Vitamin K inhibitors
Vitamin K inhibitors interfere with the cyclic interconversion of vitamin K, thereby inhibiting factors II, VII, IX, and X (procoagulants), as well as impairing proteins C and S, which are natural inhibitors of coagulation.18,19 Before the development of new oral anticoagulants (NOACs) that are not vitamin K antagonists, warfarin was the only available oral anticoagulant option.20 Despite the availability of NOACs, use of warfarin for thromboembolic prevention in patients with nonvalvular AF continues to be prevalent worldwide.21
Warfarin levels are monitored by prothrombin times (PTs) and international normalized ratios (INRs). Ideal INR levels for patients with nonvalvular AF should be maintained between 2.0 and 3.0 (Table 1).22 INR level should be checked 2 to 3 days after initiation of treatment and should continue every 2 to 3 days until two consecutive INR checks fall within therapeutic range.23 Once this occurs the clinician may check the INR once every week until another two consecutive INR checks fall within therapeutic range.23 At this point, clinicians may then check INR levels once every 2 weeks until two consecutive INR checks fall within therapeutic range and then reduce to once every 4 weeks for continued monitoring.23 Any INR level that falls below 2.0 results in increased thrombosis risk, whereas any INR level that rises above 4.0 increases risk of serious bleeding.22
Warfarin can cause several adverse effects, but bleeding is the most serious. Clinicians should be prudent in assessing a patient’s risk for bleeding prior to prescribing warfarin. Many tools are available to assess a patient’s risk of bleeding; however, the HAS-BLED (Hypertension, Abnormal renal or liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly) tool has demonstrated more efficiency in predicting bleeding risk.24 Use of the HAS-BLED score requires the clinician to assign 1 point for each risk factor described by the acronym.24 Scores of 3 or higher indicate an increased risk of bleeding, and clinicians should make every attempt to modify risk factors prior to beginning therapy in these patients.24 Should a patient on warfarin have serious bleeding, packed erythrocytes and fresh frozen plasma may be needed to stabilize the patient immediately.25 Vitamin K1 should also be given because it is the only effective antidote, but anticoagulation reversal may take several hours.25
For patients who are scheduled for surgery, warfarin therapy should be discontinued 5 to 6 days before the procedure.26 In patients who are at high risk for developing blood clots, the clinician may consider the use of bridge therapy. In bridge therapy, patients are usually prescribed a low–molecular-weight heparin starting 3 days before surgery with the last of these doses ending 24 hours before the procedure and beginning again 24 hours or more after surgery for 4 to 6 days; it is given concomitantly with warfarin until therapeutic levels of warfarin have been reached.26
Additional considerations in warfarin therapy include dietary intake, use of dietary supplements, and use of certain antibiotics. Patients should be made aware of foods rich in vitamin K and be informed that they may decrease the effect of warfarin.27 Rather than avoid these foods, patients should be advised not to make any drastic changes in current dietary habits, especially those that involve foods rich in vitamin K.27 Several dietary supplements, including ginger, gingko, St. John’s Wort, and vitamin E, can affect PT and INR levels, and potentially increase a patient’s risk of bleeding.27 The safest policy is to advise patients to avoid supplements unless they are absolutely necessary.27 Some antibiotics may interfere with the pharmacodynamics of warfarin; thus, clinicians should always be aware of a patient’s current medications.27
Although there are several medications available for nonvalvular AF, treatment should be tailored to the individual. The clinician should take into consideration a patient’s risk for bleeding and stroke and current medication regimen prior to prescribing any anticoagulant. Important socioeconomic factors, including a patient’s ability to pay for certain medications, a patient’s ability to adhere to potentially complicated medication regimens, and/or individual patient preference, should also be taken into consideration when prescribing anticoagulant therapy. The number of individuals with nonvalvular AF is growing, and clinicians should make every effort to be familiar with the benefits and challenges of available treatments.
Christy McDonald Lenahan, DNP, MSN, FNP-BC, and Deedra Harrington, DNP, MSN, APRN, ACNP-BC, are assistant professors with the College of Nursing and Allied Health Professions of the University of Louisiana at Lafayette.
