Treatment Guidelines

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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.

Table 1. Drugs of Choice

Indication
Primary Prevention
Risk Factors
No Risk Factors
Secondary Prevention
Recent MI
Ischemic Stroke

ASPIRIN Aspirin irreversibly acetylates cyclooxygenase-1, blocking thromboxane synthesis and

inhibiting platelet activation and aggregation for the
lifetime of the platelet (5-7 days). Its use slightly
increases the risk of major bleeding. Aspirin can cause
asthma and other hypersensitivity symptoms in
aspirin-intolerant patients.
Aspirin prophylaxis reduces the incidence of MI and/or
death by 15-25% in patients with UA/NSTEMI,
STEMI or ischemic stroke, and in those undergoing PCI
or a coronary artery bypass graft (CABG). Aspirin can
also prevent MIs in asymptomatic men and ischemic
stroke in asymptomatic women, but the risk-benefit
ratio is less favorable because the thrombotic risk is
lower and the benefit in preventing thrombosis is offset
by a small increased risk of hemorrhagic stroke.1,2
DIPYRIDAMOLE A pyrimidopyrimidine derivative, dipyridamole (Persantine, and others) inhibits

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

LMWH or UFH or fondaparinux

+ warfarin

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

Low-dose UFH, LMWH

or fondaparinux
Low-dose UFH, LMWH
or fondaparinux
Fondaparinux or rivaroxaban or
dabigatran3 or LMWH or warfarin
Aspirin4 or warfarin or dabigatran
or rivaroxaban3 or apixaban5
Aspirin2

UFH = Unfractionated heparin; LMWH = Low-molecular-weight heparin

1. Some clinicians offer aspirin to women >65 and men >45 years old.
2. Or, if intolerant to aspirin, clopidogrel.
3. Not FDA-approved for this indication.
4. For patients at low risk.
5. Not yet available in the US.

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

Dipyridamole (IR) generic

Persantine (Boehringer Ingelheim)

75-100 mg PO qid

No dosage adjustment
required

Irreversible

Dipyridamole (ER)/aspirin2 generic

Aggrenox (Boehringer Ingelheim)

200 mg/25 mg PO bid

(morning and evening)

No dosage adjustment
required; do not use if
CrCl <10 mL/min

Irreversible

Clopidogrel Plavix (Sanofi Aventis)

300-600 mg PO loading dose,

75 mg PO once daily

No dosage adjustment
required

Irreversible

Prasugrel3 Effient (Lilly)

60 mg PO loading dose,
10 mg PO once daily4

No dosage adjustment
required

Irreversible, not dialyzable

Ticagrelor Brilinta (AstraZeneca)

180 mg PO loading dose,

90 mg PO bid

No dosage adjustment
required

Reversible5

Ticlopidine generic

250 mg PO bid

No dosage adjustment
required

Irreversible

Abciximab ReoPro
(Centocor/Lilly)

0.25 mg/kg bolus, then

0.125 mcg/kg/min IV
(max 10 mcg/min)

No dosage adjustment
required

Not known

Eptifibatide Integrilin (Merck)

180 mcg/kg bolus 1-2x

(10 min apart), then
2 mcg/kg/min IV

CrCl <50 mL/min:

reduce maintenance dose
to 1 mcg/kg/min

Irreversible, dialyzable

Tirofiban Aggrastat (Medicure)

0.4 mcg/kg/min x 30 min,

then 0.1 mcg/kg/min IV

CrCl <30 mL/min:

reduce dose by 50%

Irreversible, dialyzable

No dosage adjustment
required

Protamine can reverse

effects

Drug
Antiplatelet Drugs

GPIIb/IIIa Inhibitors

PCI: 25 mcg/kg bolus over 3 min,

then 0.1 mcg/kg/min IV6,7
Anticoagulants
Unfractionated Heparin generic

UA/NSTEMI: 60 units/kg bolus,

then 12 units/kg/hr IV
STEMI: 60 units/kg bolus,
then 12 units/kg/hr IV
PCI: 70-100 units/kg IV bolus,
titrate to ACT 250-300 sec8
(50-70 units/kg IV bolus if
GP IIb/IIIa used, titrate to ACT
200-250 sec)

ACT = Activated Coagulation Time

1. Irreversibility of antiplatelet drugs means that the effect persists for the lifetime of the platelet (5-7 days).
2. Should not be chewed or crushed.
3. Not recommended in patients >75 years-old, unless high risk, or in those with stroke or a history of TIA.
4. Reduce dose to 5 mg for patients <60 kg.
5. Recovery of platelet function after stopping the drug is about twice as rapid with ticagrelor as it is with clopidogrel.
6. Not an FDA-approved indication.
7. FG Kushner et al. Circulation 2009; 120:2271.
8. With Hemotec device and 300-350 sec with Hemochron device.

