MTM essentials for anticoagulant management in cardiovascular disease
C. Michael White, PharmD, FCP, FCCP
Professor and Head, Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Conn.
Jiehyun Lee, PharmD
Adjunct Assistant Professor, University of Connecticut School of Pharmacy, Storrs, Conn. and Medication Management Clinic Supervisor, Backus Hospital, Norwich, Conn.
Abstract
Atrial fibrillation and venous thromboembolism are prevalent, complex diseases that increase morbidity and mortality while reducing patients’ quality of life. There has been a dramatic increase in anticoagulant choices available to prevent and treat thrombosis and prevent related complications. Pharmacists play an important role in the prevention and management of thrombosis and can help to ensure the safe and effective use of evidence-based therapies to optimize outcomes. This article provides a review of the clinical features of each of the main drug classes used orally to treat thrombosis, including information on adverse events, monitoring, and drug-drug interactions.
Faculty: C. Michael White, PharmD, FCP, FCCP and Jiehyun Lee, PharmD
Dr. White, PharmD, is professor and head of pharmacy practice, University of Connecticut School of Pharmacy, Storrs, Conn. Dr. Lee is adjunct assistant professor, University of Connecticut School of Pharmacy, Storrs, Conn, and medication management clinic supervisor for Backus Hospital, Norwich, Conn.
Faculty disclosure: Dr. White and Dr. Lee have no actual or potential conflict of interest associated with this article.
Disclosure of Discussions of Off-Label and Investigational Uses of Drugs: This activity may contain discussion of unlabeled/unapproved use of drugs in the United States and will be noted if it occurs. Nothing in the IME Program is intended to imply reimbursement by any government or private payer for the product use under discussion. The content and views presented in this educational program are those of the faculty and do not necessarily represent those of Drug Topics or University of Connecticut School of Pharmacy. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Goal: This educational activity for pharmacists is designed to review the pharmacological properties, safety and efficacy, and risk/benefit profile for the various anticoagulant medications used in cardiovascular diseases.
After participating in this activity, pharmacists will be able to:
· Review pharmacological properties of currently available oral anticoagulants
· Discuss the efficacy and safety of oral anticoagulants for various indications
· Discuss advantages and disadvantages of oral anticoagulants based on clinical settings
· Describe risk and benefit of oral anticoagulants for specific patient populations
The University of Connecticut School of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
Pharmacists are eligible to participate in the knowledge-based activity, and will receive up to 0.2 CEUs (2 contact hours) for completing the activity, passing the quiz with a grade of 70% or better, and completing an online evaluation. Statements of credit are available via the online system and your participation will be recorded with CPE Monitor within 72 hours of submission.
ACPE# 0009-9999-14-010-H01-P
Grant Funding: This activity is supported by an independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc.
Activity Fee: There is no fee for this activity.
Initial release date: 9/10/2014
Expiration date: 9/10/2016
To obtain CPE credit, visit www.drugtopics.com/cpe and click on the "Take a Quiz" link. This will direct you to the UConn/Drug Topics website, where you will click on the Online CE Center. Use your NABP E-Profile ID and the session code 14DT10-VXP89 to access the online quiz and evaluation. First-time users must pre-register in the Online CE Center. Test results will be displayed immediately and your participation will be recorded with CPE Monitor within 72 hours of completing the requirements.
For questions concerning the online CPE activities, e-mail: cpehelp@advanstar.com.
