* INR is a blood test to monitor the effect of warfarin. It’s administered after you start treatment. If it varies a lot from test to test, it is considered “labile.” Based on various studies, researchers have found the following progression of annual risk based on the HAS-BLED score.
A score of 3 or above indicates a potential high risk for bleeding and means you’ll probably be monitored more closely, with possible changes in the dose of the anticoagulant you are taking. Blood clotting is critical to the body’s functioning. When you get a cut or wound on your skin, your body works to stop the free flow of blood from the wound. If that didn’t happen you could bleed to death. If a person's blood clots normally, the blood flow slows and eventually stops. Blood can also clot inside your blood vessels, and that is the root many medical problems. Blood clots form when there’s an internal wound or something goes awry with regular and healthy blood circulation. For example, blood can clot in the veins in your legs if you are inactive for a long time, like a long plane ride. Even sitting at a computer for hours can also increase your risk. Doctors call these clots deep vein thrombosis. The symptoms include changes in skin color (redness); leg pain and/or swelling; and skin warm to the touch near the area of the clot. Older people and people with disabilities or those confined to their beds are at high risk of deep vein thrombosis. So are people who’ve had surgery. That’s why doctors routinely prescribe anticoagulants to people who’ve had certain kinds of surgery. The real trouble with blood clots occurs when a clot—wherever it first originates—breaks loose and travels through the blood stream and lodges in a vulnerable place. One place could be the lungs. If a clot travels to the lungs and blocks an artery, it can damage part of the lung and lead to low oxygen levels in the blood; that damages other organs. Such clots are called pulmonary emboli. If untreated, about 30 percent of people who have a pulmonary embolism will die. This condition affects an estimated 400,000 to 600,000 people a year in the U.S. Symptoms of a pulmonary embolism include: sharp or stabbing chest pain under the breastbone or on one side; a burning, aching, or dull, heavy sensation in the chest; shortness of breath. Blood clots are also a serious risk in people diagnosed with atrial fibrillation. In people with AFib, blood can pool in the heart, which can trigger clotting. Such clots can dislodge and lead to damage in any part of the body, including the brain. But by far the worst thing blood clots do—in terms of the number of people affected and the medical impact—is cause heart attacks and strokes. A stroke occurs when a clot blocks the flow of oxygen-rich blood to part of the brain. A heart attack occurs when the flow of oxygen-rich blood to the heart muscle is blocked. In most heart attacks, the event is caused by the formation of a blood clot at the site of a build-up of a waxy substance called plaque on the wall of a heart artery. The clot forms when the plaque ruptures, which occurs suddenly just as with a wound on your skin. If it becomes large enough, the clot blocks the flow of blood and the heart muscle can’t work. Plaque build-up in arteries anywhere in the body is called atherosclerosis. When it occurs in the arteries to the heart muscle, it’s called coronary heart disease. As you have no doubt read or heard, choices in a person's lifestyle (poor diet, no exercise, and smoking) adds to the risk of plaque build-up—and probably plaque rupture—in your arteries. But genetics and family history play an important role, too. All the anticoagulants work well at accomplishing their main task—to substantially lower the risk of stroke in people with AFib. The evidence at this time favors three of the newer drugs over warfarin based on some measures of effectiveness. But there’s broad agreement that evidence is not yet conclusive, and that further studies are needed to better inform doctors and people with AFib about the comparative benefits and risks of the newer drugs compared to warfarin. That’s especially important given that the studies conducted to date were with people usings the newer drugs over 18 to 24 months. However, most people who take anticoagulants will need to take them for the rest of their lives. Warfarin has been conclusively proven to offer sustained effectiveness and benefit over many years of use. In addition, no studies to date compare the newer drugs to each other on effectiveness. Table 4 below presents a summary of the current evidence from the review on which this report is based. It shows that for the recommended doses, dabigatran (Pradaxa) and apixaban (Eliquis) were slightly better than warfarin in preventing strokes. Edoxaban (30 mg dose) was slightly better than warfarin in terms of the overall death rate of patients. Not shown in the table is apixaban (Eliquis), a new drug that has been heavily advertised. It also performed better than aspirin in AFib patients with who had high enough stroke risk to consider warfarin but for other medical reasons could not take it. After 18 months, about 2 percent of patients taking apixaban had a stroke versus almost 5 percent of patients taking aspirin. Additionally, that study found that people who took Eliquis had fewer episodes of bleeding in the brains compared to people taking aspirin. Rivaroxiban (Xarelto) has provided no benefit over warfarin in studies done to date. Table 4. Comparison of newer anticoagulants with warfarin
* Gastrointestinal ** In patients with chronic kidney disease, the FDA-approved dose is half the regular dose. *** The FDA has not approved this lower dose and there is disagreement about whether it could possibly be safer for patients aged 80 and over. **** 2.5 mg twice per day dose recommended for some people, including those over age 80. Source: Stroke Prevention in Atrial Fibrillation—Executive Summary; Agency for Healthcare Research and Quality; Effective Health Care Program; Comparative Effectiveness Review Number 123; August 2013. As shown in Table 4. apixaban (Eliquis) was slightly better than warfarin with respect to its risk of causing major internal bleeding. Notably, only apixaban reduced strokes more than warfarin and was associated with fewer major bleeding episodes than warfarin. As with the evidence for their superior effectiveness compared with warfarin, the evidence on the safety of the newer drugs is still being evaluated and is not yet conclusive. For example, recent analyses by the independent Institute for Safe Medication Practices have found that dabigatran (Pradaxa) is associated with instances of internal bleeding that resulted in more deaths than would have been expected. Pradaxa’s manufacturer, Boehringer Ingelheim, disputes that conclusion and says an analysis of its studies