platelet uptake of adenosine and blocks adenosine

diphosphate (ADP)-induced platelet aggregation. It is
also available in combination with aspirin (Aggrenox,
and others).3 Dipyridamole can cause severe headache
and diarrhea, which tend to resolve with continued use.
A randomized, controlled trial (ESPRIT) in 2739
patients who had experienced a transient ischemic
attack (TIA) or minor stroke in the previous 6 months
found that a combination of extended-release dipyridamole (200 mg bid) and low-dose aspirin (30-325 mg

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

CrCl <30 mL/min:

UA/NSTEMI:
1 mg/kg SC once daily
STEMI:
30 mgIV bolus plus 1mg/kg SC,
then 1 mg/kg SC once daily11

Protamine
(~60% neutralized)

UA/NSTEMI: 120 IU/kg

(max 10,000 IU) SC q12h

CrCl <30 mL/min:

based on anti-Xa levels

Protamine
(~60% neutralized)

PCI: 0.75 mg/kg bolus

then 1.75 mg/kg/h IV

CrCl <30 mL/min:

decrease infusion to 1mg/kg/h

No antidote, dialyzable

2.5 mg SC once daily12,13

CrCl <30 mL/min:

do not use

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

Dalteparin Fragmin (Pfizer)

Direct Thrombin Inhibitor
Bivalirudin Angiomax
(The Medicines Co.)
Factor Xa Inhibitor
Fondaparinux6 generic
Arixtra (GSK)
Vitamin K Antagonist

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.

versibly inhibit P2Y12, a major ADP receptor on the

platelet surface, increasing the risk of bleeding for the
lifetime of the platelet (5-7 days). The delayed onset of
action of these agents (they are prodrugs that must be
metabolized to become active) can be problematic in
patients who require a rapid antithrombotic effect.
Ticlopidine can cause skin reactions, cytopenias and
thrombotic thrombocytopenic purpura; it has largely
been replaced by clopidogrel.
Patient response to clopidogrel is variable. Whether
those who are poor metabolizers of clopidogrel have a
higher incidence of cardiovascular events is controversial.6 Some clinicians recommend pharmacogenetic
testing for CYP450 polymorphisms before prescribing
a long course of clopidogrel.7 Proton pump inhibitors,
particularly omeprazole (Prilosec, and others), inhibit
CYP2C19 and can interfere with activation of clopidogrel, but the results of some studies suggest that they
do not increase adverse cardiovascular outcomes.8
Prasugrel appears to be more effective than clopidogrel, but is associated with a greater risk of bleeding.9
Prasugrel is not recommended for patients with a history of stroke or TIA, or those >75 years old unless
they are at high risk (diabetes or prior MI); the risk of
bleeding is greater in older patients, and the benefit is
less clear.

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

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63

Antithrombotic Drugs
Table 3. Drugs for Venous Thromboembolism
Drug

Dosage for Treatment

Dosage for Prophylaxis1

Initial: 80 units/kg IV bolus then 18 units/kg/hr or

250 units/kg SC2 then 250 units/kg q12h

5000 units SC q 8-12h

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

30 mg SC bid or 40 mg SC once daily

2500-5000 IU SC once daily
75 IU/kg SC4

2-10 mg PO once daily6

2-10 mg PO once daily6

150 mg PO bid4,7
No data

150 mg PO bid4,8
15 mg SC q12h9

5-10 mg SC10 once daily

15 mg PO bid for 3 weeks, then 20 mg once daily4,12
5-10 mg PO bid or 20 mg PO daily14

2.5 mg SC once daily11

10 mg PO once daily
2.5 mg PO bid15

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.

arterial access sites is the most common complication

of these drugs. GPIIb/IIIa inhibitors, particularly abciximab, can also cause profound acute thrombocytopenia.
PARENTERAL ANTICOAGULANTS
HEPARIN Heparins act by combining with plasma
antithrombin to form a complex that is more active
than antithrombin alone in neutralizing thrombin and
factor Xa. Unfractionated heparin (UFH) has numerous disadvantages compared to low-molecular-weight
heparin (LMWH): it is more likely to cause heparininduced thrombocytopenia and has a more variable
anticoagulant response that requires monitoring. It also
has advantages over LMWH, however, that have kept
it from becoming obsolete: its anticoagulant effect can
be more rapidly reversed and more completely neutralized by protamine; it is not cleared by the kidneys and
therefore may be safer in patients with renal insufficiency; and it directly inhibits the contact activation
pathway that is important in the genesis of thrombi in
stents, filters and catheter tips.
LMWH LMWHs, produced by cleaving UFH into
shorter chains, inhibit factor Xa more than they inhibit