Background
The two most common indications for chronic antithrombotic therapy in the United States are stroke prevention in atrial fibrillation (SPAF) and prevention and treatment of venous thromboembolism (VTE). Atrial fibrillation (AF) is the most common sustained arrhythmia in the United States and increases the risk of dementia by two-fold,1,2 the risk of overall mortality by 40% to 90%,3-5 and the risk of stroke by four- to five-fold.6
Atrial fibrillation
To determine the need for SPAF, clinicians use the Congestive heart failure, Hypertension, Age ≥75, Diabetes mellitus, and prior Stroke, transient ischemic attack, or Vascular disease (CHA2DS2-VASc) scoring system.7 CHA2DS2-VASc assigns one point each for congestive heart failure, high blood pressure, and diabetes, vascular disease (prior myocardial infarction, peripheral arterial disease, or aortic plaque, age 65-74, or female gender and two points for age ≥75 or a previous stroke, transient ischemic attack, or thromboembolism.7 Scores of 0, 1, and >2 indicate a low, moderate, and high risk, respectively, of stroke or systemic thrombosis.7-9
The American College of Cardiology, American Heart Association, and Heart Rhythm Society (ACC/AHA/HRS) guidelines for AF management were updated in March of 2014.7 Class I recommendations are associated with much greater benefit than harm, with the difference between benefit and harm being incrementally weaker for IIa and IIb recommendations. Class III recommendations display therapies or procedures that should not be used either because there is no benefit or because of patient harm. Level A recommendations are based on strong clinical trial evidence; the evidence base is weaker for Level B and C recommendations.
For patients with nonvalvular AF and a CHA2DS2-VASc score of 0, it is reasonable to omit antithrombotic therapy (Class IIa, Level B) and no antithrombotic therapy, aspirin alone, or oral anticoagulant therapy can be used if the CHA2DS2-VASc score is 1 (Class IIb, Level C). Once the CHA2DS2-VASc score is 2 or greater, there is a need for antithrombotic therapy with either warfarin (Class I, Level A) or newer anticoagulants (dabigatran, rivaroxaban, apixaban; Class I, Level B).7 Edoxaban was not included in these guidelines but like the other newer oral anticoaguants, has compelling clinical trial evidence with noninferiority versus warfarin with similar or lower risks of bleeding (Table 1).10-13 Edoxaban will not be further mentioned in this article but is a promising future agent. Renal function should be evaluated prior to starting newer oral anticoagulants, when clinically indicated, and at least annually thereafter (Class I, Level B), warfarin is a recommended anticoagulant in AF patients with chronic kidney disease or hemodialysis (Class IIa, Level B) whereas dabigatran and rivaroxaban are specifically recommended against (Class III, Level C). Similarly, dabigatran should be avoided in patients with AF and mechanical heart valves (Class III, Level B).7
Warfarin is titrated to an international normalized ratio (INR) of 2.0 to 3.0 unless the patient has mechanical heart valves where the INR can be 2.0 to 3.0 or 2.5 to 3.5 depending on the location of the prosthesis (Class I, Level B).7 In patients who cannot tolerate anticoagulants but can tolerate antiplatelet therapy, the use of aspirin + clopidogrel was evaluated as an alternative to aspirin alone but this combination has better efficacy with a higher risk of bleeding versus aspirin, so the risk-benefit ratio is not clear. In patients with AF, aspirin is dosed at 81 to 325 mg once daily. In patients with chronic atrial flutter, it is prudent to use the same scoring system for thrombotic risk (Class I, Level C).7
Pharmacologic and pharmacokinetic differences among oral anticoagulants
Although major clinical trials have not demonstrated compelling differences in efficacy or risk between warfarin and dabigatran, rivaroxaban, apixaban, there are important pharmacologic and pharmacokinetic differences among these agents.10-19 The pharmacist is in a unique position to evaluate cases and recommend specific therapies to the healthcare team and to counsel patients on the attributes of one therapy versus another.
