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Home , Apixaban

STEPS New Drug Reviews

Apixaban (Eliquis) for Prevention in ROBERT A. BECK, MD, University of Iowa, Carver School of Medicine, Iowa City, Iowa WILLIAM M. KING IV, PharmD, BCPS, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado

STEPS new drug reviews Apixaban (Eliquis) is the third new oral recently labeled to reduce the risk of cover Safety, Tolerability, stroke and systemic in patients with nonvalvular atrial fibrillation. Unlike Effectiveness, Price, and Simplicity. Each indepen- (Coumadin), which indirectly decreases several factors in the extrinsic pathway, apixaban dent review is provided directly inhibits factor Xa, which cleaves prothrombin to yield active .1 by authors who have no Apixaban does not require monitoring of the international normalized ratio. financial association with the drug manufacturer. The series coordinator for Drug Starting dosage Dose form Cost* AFP is Allen F. Shaugh- nessy, PharmD, MMedEd, Apixaban 5 mg twice daily with or without food; 2.5 mg 5- and 2.5-mg tablets $287 Tufts University, Boston, (Eliquis) twice daily in patients with two of the following Mass. characteristics: age ≥ 80 years, body weight < 133 lb (60 kg), or serum creatinine level ≥ 1.5 mg A collection of STEPS pub- per dL (133 µmol per L) lished in AFP is available at http://www.aafp.org/ *—Estimated retail price of one month’s treatment based on information obtained at http://www.goodrx.com afp/steps. (accessed January 29, 2014).

SAFETY Although apixaban has fewer drug inter- Apixaban has a lower risk of than actions than warfarin, coadministration warfarin, but a slightly higher risk of minor with antiplatelet agents, fibrinolytics, hepa- bleeding compared with . One addi- rin, aspirin, and chronic nonsteroidal anti- tional major bleeding episode (defined as inflammatory drugs increases the risk of clinically overt bleeding accompanied bleeding.3 Apixaban has not been studied by a hemoglobin decrease of 2 g per dL in children or in pregnant or [20 g per L] and occurring at a critical site or women and is U.S. Food and Drug Adminis- resulting in death) will be prevented for every tration category B.3 There is no way 66 patients treated with apixaban instead to reverse anticoagulation caused by apixaban. of warfarin over 1.8 years.2 Death from any cause, including death from major bleeding, TOLERABILITY occurs less often with apixaban than with Apixaban is well tolerated. In clinical trials, warfarin treatment (number needed to treat about one in 16 patients (6.3%) discontin- [NNT] = 132 for 1.8 years).2 ued use, primarily for bleeding events (i.e., Discontinuing apixaban therapy places non-major bleeding that led to a physician patients at a greater risk of thrombotic intervention or a change in events. Unless they are discontinuing treat- therapy). Significantly fewer patients taking ment because of serious bleeding, patients apixaban should discontinue therapy com- should be prescribed an alternative anti- pared with those taking warfarin or aspirin. coagulant to prevent an increased risk of Nausea will occur in about 7% of patients stroke.3 taking apixaban.4 ▲

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EFFECTIVENESS 80 years or older, body weight less than Apixaban was compared with aspirin therapy 133 lb (60 kg), or serum creatinine level of in 5,600 patients who had chronic atrial 1.5 mg per dL (133 µmol per L) or more. fibrillation and at least one additional risk There are no known interactions with food. factor for stroke, but for whom warfarin therapy was unsuitable. The likelihood of Bottom Line stroke was lower with apixaban than with Apixaban is at least as effective as aspirin or aspirin (NNT = 50 per 1.1 years; 95% confi- warfarin for preventing in high-risk dence interval, 44 to 84).1 Systemic embolism patients with nonvalvular atrial fibrillation, risk was also lower with apixaban. In addi- especially those who cannot or will not take tion, the annual risk of death from any cause warfarin. It is slightly less likely to cause was not significantly different in patients major bleeding and may have better compli- taking apixaban vs. aspirin. ance because it does not require frequent Apixaban is similarly effective to warfarin laboratory monitoring. However, apixaban for stroke prevention. In a study of 18,201 is significantly more expensive than war- patients with atrial fibrillation or flutter and farin or aspirin, and its anticoagulation at least one additional risk factor for major effect cannot be reversed in the event of an stroke (i.e., based on the CHADS2 stroke emergency. risk prediction tool [congestive , Address correspondence to Robert A. Beck, MD, at hypertension, age 75 years or older, [email protected]. Reprints are not available from the mellitus, and stroke or transient ischemic authors. attack]), there were only small and clinically Author disclosure: No relevant financial affiliations. insignificant differences in the rates of stroke, systemic embolism, and death. Apixaban REFERENCES has not been directly compared with dabiga- 1. Connolly SJ, Eikelboom J, Joyner C, et al. Apixaban tran (Pradaxa) or (Xarelto), two in patients with atrial fibrillation. N Engl J Med. 2011; other recently marketed oral . 364(9):806-817. 2. Granger CB, Alexander JH, McMurray JJ, et al. Apixa- PRICE ban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365 (11):981-992. A one-month supply of apixaban costs 3. Eliquis (apixaban) [package insert]. Princeton, N.J.: approximately $287. Unlike warfarin, apixa- Bristol-Myers Squibb; 2012. http://packageinserts.bms. ban has no associated laboratory monitoring com/pi/pi_eliquis.pdf. Accessed December 31, 2012. costs. 4. Eliquis (apixaban) [package insert]. European Medi- cines Agency. Bristol-Myers Squibb/ EEIG (United Kingdom); 2011. http://www.ema.europa.eu/docs/en_ SIMPLICITY GB/document_library/EPAR_-_Product_Information/ Apixaban is taken orally twice daily. The human/002148/WC500107728.pdf. Accessed Decem- ber 31, 2012. ■ usual dose is 5 mg, reduced to 2.5 mg for patients with any two of the following: age

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