A technician s guide to new and old oral anticoagulants

Transcription

1 By: Jon P. Wietholter, Pharm D, BCPS, Clinical Associate Professor, WVU School of Pharmacy, Internal Medicine Clinical Pharmacist, WVU-Medicine Ruby Memorial Hospital Author Disclosures: Jon P. Wietholter and the DSN editorial and continuing education staff do not have any actual or potential conflicts of interest in relation to this lesson. Universal program number: H01-T CE Broker tracking number: Activity type: Knowledge-based Initial release date: Dec. 15, 2016 Planned expiration date: Dec. 15, 2019 This program is worth one contact hours (0.1 CEUs). Target Audience Technicians in community-based practice. Program Goal To compare and contrast the role of new oral anticoagulants as compared with warfarin. Learning Objectives: Upon completion of this program, the pharmacy technician should be able to: 1. List common uses for oral anticoagulants 2. Identify adverse effects associated with oral anticoagulants 3. Recall cost differences among available anticoagulant therapies To obtain credit: Complete the learning assessment and evaluation questions online at DrugStoreNewsCE.com. A minimum test score of 70% is needed to obtain a statement of credit. Official statements of credit will be available only at CPE Monitor (NABP. net). Please verify that your correct personal NABP e-profile ID and four-digit MMDD date of birth are included in your DSN CE profile before completing the lesson to ensure accurate transmission of credit to CPE Monitor. Questions: Contact the DSN customer service team at drsnce@ LF1925.com. Drug Store News is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. A technician s guide to new and old oral anticoagulants INTRODUCTION Before the Food and Drug Administration, or FDA, approved dabigatran etexilate mesylate (Pradaxa ) for the prevention of stroke or systemic embolism in nonvalvular atrial fibrillation patients in 2010, there was a simple, consistent answer to which oral anticoagulant should be used warfarin. Since 2010, dabigatran has been joined by rivaroxaban (Xarelto, 2011), apixaban (Eliquis, 2012) and edoxaban (Savaysa, 2015) in this class of medications referred to as the newer oral anticoagulants. Subsequently, recent guidelines have suggested that the newer oral anticoagulants should now be the preferred agents for multiple indications, including the prevention of stroke or systemic embolism in nonvalvular atrial fibrillation, the treatment of deep vein thrombosis, or DVT, or pulmonary embolism, or PE. 1-2 Because oral anticoagulants can be used for multiple indications, a pharmacy technician should be able to understand the differences in FDA-approved indications, safety and efficacy profiles of all the available agents. REVIEW OF ORAL ANTICOAGULANT INDI- CATIONS All four of the newer oral anticoagulants have been compared to the previous gold-standard (warfarin titrated to an INR of 2-3) for the prevention of stroke or systemic embolism in nonvalvular atrial fibrillation, and have gained FDA approval for this indication. 3-6 From an efficacy standpoint, all four newer oral anticoagulants were at least noninferior to warfarin therapy when evaluating rates of stroke and/or systemic embolism. From a safety standpoint, no significant increases in the incidence of major bleeds occurred with any of the four newer oral anticoagulants when compared to warfarin. More importantly, both apixaban and edoxaban were found to cause significantly less major bleeding than warfarin, with apixaban being the only agent across all dosing ranges within its trial that did not significantly increase gastrointestinal bleed rates. 5-6 In summary, all four newer oral anticoagulants are at least non-inferior when compared to warfarin in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation. The recommended dosages and indications are found in Table 1. Regarding the treatment of DVT/ PE, all four of the newer oral anticoagulants also have been compared to the previous gold-standard (warfarin titrated to an INR of 2-3) and have gained FDA approval for this indication From an efficacy standpoint, all four newer oral anticoagulants were shown to be noninferior to warfarin therapy when evaluating rates of recurrent DVT/ PE s. From a safety standpoint, none of the four newer oral anticoagulants had a significant increase in rates of major or clinically relevant bleeding. Dabigatran, apixaban and edoxaban actually showed a significant reduction in bleeding rates, while rivaroxaban did not Apixaban had the largest absolute reduction in major or clinically relevant bleeding rates 4.3% vs. 9.7% with warfarin. 10 In summary, all four newer oral anticoagulants are non-inferior when compared to warfarin in the prevention of recurrent DVT/PE. Additionally, three of the four newer oral anticoagulants dabigatran, rivaroxaban and apixaban have been compared to the previous gold-standard (enoxaparin) and are FDA approved in the United States for the prophylaxis of DVT/PE after hip replacement surgery, and two rivaroxaban and apixaban have 1 DECEMBER