- Go AS, Mozaffarian D, Roger VL, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28-e292.
- Colilla S, Crow A, Petkun W, et al. Estimates of current and future incidence and prevalence of atrial fibrillation in the US adult population. Am J Cardiol. 2013;112(8):1142-1147.
- January CT, Wann LS, Alpert JS, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-e76.
- Berry E, Padgett H. Management of patients with atrial fibrillation: diagnosis and treatment. Nurs Stand. 2012;26(22):47-56.
- Lehne RA. Anticoagulant, antiplatelet, and thrombolytic drugs. In: Lehne RA, ed. Pharmacology for Nursing Care. 8th ed. St. Louis, MO: Elsevier Saunders; 2013:631-661.
- Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2011.
- Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2012.
- Savaysa [package insert]. Parsippany, NJ: Daiichi Sankyo, Inc.; 2015.
- Douketis JD, Spyropoulos AC, Spencer FA, et al; American College of Chest Physicians. Perioperative management of antithrombotic therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e326S-e350S.
- Ageno W, Gallus AS, Wittkowsky A, et al; American College of Chest Physicians. Oral anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e44S-e88S.
- Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation. 2011;123(13):1436-1450.
- FDA approves Pradaxa, marking a major milestone to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. Boehringer-Ingelheim website. http://us.boehringer-ingelheim.com/news_events/press_releases/press_release_archive/2010/october_20_2010.html. Published October 19, 2010.
- Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2010.
- Lee CJ, Ansell JE. Direct thrombin inhibitors. Br J Clin Pharmacol. 2011;72(4):581-592.
- Boehringer Ingelheim submits applications for approval of idarucizumab*, specific reversal agent to dabigatran etexilate (Pradaxa®), to EMA, FDA and Health Canada. Boehringer-Ingelheim website. https://www.boehringer-ingelheim.com/news/news_releases/press_releases/2015/03_march_2015_dabigatranetexilate.html. Published March 3, 2015.
- Pradaxa. Drugwatch website. http://www.drugwatch.com/pradaxa. Updated October 16, 2015.
- Phend C. Monitoring, dose adjustment for Pradaxa. MedPage Today website. http://www.medpagetoday.com/Cardiology/Arrhythmias/46901. Published July 23, 2014.
- Hirsh J, Fuster V, Ansell J, et al. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation. 2003;107(12):1692-1711.
- Hull RD, Garcia DA. Therapeutic use of warfarin and other vitamin K antagonists. UpToDate website. http://www.uptodate.com/contents/therapeutic-use-of-warfarin-and-other-vitamin-k-antagonists. Updated November 17, 2015.
- Wigle P, Hein B, Bloomfield HE, et al. Updated guidelines in outpatient anticoagulation. Am Fam Physician. 2013;87(8):556-566.
- Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172(8):623-631.
- Warfarin. CARE Clinical Research website. https://www.careinternet.net/caregiver/warfarin.php. Updated May 20, 2015.
- Warfarin management CPG—ambulatory appendix A: warfarin management dosing tool—adult—ambulatory. UWHealth website. http://www.uwhealth.org/files/uwhealth/docs/pdf3/Warfarin_Dosing_Protocol.pdf. Published April 17, 2014.
- Lane DA, Lip GY. Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation. 2012;126(7):860-865.
- Olson KR. Warfarin and superwarfarin toxicity medication. Medscape website. http://emedicine.medscape.com/article/821038-medication. Updated December 10, 2014.
- BRIDGE Study Investigators. Bridging anticoagulation: is it needed when warfarin is interrupted around the time of a surgery or procedure? Circulation. 2012;125(12):e496-e498.
- Important information to know when you are taking: warfarin (coumadin) and vitamin K. National Institutes of Health website. http://www.cc.nih.gov/ccc/patient_education/drug_nutrient/coumadin1.pdf. Published September 5, 2012.
All electronic documents accessed January 7, 2016.