For AF, warfarin and rivaroxaban are once-daily options, whereas dabigatran and apixaban are dosed twice daily.14-19 No trials have assessed compliance with once- versus twice-daily anticoagulants. In a systematic review of 76 studies assessing the effect of dosing on compliance, patients taking a variety of once-daily therapies had similar compliance as those taking twice-daily therapies (79%±14% vs 69%±15%; P = not significant) but much better compliance than those requiring therapy three times or four times daily (65%±16% and 51%±20%, respectively; P < .05 for both vs once-daily therapy).20 In one study, although patients taking once- or twice-daily therapy demonstrated a similar mean percentage of doses consumed (89% vs 88%), patients taking the once-daily regimen had twice as many days with no therapy as those taking twice-daily medication.21 Warfarin is inconvenient to take; patients have been shown to miss therapy on 21.2% of days.22 Dabigatran, with a tartaric acid core, increases the risk of dyspepsia, which may affect compliance.10,18
The use of apixaban, rivaroxaban, and dabigatran should be avoided in patients with severe renal dysfunction (creatinine clearance [CrCl] <15 mL/min).17-19 Rivaroxaban and dabigatran should also be avoided in patients with CrCl of 15-30 mL/min.17,18 There are additional precautions or suggested dosage alterations for most of these agents when used in patients with lesser levels of renal impairment.14-19
In patients with hepatic impairment, warfarin, apixaban, and rivaroxaban should be used with caution or avoided, but dabigatran does not have this limitation.14-19
In patients with genetic polymorphisms in CYP2C9 (CYP2C9*2 or *3 alleles) or the vitamin K reductase-1 (VKOR-1) code, a warfarin dose reduction of approximately 20% to 30% is required.16,23 Warfarin interacts with CYP2C9 inducers and inhibitors, so concomitant use of these agents should be avoided or the patient’s INR should be monitored closely during the initiation or cessation of treatment with these interacting drugs.16,23 Apixaban and rivaroxaban are CYP3A4 substrates and interact with CYP3A4 inhibitors or inducers. Unlike with the INR for warfarin, it is difficult to use coagulation laboratory tests to assess the extent that these interactions are altering the risk for thrombosis or bleeding at the patient level in real time.17,19,24
Dabigatran does not demonstrate CYP drug interactions but is a substrate for P-glycoprotein.13,18,25 Use of dabigatran should be avoided when using the P-glycoprotein inducer rifampin, as this combination would reduce the efficacy of dabigatran.18 In patients with mild renal impairment, dabigatran should be used with caution when used concurrently with P-glycoprotein inhibitors that would accentuate anticoagulation, such as dronedarone and ketoconazole.18
As warfarin reduces the synthesis of the endogenous anticoagulants (protein C and S), hereditary or acquired deficiencies in these proteins are associated with tissue necrosis after warfarin administration. Concomitant heparin for 5 to 7 days during warfarin initiation is recommended in patients with known protein C and S deficiencies, although alternative oral anticoagulant therapy would be more convenient in such cases.16,23
Vitamin K-containing foods or nutritional supplements markedly reduce the efficacy of warfarin but do not affect the efficacy of other anticoagulants.16 Patients unable or unwilling to ingest a consistent amount of green leafy vegetables should seek out other anticoagulant options. All anticoagulants should be used with caution or avoided in patients consuming the following natural products: alfalfa, anise, bilberry, bladderwrack, bromelain, cat's claw, celery, chamomile, coleus, cordyceps, dong quai, evening primrose, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng (American, Panax, and Siberian), grape seed, green tea, guggul, horse chestnuts, horseradish, licorice, prickly ash, red clover, reishi, S-adenosylmethionine (SAM-e), sweet clover, turmeric, and white willow bark.26
Venous thromboembolism
Anticoagulants are essential for the treatment of VTE, which can manifest as deep vein thrombosis (DVT) and/or pulmonary embolism (PE). A venous thrombus can develop due to stasis of blood flow, endothelial injury, and/or hypercoagulability, three broad categories that are known as Virchow’s triad.27
Anticoagulation therapy is recommended for all patients with VTE, unless anticoagulation is contraindicated for certain conditions such as gastrointestinal bleeding. The 2012 American College of Chest Physicians (ACCP) guidelines, 9th edition, discuss VTE management in detail and make recommendations based on different grades of strength and evidence.28 Strong and weak recommendations are classified as Grades 1 and 2, respectively. These recommendations are based on high-quality (Grade A), moderate-quality (Grade B), or low-quality (Grade C) evidence.
