl J Med 2009; 361:1342.
8. A dose of 220 mg (two 110-mg capsules) once daily is approved for VTE prophylaxis in Canada.
9. Use of desirudin has only been studied for up to 12 days.
10. 5 mg if <50 kg, 7.5 mg if 50-100 kg, 10 mg if >100 kg.
11. Dose for adults >50 kg. Contraindicated for patients weighing <50 kg.
12. EINSTEIN Investigators. N Engl J Med 2010; 363:2499.
13. Not yet available in the US.
14. Botticelli Investigators Writing Committee. J Thromb Haemost 2008; 6:1313.
15. MR Lassen et al. Lancet 2010; 375:807.
64
Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011
Antithrombotic Drugs
Dosage
Aspirin1
Warfarin
Rivaroxaban
Dabigatran
Apixaban6
75-81 mg PO daily
2-10 mg PO daily2
20 mg PO daily3-5
150 mg PO bid4
5 mg PO bid7
1.
2.
3.
4.
5.
6.
7.
Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011
65
Antithrombotic Drugs
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
66
Treatment Guidelines
Guidelines
Treatment
from The Medical Letter
Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011
Introducing
Treatment Guidelines: Online Continuing Medical Education
Up to 24 credits included with your subscription
medicalletter.org/cme
For over 25 years, The Medical Letter has offered health care professionals continuing medical education (CME) with The Medical Letter on Drugs and Therapeutics.
We are now offering CME for Treatment Guidelines from The Medical Letter in an online format only, called the Online Series. Each Online Series is comprised of 6
monthly exams and is eligible for up to 12 credits. For those who just need a few credits, we also offer the Quick Online Credit Exam (earn up to 2 credits/12 questions).
For more information, please visit us at medicalletter.org/cme.
Choose CME from Treatment Guidelines from The Medical Letter and earn up to
24 Category 1 Credits per year in the format thats right for you:
Online Series - Answer 12 questions per issue online. Earn up to 2 credits/exam. Take up to 6 short exams per six-month series and earn up to a total of 12 credits.
The Online Series is included with a paid subscription to Treatment Guidelines.
Quick Online Credit Exam - Access content for any available issue, answer 12 questions online, and earn up to 2 credits for $12.00 (available to both subscribers and
non-subscribers).
ACCREDITATION INFORMATION:
ACCME: The Medical Letter is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Medical
Letter Inc. designates this enduring material for a maximum of 2 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the
extent of their participation in the activity. This CME activity was planned and produced in accordance with the ACCME Essentials and Policies.
AAFP: Treatment Guidelines from the Medical Letter Continuing Medical Education Program has been reviewed and is acceptable for up to 15 Prescribed credits by
the American Academy of Family Physicians. AAFP accreditation begins January 1, 2011. Term of approval is for 1 year from this date. Each issue is approved for 1.25
Prescribed credits. Credit may be claimed for 1 year from the date of each issue.
ACPE: The Medical Letter is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. This exam is
acceptable for 2.0 hour(s) of knowledge-based continuing education credit (0.2 CEU).
AANP and AAPA: The American Academy of Nurse Practitioners (AANP) and the American Academy of Physician Assistants (AAPA) accept AMA Category 1
Credit for the Physicians Recognition Award from organizations accredited by the ACCME.
AOA: This activity, being ACCME (AMA) approved, is acceptable for Category 2-B credit by the American Osteopathic Association (AOA). Physicians, nurse practitioners, pharmacists and physician assistants may earn 1 credit with this exam.
Physician Assistants: The National Commission on Certification of Physician Assistants (NCCPA) accepts AMA PRA Category 1 Credit(s) from organizations accredited by ACCME. NCCPA also accepts AAFP Prescribed credits for recertification. Treatment Guidelines is accredited by both ACCME and AAFP.
Physicians in Canada: Members of The College of Family Physicians of Canada residing in the US are eligible to receive Mainpro-M1 credits (equivalent to AAFP
Prescribed credits), and members residing in Canada are eligible to receive Mainpro-M2 credits due to a reciprocal agreement with the American Academy of Family
Physicians. Treatment Guidelines CME activities are eligible for either Section 2 or Section 4 (when creating a personal learning project) in the Maintenance of
Certification Program of the Royal College of Physicians and Surgeons of Canada (RCPSC).
MISSION:
The mission of The Medical Letter's Continuing Medical Education Program is to support the professional development of health care professionals including physicians, nurse practitioners, pharmacists and physician assistants by providing independent, unbiased drug information and prescribing recommendations that are free
of industry influence. The program content includes current information and unbiased reviews of FDA-approved and off-label uses of drugs, their mechanisms of action,
clinical trials, dosage and administration, adverse effects and drug interactions. The Medical Letter delivers educational content in the form of self-study material.
The expected outcome of the CME Program is to increase the participants ability to know, or apply knowledge into practice after assimilating, information presented
in materials contained in Treatment Guidelines.
The Medical Letter will strive to continually improve the CME program through periodic assessment of the program and activities. The Medical Letter aims to be a
leader in supporting the professional development of health care professionals through Core Competencies by providing continuing medical education that is unbiased
and free of industry influence. The Medical Letter is supported solely by subscription fees and accepts no advertising, grants or donations.
GOAL:
Through this program, The Medical Letter expects to provide the health care community with unbiased, reliable and timely educational content that they will use to
make independent and informed therapeutic choices in their practice.
LEARNING OBJECTIVES:
The objective of this activity is to meet the need of health care professionals for unbiased, reliable and timely information on treatment of major diseases. The Medical
Letter expects to provide the health care community with educational content that they will use to make independent and informed therapeutic choices in their practice.
Participants will be able to select and prescribe, or confirm the appropriateness of the prescribed usage of the drugs and other therapeutic modalities discussed in
Treatment Guidelines with specific attention to clinical evidence of effectiveness, adverse effects and patient management.
Upon completion of this activity, the participant will be able to:
1.
2.
3.
Explain the current approach to the management of a patient with arterial or venous thromboses.
Discuss the pharmacologic options available for prevention or treatment of arterial or venous thromboses or prevention of cardioembolic events in patients
with atrial fibrillation and compare them based on their efficacy, dosage and administration, potential adverse effects and drug interactions.
Determine the most appropriate therapy given the clinical presentation of an individual patient.
Privacy and Confidentiality: The Medical Letter guarantees our firm commitment to your privacy. We do not sell any of your information. Secure server software (SSL)
is used for commerce transactions through VeriSign, Inc. No credit card information is stored.
IT Requirements: Windows 98/NT/2000/XP/Vista/7, Pentium+ processor, Mac OS X+ w/ compatible process; Microsoft IE 6.0+, Mozilla Firefox 2.0+ or any other compatible Web browser. Dial-up/high-speed connection.
Have any questions? Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org
Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011
12. A 50-year-old man with atrial fibrillation asks his physician to recommend a treatment to reduce his risk of thromboembolic stroke.
You could tell him that:
a. once daily aspirin is a possible choice if he has no risk factors, but is less effective than warfarin
b. dabigatran is a new drug that may be as effective as warfarin
and does not require monitoring
c. rivaroxaban is a new drug that may be as effective as warfarin and does not require monitoring
d. all of the above
Issue 110
ACPE UPN: 379-0000-11-110-H01-P; Release: September 2011, Expire: September 2012
Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011