64

thrombin. Compared to UFH, LMWHs have longer

half-lives that permit fewer doses per day, and their
greater bioavailability leads to a more predictable anticoagulant response. In clinical trials comparing them
with UFH, they have generally been at least as effective and as safe. Three LMWHs, enoxaparin (Lovenox,
and others), dalteparin (Fragmin) and tinzaparin
(Innohep), have been approved by the FDA; they generally appear to be similar, but in clinical trials in
patients with UA/NSTEMI, enoxaparin has been associated with better outcomes than dalteparin or tinzaparin. Enoxaparin has been at least as safe as UFH in
patients undergoing elective PCI.12
LMWHs are often used to treat or prevent venous
thromboembolism (VTE). For initial treatment of deep
vein thrombosis (DVT), LMWH is generally preferred
to UFH. In a controlled trial in an ICU (PROTECT),
dalteparin was not superior to UFH in preventing
DVT, the primary endpoint, but dalteparin-treated
patients had significantly fewer pulmonary emboli.13
FONDAPARINUX Fondaparinux (Arixtra, and
others), a synthetic analog of the pentasaccharide
sequence of heparin, binds antithrombin with high

Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011

Antithrombotic Drugs

affinity and inhibits factor Xa indirectly through

antithrombin without neutralizing thrombin. The drug
has a long half-life and requires injection only once
daily. Fondaparinux accumulates in patients with renal
insufficiency, which can be problematic in the elderly,
and is contraindicated in patients with a CrCl <30
mL/min.
Fondaparinux appears to be as effective and safe as
UFH or LMWH for prophylaxis and treatment of VTE
and much less likely to cause heparin-induced thrombocytopenia.14,15 It may also be used as an alternative
to UFH or LMWH in UA/NSTEMI or STEMI.12 In
patients who underwent PCI, however, fondaparinux
provided no added benefit and was associated with
more catheter thrombosis.16,17
DIRECT THROMBIN INHIBITORS Unlike
heparins and fondaparinux, direct thrombin inhibitors
inhibit clot-bound as well as circulating thrombin.
Bivalirudin (Angiomax), which is given IV and has a
short half-life, can be used instead of heparin in patients
undergoing PCI; in one controlled trial, it significantly
reduced the incidence of major bleeding compared to
unfractionated heparin, but it did not provide a net benefit in outcomes.18 In another study, however, in patients
with STEMI undergoing primary PCI, use of bivalirudin
alone resulted in lower death rates and less major bleeding than heparin plus a GPIIb/IIIa inhibitor.19
Desirudin (Iprivask) is a hirudin analog approved by
the FDA for prevention of VTE after hip arthroplasty.
It appears to be more effective than enoxaparin in preventing DVT after elective hip arthroplasty, but it must
be injected twice daily and can cause life-threatening
allergic reactions.20
ORAL ANTICOAGULANTS
WARFARIN (Coumadin, and others) Vitamin K
antagonists such as warfarin, which require monitoring, were for a long time the only oral anticoagulants
available. Anticoagulation with warfarin reduces the
risk of thromboembolic stroke in patients with atrial
fibrillation by 60% or more and is more effective for
this indication than antiplatelet therapy. With an annual rate of major bleeding of about 1-2% and an
absolute increase in the rate of intracranial hemorrhage
of about 0.2%, the benefits of warfarin far surpass the
risks. The main drawback of warfarin is the variability
in dosage requirements and the need for close monitoring to keep the international normalized ratio (INR)
in the therapeutic range. Recently, 3 new oral anticoagulants that do not require monitoring have achieved
good results in clinical trials.21

Table 4. Drugs for Atrial Fibrillation

Drug

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.

For patients at low risk.

Monitor daily until results in therapeutic range (INR 2-3) for >24 hrs.
Not FDA-approved for this indication.
Dosage adjustments may be necessary in renal insufficiency.
MR Patel et al. N Engl J Med 2011, Aug 10 (epub).
Not yet available in the US.
CB Granger et al. N Engl J Med 2011, Aug 28 (epub).