2 Table 1 Current dosage recommendations for oral anticoagulants Warfarin sodium Dabigatran etexilate mesylate Rivaroxaban Apixaban Edoxaban NONVALVULAR ATRIAL FIBRILLATION Individualized dosing to attain an INR of mg PO taken twice daily Clcr is 15-to-30 ml/min: 75 mg PO taken twice daily Clcr is less than 15 ml/ min: Not recommended 4 20 mg PO taken daily with dinner If Clcr is 15-to-50 ml/ min: 15 mg PO taken daily with dinner 15 ml/min 5 mg PO taken twice daily 2.5 mg PO taken twice daily if patient has two or more of the following: - Age is 80 years old or older - Weight is 60 kg or less; - SCr is more than 1.5 mg/dl 60 mg PO taken daily If Clcr is 15-to-50 ml/ min: 30 mg PO taken daily Avoid if Clcr is more than 95 ml/min,or if Clcr is less than 15 ml/min been compared to enoxaparin and are FDA approved for the same indication after knee replacement surgery Dabigatran also has been studied after knee replacement surgery, but has not been approved for this indication at this time From an efficacy standpoint, rivaroxaban was shown to be superior to enoxaparin in all studies, while dabigatran and apixaban were shown to be superior to enoxaparin in certain trials, while showing inferiority in others. Interestingly, the trials that showed inferiority to enoxaparin compared dabigatran and apixaban to 30 mg of enoxaparin taken twice daily (the currently accepted dose for this indication), while the trials that showed superiority compared dabigatran and apixaban to 40 mg of enoxaparin taken daily. From a safety standpoint, no significant DVT/PE TREATMENT Individualized dosing to attain an INR of mg PO taken twice daily after 5-to-10 days of parenteral anticoagulation Clcr is less than 30 ml/ min: Not studied 15 mg PO taken twice daily for three weeks, then 20 mg PO taken daily 30 ml/min 10 mg PO taken twice daily for seven days, then 5 mg PO taken twice daily 60 mg PO taken daily after 5-to-10 days of parenteral anticoagulation If patient weighs 60 kg or less: 30 mg PO taken daily If Clcr is 15-to-50 ml/ min: 30 mg PO taken daily 15 ml/min DVT/PE PROPHYLAXIS AFTER KNEE OR HIP REPLACEMENT SURGERY Not currently FDA approved for this indication Only Indicated after hip replacement surgery 110 mg PO x1, then 220 mg PO taken daily 1 Clcr is 30 ml/min or less: Not studied 10 mg PO taken daily 30 ml/min 2.5 mg PO taken twice daily Not currently FDA approved for this indication PATIENT SCENARIO 1 PJ is a 55-year-old male arriving at the pharmacy with a new prescription for apixaban 5 mg PO twice daily. As the technician adds the patient profile information, she records PJ s allergies and medical history, including his new mechanical aortic valve that was surgically placed one week ago. The technician completes the data entry and positions the order within workflow as STAT or waiting patient. PJ decides to pick up a few items, while he waits for the prescription. As the prescription is filled, what action should the pharmacy technician take? Discussion The pharmacy technician must immediately alert the pharmacist of the information PJ provided. None of the newer oral anticoagulants have proven safety and efficacy in mechanical heart valve patients at this time. The technician did a great job matching the indication to the medication, and caught a potential medication error. The patient will likely need to be placed on both warfarin and a parenteral anticoagulant until his INR is within the goal INR range (likely 2.0 to 3.0 with a mechanical aortic valve). The pharmacist should call the prescriber to confirm the indication for oral anticoagulation and recommend against the use of apixaban, if it is determined that a mechanical aortic valve is indeed the indication requiring anticoagulation. bleeding differences occurred in any of the aforementioned trials except for one where apixaban had significantly less bleeding when compared with enoxaparin. 14 In summary, dabigatran, rivaroxaban and apixaban are all FDA-approved options for the prophylaxis of DVT/PE in patients after hip replacement surgery, while rivaroxaban and apixaban also are FDA approved after knee replacement surgery. Rivaroxaban appears to have the best efficacy data, while apixaban appears to have the best overall safety profile in these patient populations. Finally, none of the newer oral anticoagulants have documented safety and efficacy with patients who have mechanical heart valves. If a pharmacy technician discovers that this is the indication for a newer oral anticoagulant prescription, the pharmacist should be notified and a call should be made to the patient s prescriber to discuss other potential options for anticoagulation. In this patient population, warfarin is still the medication of choice, and INR goals should be titrated appropriately based off which valve was replaced and which type of valve was used to replace the native one. ADVERSE EFFECTS Warfarin is known to cause multiple adverse effects, with potential bleeding being the most concerning. Bleeding can occur from virtually any anatomical site when using warfarin, ranging from minor epistaxis to fatal intracranial hemorrhage. Patientspecific factors, potential drug-drug interactions, a prior history of bleeding and genetics can all amplify a patient s bleeding risk while taking warfarin. A pharmacy technician should be able to pick up on signs and symptoms of over-anticoagulation with warfarin, including increased incidence of bleeding and/or unusual bruising on patients. If either is noticed, the pharmacist should be notified immediately and referral to the patient s primary care physician, DECEMBER