Duration of anticoagulation therapy for VTE
Multiple patient factors must be thoroughly evaluated before making a decision on the duration of anticoagulation therapy. The duration of anticoagulation therapy must be long enough to treat an acute episode of VTE and prevent recurrent VTE in the future, but not so long that the risk of bleeding outweighs the risk of recurrent thrombosis. In addition, patient preference should be considered when determining the duration of anticoagulation therapy.28
To assess the risk of recurrent VTE, two factors must be carefully evaluated: whether the acute episode of VTE has been effectively treated and what the patient’s intrinsic risk of recurrent VTE is estimated to be. Efficacy of the treatment will depend mainly on the duration of anticoagulation therapy, and the risk of recurrent VTE will depend on the cause of acute VTE. Acute VTE is considered “provoked” if the cause of VTE is identifiable and reversible or “unprovoked” if there is no identifiable cause. After stopping anticoagulant therapy, the risk of recurrence after VTE provoked by a nonsurgical reversible risk factor is 5% after 1 year and 15% after 5 years, and after unprovoked VTE, is 10% after 1 year and 30% after 5 years.28 The location and severity of VTE also influences decisions regarding duration of therapy.28
Although most recommendations would not change based on differences in risk of bleeding, it is important to recognize risk factors for bleeding in order to identify patients who are at high risk for bleeding associated with anticoagulation therapy. The risk factors include age >65 years or >75 years, previous bleeding, cancer, metastatic cancer, renal failure, liver failure, thrombocytopenia, previous stroke, diabetes, anemia, antiplatelet therapy, poor anticoagulant control, comorbidity and reduced functional capacity, recent surgery, frequent falls, and alcohol abuse. Patients with 2 or more risk factors are considered to be at high risk for bleeding, and they have an eightfold risk of major bleeding compared to patients with low risk of bleeding (0 risk factor).28
For patients with provoked DVT or PE, 3 months of anticoagulation therapy is recommended over shorter or longer periods (Grade 1B).29-31 For unprovoked DVT or PE, at least 3 months of anticoagulation is recommended (Grade 1B), and after 3 months of treatment, the risk-benefit ratio should be evaluated to determine whether anticoagulation therapy should be continued for a longer period.28 This evaluation will heavily depend on the bleeding risk of the longer period of anticoagulation and the residual VTE risk.
To reduce the risk of recurrent DVT or PE, extended anticoagulation therapy can be considered, which is defined as longer than 3 months of treatment. Multiple studies suggest that extended anticoagulant therapy with conventional-intensity anticoagulation (target INR 2.5) reduces recurrent VTE by approximately 90%.28 Extended anticoagulation therapy is, however, associated with approximately a 2.6-fold increase in major bleeding.28 Thus, patients receiving extended therapy should be evaluated annually to ensure that current anticoagulation therapy is still safe and effective.28
Warfarin and parenteral anticoagulants for VTE
Historically, warfarin in combination with an initial parenteral anticoagulant has been the first choice for anticoagulation in patients with VTE. The ACCP guidelines discuss warfarin therapy extensively as this drug has demonstrated its effectiveness for VTE treatment and prevention with a long history of evidence.28
In patients who are treated with warfarin for acute DVT or PE, a parenteral anticoagulant such as low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux is recommended as bridge therapy (Grade 1B).32,33 Parenteral anticoagulation is initiated on the same day as warfarin therapy and should be continued for a minimum of 5 days and until the INR is 2.0 or above for at least 24 hours (Grade 1B).34,35 Warfarin should then be dosed to maintain a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) for the duration of treatment (Grade 1B).36
A number of studies have demonstrated the benefits of using a LMWH over either intravenous (IV) or subcutaneous (SC) UFH as bridge therapy with warfarin.37-41 The evidence suggests that LMWHs are associated with a lower recurrence of VTE, decreased incidence of major bleeding, and decreased mortality compared to IV or SC UFH. In addition, LMWH is easier to administer to outpatients and has a lower potential for heparin-induced thrombocytopenia.42 Fondaparinux has similar advantages and is as effective and safe as IV UFH in the initial treatment of VTE.43 Thus, the ACCP guidelines recommend LMWH or fondaparinux over IV UFH (both Grade 2C) and SC UFH (Grade 2B for LMWH; Grade 2C for fondaparinux) as the initial treatment option with warfarin. In general, SC UFH is not recommended because of its unpredictable pharmacokinetics.