DABIGATRAN (Pradaxa) In a randomized trial

(RE-LY), fixed doses of the oral direct thrombin
inhibitor dabigatran were at least as effective and safe
as adjusted-dose warfarin in patients with atrial fibrillation followed for a median of 2 years.22 For treatment of acute VTE, fixed-dose dabigatran was also as
effective as adjusted-dose warfarin in preventing
recurrent VTE, and as safe.23 Unlike warfarin, however, the anticoagulant effect of dabigatran is irreversible, which is problematic if bleeding occurs or
emergency surgery is needed. It also must be taken
twice daily, a potential disadvantage for compliance
with long-term use.
RIVAROXABAN (Xarelto) In one study, the oral
direct factor Xa inhibitor rivaroxaban was non-inferior
to enoxaparin followed by warfarin for acute and continued treatment of VTE, with no increase in major
bleeding.24 It is approved by the FDA for prophylactic
use after knee or hip replacement and for prevention of
stroke and systemic embolism in patients with nonvalvular atrial fibrillation (20 mg once daily).
Rivaroxaban was more effective than enoxaparin for
prophylactic use after knee or hip replacement, with no
significant increase in bleeding.25 In another trial
(ROCKET AF), it was non-inferior to warfarin for prevention of stroke or systemic embolism in patients
with non-valvular atrial fibrillation.26,27 Rivaroxaban
requires no monitoring and is taken once daily.
APIXABAN (Eliquis) Another factor Xa inhibitor,
apixaban, which has not yet been approved by the
FDA for any indication, was more effective than warfarin in a randomized trial (ARISTOTLE) in preventing stroke or systemic embolism in patients with atrial
fibrillation, with a lower rate of major bleeding.28 In 2
other randomized controlled trials, apixaban was more
effective than once-daily enoxaparin in preventing
VTE after knee or hip replacement, without causing an
increase in bleeding.29,30 In high-risk patients after an
acute coronary syndrome, however, addition of apixaban to antiplatelet therapy increased major bleeding
and did not provide any benefit.31

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

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A Kastrati et al. Bivalirudin versus unfractionated heparin during percutaneous coronary intervention. N Engl J Med 2008; 359:688.
GW Stone et al. Bivalirudin during primary PCI in acute myocardial
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MR Patel et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883.
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CB Granger et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011 Aug 27 (epub).
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trial. Lancet 2010; 375:807.
30. MR Lassen et al. Apixaban versus enoxaparin for thromboprophylaxis
after hip replacement. N Engl J Med 2010; 363:2487.
31. JH Alexander et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011 Jul 24 (epub).

Coming Soon in Treatment Guidelines:

Drugs for Postmenopausal Osteoporosis
Adult Immunization

Treatment Guidelines
Guidelines

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EDITOR IN CHIEF: Mark Abramowicz, M.D.
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Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011

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Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011

DO NOT FAX OR MAIL THIS EXAM

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Issue 110 Questions

1. In patients with acute coronary syndrome, aspirin prophylaxis
reduces the incidence of myocardial infarction and/or death by:
a. 5-10%
b. 15-25%
c. 50-75%
d. 90-95%
Issue 110

7. Which of the following is a low-molecular-weight heparin used to

treat or prevent venous thromboembolism?
a. enoxaparin
b. fondaparinux
c. bivalirudin
d. desirudin
Issue 110

2. Proton pump inhibitors or CYP450 polymorphisms may affect the

activation of:
a. ticagrelor
b. abciximab
c. clopidogrel
d. fondaparinux
Issue 110

8. Fondaparinux can be used:

a. for prophylaxis of venous thromboembolism
b. for treatment of venous thromboembolism
c. for unstable angina/non-ST segment elevation myocardial
infarction (UA/NSTEMI)
d. all of the above
Issue 110

3. A boxed warning against using >100 mg of aspirin per day is

included in the labeling of:
a. clopidogrel
b. ticlopodine
c. prasugrel
d. ticagrelor

9. Unlike heparins and fondaparinux, direct thrombin inhibitors:

a. inhibit clot-bound as well as circulating thrombin
b. inhibit factor Xa
c. inhibit P2Y12
d. none of the above
Issue 110

4. An 80-year-old man undergoing knee replacement surgery asks

his physician to recommend an oral treatment for prevention of
venous thromboembolism. Which of the following would be an
appropriate choice for this patient?
a. dalteparin
b. tinzaparin
c. rivaroxaban
d. fondaparinux
Issue 110

10. Anticoagulation with warfarin reduces the risk of thromboemboic

stroke in patients with atrial fibrillation by:
a. > 60%
b. > 80%
c. > 90%
d. > 70%
Issue 110

5. Compared to unfractionated heparin, low-molecular-weight

heparin:
a. has a more predictable anticoagulant response
b. has a shorter half-life
c. is more completely neutralized by protamine
d. is more likely to cause heparin-induced thrombocytopenia
Issue 110

11. Although not FDA-approved for this indication, rivaroxaban was

non-inferior to warfarin for prevention of stroke or systemic
embolism in patients:
a. with diabetes
b. with non-valvular atrial fibrillation
c. undergoing hip arthroplasty
d. undergoing knee arthroplasty
Issue 110

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

6. Compared to low-molecular-weight heparin, unfractionated

heparin:
a. has a more variable anticoagulant response
b. can be reversed more rapidly
c. may be safer in patients with renal insufficiency
d. all of the above
Issue 110

Treatment Guidelines from The Medical Letter Vol. 9 ( Issue 110) October 2011