3 or PCP, may be warranted. Furthermore, if a patient presents to the pharmacy complaining of signs and symptoms of an intracranial bleed (e.g., dizziness, headache, lethargy); a retroperitoneal hematoma (e.g., abdominal pain, ecchymosis over the abdomen); gastrointestinal bleeding (e.g., black/ tarry or bright red stools, hematemesis); or hematuria, the pharmacy technician should immediately alert the pharmacist or refer the patient to a PCP or the nearest emergency department, depending on the severity of symptoms. When evaluating the newer oral anticoagulants, all four agents still have bleeding in common as a major concern. These bleeding events encompass a wide scope of bleeds, ranging from minor wound secretion to gastrointestinal bleeds. Other noteworthy adverse effects that occur in more than 3% of patients include anemia (dabigatran and apixaban), back pain (rivaroxaban), gastritis (dabigatran), abnormal liver function tests (dabigatran and edoxaban), nausea (rivaroxaban and apixaban) and rash (edoxaban). Additionally, dabigatran is absorbed more effectively in an acidic environment and, because of this, it has been formulated with a tartaric acid core, which leads to more frequent dyspepsia. Dabigatran also warrants extreme caution with patients age 75 years old or older. In this age group, it has been linked to multiple types of hemorrhage, including hemorrhagic strokes and gastrointestinal bleeds. When presented with a new prescription for dabigatran in this age group, the pharmacy technician should confirm that this is the best anticoagulant option for the patient with the pharmacist. Patients should never discontinue taking an anticoagulant without the knowledge and approval of the prescriber. If the technician suspects that a patient may be considering the stoppage of an anticoagulant, the pharmacist must be alerted so that counseling can be provided on the dangers of discontinuing anticoagulants prematurely. Unless the patient has completed an appropriate duration of therapy or has a significant bleeding event, the newer oral anticoagulants should not be discontinued prior to discussing potential alternate options with the prescriber of the anticoagulant. Thrombotic events appear to happen at an increased rate when the newer oral anticoagulants are discontinued early. One last component that must be mentioned is the availability of reversal agents for the oral anticoagulants. Warfarin s effect can be reversed by providing either oral or parenteral phytonadione (vitamin K), which allows for renewed production of vitamin-k dependent clotting factors. However, phytonadione has an onset of action of 6-to-10 hours (orally) or 1-to-2 hours (parenterally), and a peak effect at 24-to-48 hours (orally) and 12-to-14 hours (parenterally), which may be too delayed in certain scenarios. Furthermore, with patients in high-risk situations (e.g., mechanical heart valves), the benefits and risks of reversing the anticoagulant effects of warfarin must be weighed very carefully. Blood products, including, but not limited to, fresh frozen plasma, or FFP, and prothrombin complex concentrate, or PCC, also may be used to reverse the effects of warfarin in scenarios where rapid reversal of its effects is warranted. Regarding the newer oral anticoagulants, many physicians have been hesitant to switch to them due to lack of a reversal agent. However, in 2015, idarucizumab (Praxbind ) was approved after it showed the ability to reverse the effects of dabigatran within four hours and restored hemostasis within 11 hours. 23 In addition, two experimental agents are currently being evaluated for reversal of the effects of apixaban and rivaroxaban (andexanet alfa) and edoxaban (ciraparantag). Preliminary data suggests that these experimental agents will reverse the effects of these factor Xa inhibitors within 10 minutes of administration While these agents are only available parenterally and are not likely to be seen in the community setting, knowledge of the availability of these reversal options is pertinent when considering the appropriate selection of an oral anticoagulant. KEY COUNSELING AND MONITORING PARAMETERS 26 Multiple key counseling points exist when it comes to use of the newer oral anticoagulants. Technicians should be aware of the following aspects regarding each of the agents, and should be able to advocate for the patient to receive appropriate counseling with the pharmacist. When working at the out-window, it is important