New oral anticoagulants for VTE
Rivaroxaban, dabigatran, and apixaban have been studied in randomized controlled trials for the prevention of VTE after knee or hip replacement surgery. These trials have demonstrated that the three new oral anticoagulants are superior to or as effective as the standard therapy (enoxaparin 40 mg SC daily) without increasing the risk of bleeding.44-48 Rivaroxaban and apixaban are approved by the FDA for this indication, but dabigatran is not yet approved at the time this article is developed. The details on post-operative thromboprophylaxis for patients with orthopedic surgery are beyond the scope of this article and will not be discussed here.
In November 2012, rivaroxaban was approved by the FDA for the treatment of DVT or PE and for the prevention of recurrent DVT or PE after initial treatment. Two randomized, open-label, event-driven, noninferiority trials were conducted to evaluate the effectiveness of rivaroxaban (15 mg twice daily for 21 days, then 20 mg once daily) compared to standard therapy (enoxaparin and adjusted-dose vitamin K antagonist) for the treatment of DVT and PE. A pooled analysis of these two trials including more than 8200 patients showed that the primary efficacy outcome (the composite of fatal or nonfatal PE or DVT) was similar in the two groups (hazard ratio [HR], 0.89; 95% CI, 0.66-1.19; P < 0.001 for noninferiority).49 The safety outcome (major bleeding) was significantly lower in the rivaroxaban group than in the standard therapy group (HR, 0.54; 95% CI, 0.37-0.79; P = 0.002).49 The analysis suggested that rivaroxaban is as effective as standard therapy and is associated with a significantly lower rate of major bleeding. Use of this agent does not require initial treatment with a parenteral anticoagulant, which may be more convenient for patients.
A double-blind, randomized, event-driven superiority study including approximately 1200 patients also compared rivaroxaban alone (20 mg once daily) with placebo for extended treatment (additional 6 or 12 months) in patients who had already completed 6 to 12 months of treatment for VTE. In this study, rivaroxaban showed superior efficacy in preventing VTE (HR, 0.18; 95% CI, 0.09-0.39; P < 0.001) with four patients having nonfatal major bleeding (0.7%).50 This study suggests that extended therapy with rivaroxaban may improve the benefit-to-risk profile of anticoagulation and that the extended therapy may be beneficial even with the initial episode of VTE.50
In April 2014, dabigatran was approved by the FDA for the treatment of acute VTE in patients who have been treated with a parenteral anticoagulant for 5-10 days and for the prevention of recurrent VTE after initial treatment. In a randomized, double-blind, double-dummy trial in more than 2500 patients with acute VTE treated with LMWH or UFH for 5 to 11 days, dabigatran 150 mg twice daily was compared with warfarin.51 The primary outcome (recurrent symptomatic, objectively confirmed VTE and related deaths during 6 months of treatment) was similar in the two groups (HR, 1.08; 95% CI, 0.64-1.80; P < 0.001 for noninferiority).51 Major or clinically relevant nonmajor bleeding occurred less often in the dabigatran group than in the warfarin group (HR, 0.62; 95% CI, 0.45-0.84).51 Overall, dabigatran was noninferior to warfarin in patients with VTE recurrence and was associated with a lower risk of bleeding when used for the treatment of acute VTE.51