to call the PATIENT SCENARIO 2 pharmacist for counseling when patients pick up oral anticoagulants. Dabigatran The peak effect of dabigatran can be delayed by up to two hours with food. However, food does not affect its bioavailability, so it can be taken without regard to meals. As mentioned in the adverse events section above, patients should know about the dyspepsia that is commonly encountered with dabigatran use. Additionally, dabigatran, which is only good for four months once dispensed from the pharmacy, should be kept in its original container. Patients also should be informed not to open, chew or crush dabigatran capsules in any manner because doing this can drastically increase absorption of the medication and lead to increased adverse effects. The dose of dabigatran needs to be adjusted with renal insufficiency, beginning at a creatinine clearance, or Clcr, of 30 ml/min. If the patient is planning to undergo surgery, dabigatran should be discontinued 1-to-2 days prior to surgery with patients who have good renal function (Clcr of 50 ml/min or greater) or 3-to-5 days prior to surgery with patients who have reduced renal function (Clcr less than 50 ml/min). When transitioning from warfarin therapy, a patient should have an international normalized ratio, or INR, of less than two prior to initiating dabigatran. When converting from dabigatran to warfarin, patients must take both medications for a few days. The combination therapy should contain both dabigatran and warfarin for three days with patients who have good renal function (Clcr of 50 ml/min or greater); two days with patients who have somewhat-reduced renal function (Clcr 31- to-50 ml/min); and one day with patients who have significantly reduced renal function (Clcr 15-to-30 ml/min). After completing these bridging timeframes, dabiga- JW, a well-known 62-year-old female patient, arrives at the pharmacy. As she talks with the technician, JW mentions that she would like to speak with the pharmacist about nose bleeds that she has been having. While the technician works with JW, she notices that JW appears very pale and has a few bruises on her arms. While the pharmacist is counseling another patient, the technician pulls up JW s medication profile and notices that she filled her first prescription for rivaroxaban one week ago. At this point, what would be the appropriate steps for the pharmacy technician to take? Discussion JW could potentially be bleeding from the new rivaroxaban prescription. Due to her complaints and her noticeable pale skin color, the pharmacy technician should immediately alert the pharmacist and JW should be sent to her PCP or an emergency department without delay. All oral anticoagulants have the potential to induce bleeds (e.g., epistaxis) and increase bruising. Such adverse effects could definitely be caused by rivaroxaban. If the bleeding is severe enough, agents are available (or currently being studied) that may aid in the reversal of the anticoagulant effect of rivaroxaban, but these must be administered in an inpatient setting. Thus, JW should be referred to an appropriate facility immediately. 3 DECEMBER

4 Table 2 Pricing data for currently available oral anticoagulants 28 STRENGTH QUANTITY WHOLESALE ACQUISI- TION COST (WAC) PACKAGE PRICE AVERAGE WHOLESALE PRICE (AWP) AWP UNIT PRICE Warfarin sodium 1 1 mg 100 Ranging from $7.74 to 2 mg $61.08 Dabigatran etexilate mesylate 2.5 mg 3 mg 4 mg 5 mg 6 mg 7.5 mg 10 mg Ranging from $58.30 to $ mg 60 $ $ $7 110 mg 150 mg Rivaroxaban 10 mg 30 $ $ $ mg 20 mg Apixaban 2.5 mg 60 $ $ $ mg Edoxaban 15 mg 30 $ $ $ mg $ $ mg $ $ The pricing data provided for warfarin sodium does not include the cost of INR blood draws that are required to monitor the efficacy and safety of therapy. Ranging from 58 cents to $1.02 tran can then be discontinued. Rivaroxaban The usual dose of rivaroxaban for the treatment of DVT/PE is 15 mg taken twice daily for the first 21 days of therapy. Consult the pharmacist if a patient ever reports forgetting a dose. The patient must be instructed to take both 15 mg doses (30 mg) at his or her earliest convenience, if a dose is missed. Rivaroxaban also has some flexibility with administration. Rivaroxaban tablets can be crushed and immediately mixed with applesauce prior to use, if a patient is having trouble swallowing tablets. Due to its heavy involvement at CYP3A4, grapefruit juice may interact with apixaban and patients will need to be counseled by the pharmacist to avoid this combination whenever possible. When taking rivaroxaban doses greater than 15 mg, patients should take the medication with food typically with the evening meal. Rivaroxaban requires dosage adjustment beginning at a Clcr of 50 ml/min. From a surgical perspective, rivaroxaban should be discontinued 24 hours prior to surgery. When converting from warfarin, a patient should have an INR of less than 3 prior to initiating rivaroxaban. When converting to warfarin, both warfarin and a parenteral anticoagulant should be initiated at the time of the next scheduled