Two randomized, double-blind studies also compared dabigatran with warfarin (active control) and with placebo (placebo-control) for the extended treatment of VTE in patients who had completed at least 3 months of initial therapy.52 The two trials included more than 2800 patients and demonstrated that dabigatran was as effective as warfarin in the extended treatment of VTE (HR, 1.44; 95% CI, 0.78-2.64; P = 0.01 for noninferiority) with a lower risk of bleeding (HR, 0.54; 95% CI, 0.41-0.71).52 However, more acute coronary syndromes occurred in the dabigatran group than in the warfarin group. Although this result was initially concerning to health professionals, the FDA recently released the results of a new study in more than 134,000 Medicare patients showing that dabigatran has a risk of myocardial infarction similar to that of warfarin but carries a higher risk of gastrointestinal bleeding.53
Apixaban is not yet approved by the FDA for the treatment or prevention of VTE, but a Supplemental New Drug Application for this indication was submitted to the FDA in December 2013 and a decision on approval is expected in August 2014. A randomized, double-blind study including approximately 5400 patients compared apixaban (10 mg twice daily for 7 days, followed by 5 mg twice daily) with conventional therapy (SC enoxaparin, followed by warfarin). In terms of the primary efficacy outcome (recurrent symptomatic VTE or death related to VTE), apixaban was noninferior to conventional therapy (relative risk [RR], 0.84; 95% CI, 0.60-1.18; P < 0.001).54 The composite outcome of major bleeding and clinically relevant nonmajor bleeding was lower in apixaban group than in conventional-therapy group (4.3% versus 9.7%, respectively; RR, 0.44; 95% CI, 0.36-0.55; P < 0.001).54 This study suggests that apixaban alone is as effective as conventional therapy with significantly less risk of bleeding.54
Another randomized, double-blind study including more than 2400 patients compared two doses of apixaban (2.5mg and 5 mg, twice daily) with placebo for extended treatment (additional 12 months) in patients who had completed 6 to 12 months of anticoagulation therapy.55 Symptomatic recurrent VTE occurred in 8.8% of the placebo group, 1.7% of the 2.5-mg apixaban group (a difference of 7.2% points; 95% CI, 5.0-9.3; P < 0.001), and 1.7% of the 5-mg apixaban group (a difference of 7.0% points; 95% CI, 4.9-9.1; P < 0.001). The rates of major bleeding were similar; 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were similar as well; 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. This study suggests that extended therapy with either apixaban 2.5 mg or 5 mg twice-daily dosing reduces the risk of recurrent VTE without increasing the rate of major bleeding.55 Apixaban also has the advantage of not requiring initial treatment with a parenteral anticoagulant for the treatment of VTE.
Conclusion
In the past, patients were limited to warfarin therapy for oral anticoagulation. However, there are now several orally available options for anticoagulation in patients with AF and VTE. In this article we presented the clinical data for efficacy and safety and some of the main differences between agents that can drive treatment choice. It is important to utilize this information to make patient specific treatment choices and to use dosing regimens specific for the patient’s indication for therapy and other patient factors.
**PULL QUOTES**
The pharmacist is in a unique position to evaluate cases and recommend specific therapies to the healthcare team and to counsel patients on the attributes of one therapy versus another.
Multiple patient factors must be thoroughly evaluated before making a decision on the duration of anticoagulation therapy.
**Pause and Ponder Questions**
As there are many known P-glycoprotein inducers and inhibitors but only a few specific recommendations for avoidance or dose alterations when these agents are administered with dabigatran, what would you do if you ran into this issue?
Think of your patients who are currently on warfarin to prevent thromboembolism. Who may be a better candidate to switch over to a new oral anticoagulant? Who may be a better candidate to stay on warfarin rather than switching over to a new oral anticoagulant?
TEST QUESTIONS
1. According to the AHA/ACC/HRS guidelines, which of the following recommendations would be the strongest?
a. Class I, Level A
b. Class IIb, Level C
c. Class III, Level B
d. Class IIa, Level A
2. Patents with AF and a CHA2DS2-VASc score of 1 should receive which of the following regimens for stroke prevention?
a. Aspirin 81 to 325 mg
b. Warfarin to an INR of 2 to 3
c. Either aspirin 81 to 325 mg or warfarin to an INR of 2 to 3
d. Both aspirin and warfarin
3. Patents with AF and a CHA2DS2-VASc score of 3 should receive which of the following regimens for stroke prevention?
a. Aspirin 81 to 325 mg
b. Warfarin to an INR of 2 to 3
c. Either aspirin 81 to 325 mg or warfarin to an INR of 2 to 3
d. Both aspirin and warfarin
4. What do the AHA/ACC/HRS AF guidelines say about the use of dabigatran in patients with a CHA2DS2-VASc score of 2?
a. It is better than using rivaroxaban as an alternative
b. It is an acceptable alternative to warfarin but the level of evidence is not as strong
c. Warfarin is preferred over dabigatran due to superior efficacy
d. Dabigatran should not be used due to a high risk of major bleeding
5. Which anticoagulants are CYP3A4 substrates?
a. Rivaroxaban and edoxaban
b. Apixaban and warfarin
c. Apixaban and rivaroxaban
d. Dabigatran and edoxaban
6. Which anticoagulants are P-glycoprotein substrates?
a. Rivaroxaban
b. Apixaban
c. Apixaban
d. Dabigatran
7. If the CrCL is <10 mL/min, which anticoagulant is a safer choice?
a. Warfarin
b. Apixaban
c. Rivaroxaban
d. Dabigatran
8. If the patient had chronic kidney disease or hemodialysis, which choices do the AHA/ACC/HRS AF guidelines specifically recommend against?
a. Warfarin and rivarobaban
b. Apixaban and warfarin
c. Rivaroxaban and apixaban
d. Dabigatran and rivaroxaban
9. Which of the following anticoagulants have a drug-food interaction with vitamin K-containing foods?
a. Warfarin
b. Apixaban
c. Rivaroxaban
d. Dabigatran
10. Which of the following drugs needs to be used with caution or avoided in patients with protein C or S deficiency?
a. Rivaroxaban
b. Warfarin
c. Apixaban
d. Dabigatran
11. According to the 2012 ACCP guidelines, what is an appropriate duration of anticoagulation therapy for a patient who develops acute DVT for the first time due to a transient risk factor?
a. 3 months
b. 6 months
c. 12 months
d. Indefinitely
12. According to the 2012 ACCP guidelines, what is an appropriate duration of anticoagulation therapy for a patient who develops a second DVT without an identifiable cause and has a low risk of bleeding?
a. 3 months
b. 6 months
c. 12 months
d. Indefinitely
13. What are the three broad categories of Virchow’s triad?
a. Stasis of blood flow, ischemia, and hypercoagulability
b. Ischemia, endothelial injury, and hypercoagulability
c. Stasis of blood flow, endothelial injury, and hypercoagulability
d. Stasis of blood flow, endothelial injury, and ischemia
14. Which of the following anticoagulants is NOT FDA approved for the treatment of acute DVT or PE?
a. Warfarin
b. Rivaroxaban
c. Dabigatran
d. Apixaban
15. Which of the following anticoagulants does NOT require initial treatment with a parenteral anticoagulant for the treatment of acute DVT or PE?
a. Warfarin
b. Rivaroxaban
c. Dabigatran
d. All of the above
16. Which of the following anticoagulants can be given once daily for extended therapy to prevent the recurrence of VTE?
a. Rivaroxaban
b. Dabigatran
c. Apixaban
d. All of the above
17. For the treatment of acute DVT or PE with warfarin, how many days of initial treatment with a parenteral anticoagulant are needed according to the ACCP guidelines?
a. A minimum of 3 days
b. A minimum of 5 days
c. Until INR is 2.0 or above for at least 24 hours
d. b and c
18. Which of the following is the correct dosing of dabigatran for the treatment of DVT or PE?
a. 110 mg twice daily after 5 to 10 days of parenteral anticoagulation
b. 150 mg twice daily after 5 to 10 days of parenteral anticoagulation
c. 220 mg once daily after 2 to 5 days of parenteral anticoagulation
d. 440 mg once daily after 2 to 5 days of parenteral anticoagulation
19. What is the target INR range of warfarin therapy for the treatment of DVT or PE?
a. 1.5 to 2.5
b. 2 to 3
c. 2.5 to 3.5
d. 3 to 4
20. Which of the following statements is true regarding parenteral anticoagulation in the treatment of DVT or PE?
a. The ACCP guidelines recommend LMWH over UFH
b. The ACCP guidelines recommend fondaparinux over UFH
c. LMWH has a lower potential for heparin-induced thrombocytopenia
d. All of the above
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