rivaroxaban dose. Apixaban Apixaban has some specific considerations. The medication can be crushed and mixed with a dextrose-containing solution immediately before use, if a patient is having trouble swallowing tablets. It can be taken without regard to food. Due to its heavy involvement at CYP3A4, grapefruit juice may interact with apixaban and patients will need to be counseled by the pharmacist to avoid this combination whenever possible. Apixaban dosing appears to be affected by extreme body weights, with a 20%-to-30% increase in drug levels in patients weighing less than 50 kg, and a 20%- to-30% decrease in drug levels in patients weighing more than 120 kg. From a surgical perspective, it is currently recommended to discontinue apixaban therapy 24 hours prior to minor surgery and 48 hours prior to moderate-high risk surgery. When converting from warfarin, a patient should have an INR of less than two prior to initiating apixaban. When converting to warfarin, both warfarin and a parenteral anticoagulant should be initiated at the time of the next scheduled apixaban dose. Apixaban is the only pregnancy category B agent amongst the oral anticoagulants, and should be the preferred agent in this patient population. Also, apixaban is unique in that it requires either older age (more than 80 years old) or low body weight weighing 60 kg or less) to be combined with a serum creatinine of 1.5 mg/dl or greater prior to having to decrease its dose. Edoxaban Body weight appears to create dosing DECEMBER

5 issues with edoxaban as patients weighing 60 kg or less require dosage adjustment when being used as treatment for DVT/ PE. Edoxaban can be taken without regard to food and requires a dosage adjustment beginning at a Clcr of 50 ml/min. From a surgical perspective, it currently is recommended to discontinue edoxaban therapy 24 hours prior to surgery. When converting from warfarin, a patient should have an INR of less than 2.5 prior to initiating edoxaban. When converting to warfarin, the dose should be decreased to 30 mg for patients on 60 mg of edoxaban when warfarin is initiated. For patients on 30 mg of edoxaban, the dose should be decreased to 15 mg when warfarin is initiated. Edoxaban should then be discontinued once the INR is more than two. Refer to Table 1 for indication-specific, weight-based and renaldosage adjustments for each of the newer oral anticoagulants. COST OF THERAPY: After discussing the safety and efficacy of the newer oral anticoagulants, there is one last pertinent piece of information that may aid in the selection of an oral anticoagulant for a particular patient: cost. Based solely off pricing data, warfarin holds a clear edge. Warfarin s average wholesale price, or AWP, unit price ranges from roughly 50 cents to $1. Compared with the PRACTICE POINTS newer oral anticoagulants, AWP unit price range is roughly $7 to $14. This shows a clear financial advantage to the use of warfarin. However, these numbers don t give the entire picture. Warfarin requires INR monitoring that can range from daily (upon initiation of therapy in high-risk patients) to every couple of months once a stable warfarin dose has been determined. This additional monitoring cost is avoided with the newer oral anticoagulants due to their lack of a need for therapeutic drug monitoring at this current time. Additionally, all four of the newer oral anticoagulants have patient assistance programs, or PAPs, and/ or savings cards that can be used in situations where patients are unable to afford these medications. With their efficacious superiority over warfarin, the utility of these PAPs may create a win-win situation for patients, allowing them to receive the most effective medication possible for their specific indication, while not having to spend exorbitant amounts of money out of pocket to receive these newer agents. See Table 2 for pricing information. CONCLUSION According to recent guideline recommendations, it should be expected that the newer oral anticoagulants will continue to grow in popularity, particularly when all three potential reversal agents gain FDA approval. Knowing appropriate FDA-approved indications, the safety and efficacy profiles of each agent and the potential cost of each of the oral anticoagulants can aid the pharmacy technician in his or her understanding of these newer oral anticoagulants and their appropriate utility. According to currently available data for specific indications, dabigatran, apixaban and edoxaban all cause significantly less bleeding, while rivaroxaban is not significantly different when compared with warfarin therapy. Knowing the unique adverse effects of each of the newer oral anticoagulants is vital with dabigatran s potential to induce dyspepsia being the one most likely to be seen by pharmacy technicians in a community-pharmacy setting. While the newer oral anticoagulants are more expensive than warfarin, their improved efficacy and safety profiles, as well as the presence of patient assistance programs, should make them the preferred agents for most patients needing oral anticoagulant therapy. 1 Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2): doi: /j. chest Guyatt GH, Akl EA, Crowther M, et al. Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2_suppl):7S-47S. doi: /chest.1412s3. 3 Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2009;361: Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med 2011;365: Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2011;365: Guigliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2013;369: Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus Warfarin in the Treatment of Acute Venous Thromboembolism. N Engl J Med 2009;361: The EINSTEIN Investigators. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med 2010;363: The EINSTEIN-PE Investigators. Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism. N Engl J Med 2012;366: Agnelli G, Buller HR, Cohen A, et al. Oral Apixaban for the Treatment of Acute Venous Thromboembolism. N Engl J Med 2013;369: The Hokusai-VTE Investigators. Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism. N Engl J Med 2013; 369: Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Total Knee Arthroplasty. N Engl J Med 2008;358: Turpie AGG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomized trial. Lancet 2009;373: Lassen MR, Raskob GE, Gallus A, et al. Apixaban or Enoxaparin for Thromboprophylaxis after Knee Replacement. N Engl J Med 2009;361: Lassen MR, Raskob GE, Gallus A, et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomized double-blind trial. Lancet 2010;375: Eriksson BI, Dahl OE, Rosencher N, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomized, double-blind, non-inferiority trial. Lancet 2007;370: Eriksson BI, Dahl OE, Huo MH, et al. Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II). Thromb Haemost. 2011;105(4): Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Hip Arthroplasty. N Engl J Med 2008;358: Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomized controlled trial. Lancet 2008;372: Lassen MR, Gallus A, Raskob GE, et al. Apixaban versus Enoxaparin for Thromboprophylaxis after Hip Replacement. N Engl J Med 2010;363: The RE-MOBILIZE Writing Committee. Oral Thrombin Inhibitor Dabigatran Etexilate vs North American Enoxaparin Regimen for Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery. J Arthroplasty 2009;24(1): Eriksson BI, Dahl OE, Rosencher N, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007;5: Pollack CV, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015;373: Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 2015;373: Ansell JE, Bakhru SH, Laulicht BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014:371: Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; May 5th, Redbook Online [online database]. Greenwood Village, CO: Truven Health Analytics (accessed 2016 May 5). 5 DECEMBER

6 Learning Assessment Successful completion of A technician s guide to new and old oral anticoagulants ( H01-T) is worth one contact hour of credit. To submit answers, visit our website at NewsCE.com. Please note: Assessment questions submitted online will appear in random order. 1. Which of the following oral anticoagulants would be appropriate for use in a patient who has a mechanical mitral valve? (L/O 1) a) Warfarin b) Dabigatran c) Rivaroxaban 2. Which of the following newer oral anticoagulants currently lacks an indication for prophylaxis of deep vein thrombosis or pulmonary embolism following hip replacement surgery? (L/O 1) 3. Which of the following newer oral anticoagulants is most likely to cause dyspepsia due to its formulation containing a tartaric acid core? (L/O 2) 4. True or false: Bleeding appears to occur in more than 3% of patients with each of the four newer oral anticoagulants. (L/O 2) a. True b. False 5. Based solely off currently available pricing data, which of the following oral anticoagulants is the cheapest option for prevention of stroke or systemic embolism in a patient who has nonvalvular atrial fibrillation? (L/O 3) a) Rivaroxaban b) Apixaban c) Warfarin 6. Which of the following newer oral anticoagulants has a patient-assistance program and/or savings card that can be used in situations where patients are unable to afford the medication? (L/O 3) a) Rivaroxaban b) Apixaban c) Edoxaban d) All of the above 7. Which of the following newer oral anticoagulants is the only pregnancy category B medication amongst this class, and will likely be the preferred selection in this patient population? 8. Which of the following newer oral anticoagulants requires either older age or low body weight to necessitate renal dosage adjustment in a patient who has nonvalvular atrial fibrillation and a serum creatinine of 1.7 mg/dl? 9. True or false: When rivaroxaban is being dosed at 15 mg twice daily for the treatment of DVT/PE, the patient must be instructed to take both 15 mg doses (30 mg) at their earliest convenience, if a dose is missed. a. True b. False True or false: Phytonadione (vitamin K) is an appropriate reversal agent for all of the newer oral anticoagulants. a. True b. False DECEMBER