on the drug showed no greater rate of death compared with warfarin when all factors were taken into account. An FDA analysis found that Pradaxa was associated with a slightly lower overall risk of death than warfarin. An analysis by the ISMP also suggests that the 110 mg dose of dabigitran (Pradaxa) may cause fewer bleeding episodes than the 150 mg dose for people 80 and older. The FDA has only approved the 150 mg dose. Based on its studies, Boehringer Ingelheim agrees and would like the lower dose of Pradaxa approved in the U.S. although initial studies presented to the FDA indicated the lower dose was less effective. Signs of internal bleeding caused by anticoagulantsSee a doctor or get medial help right away if you have any of these · Headaches, feeing dizzy or weak · Bleeding that lasts a long time from a cut or wound, or that will not stop · Unusual bleeding from the gums · Nosebleeds, especially if occurring frequently · Heavier-than-normal menstrual or vaginal bleeding · Coughing up blood or blood clots · Vomiting blood or vomit that looks like coffee grounds · Unexpected pain, swelling or joint pain · Red, pink or brown urine · Red or black stools (looks like tar) ConvenienceThe newer anticoagulants have an edge over warfarin on convenience in day-to-day use. The main challenge with warfarin is that getting the dose right for each person requires close attention in the beginning of treatment, and careful monitoring over time. That’s because for some people, how much you body absorbes of the drug can fluctuate. That means the blood can become too thin (higher risk of bleeding) or not thin enough (not good control of clot and stroke risk). In addition, warfarin’s affect can be influenced by other medications and conditions, and even certain foods. Many other commonly used medicines, such as aspirin, can affect warfarin’s action in the body and in turn affect the dose of warfarin a person needs to take. For those reasons, people taking warfarin should be tested frequently—as often as every week—to make sure that their blood levels of the drug are not too high or too low. The test measures blood clotting—specifically a ratio of clotting factors called INR, which stands for International Normalized Ratio. The costs for these visits and tests—depending on how often you need them—could add up and erase some of the savings you’ll achieve by taking the low-cost warfarin. For most people who take warfarin, those obstacles are overcome and the recommended INR can be maintained the majority (up to 70 percent) of the time. Warfarin also takes a week or two to start working. That’s usually fine for people at relatively low risk of stroke. But those at high risk might be given a fast-acting, injectable anticoagulant until warfarin’s effect kicks in. The newer drugs don’t require the INR test. But they do require periodic blood tests to check for anemia, kidney function, and liver function. These tests that are also required periodically for people taking warfarin. Studies are underway now to determine how often those tests need to be done. The main convenience challenge with the newer anticoagulants is stopping them temporarily if you need to have a medical or dental procedure that could cause bleeding. Warfarin poses a similar problem, but is usually dealt with by waiting to have the procedure until the patient’s INR is in the safe range—that is when the anticlotting effect of warfarin has declined. An alternative approach with warfarin is to switch to a fast-acting injectable anticoagulant for a few days before and a few days after a procedure, until warfarin’s effect kicks in again after it’s restarted. This approach is called “bridging.” In contrast, bridging with the newer drugs is not yet well understood, and studies are underway to find the best approach, particularly for people with high CHADVAS scores. The problem is that because the newer drugs achieve a more stable INR, the risk of stroke is presumed to be higher if the drug is stopped temporarily. Our advice: if you do take one of the newer anticoagulant drugs, make sure you carefully assess your risk if you have to stop taking the drug temporarily to have a medical procedure. Taking into account the evidence for effectiveness and safety, as well as cost, we recommend that in most cases, those diagnosed with AFib consider generic warfarin first, making it a Consumer Reports Best Buy drug. It works for most people, has a proven track record, and it’s inexpensive. The evidence that the newer drugs are somewhat more effective than warfarin is not yet conclusive enough to warrant their additional cost—a cost passed on to patients in the form of higher co-payments but which also can contribute to higher insurance premiums. But if you require frequent blood testing while on warfarin, that might understandably push you toward the newer drugs. First, the cost of frequent blood testing can be significant—the tests and the doctor visits that are required. This is especially the case for people who need frequent monitoring. Indeed, the cost of warfarin and related expenses could exceed that of the newer drugs. But if tests are needed only once a month, warfarin’s overall cost would still be less. If you have persistent difficulty achieving a stable level of warfarin in your blood—which usually requires more frequent testing—we recommend that you talk with your doctor about trying one of the newer anticoagulants. If your stroke risk becomes high, you may want to talk to your doctor about whether one of the newer drugs offers advantages over warfarin. One other group of patients may prefer to take the newer drugs: those for whom the inconvenience of warfarin monitoring (even if less frequently) and dietary restrictions will prove a barrier. For example, people who travel a lot could find scheduling visits for testing and monitoring and watching their diet frustrating. Based on the evidence to date, apixiban (Eliquis) appears to be the best initial choice among the newer drugs if you choose to try one (despite the fact that it must be taken twice a day). As noted above, only apixaban reduced strokes more than warfarin and was associated with slightly fewer major bleeding episodes than warfarin. People who have a history of GI problems or take other medicines that pose a risk of stomach bleeding (such as aspirin) should avoid taking dabigatran (Pradaxa). Our evaluation is based on a scientific review of the evidence on the effectiveness, safety, and adverse effects of the oral anticoagulants conducted by the Agency for Healthcare Research and Quality, or AHRQ and published in August 2013. The executive summary of that review is available here. The full report is available at AHRQ’s Effective Healthcare Program. A synopsis of AHRQ’s report written by a medical consultant to Consumer Reports Best Buy Drugs forms the basis of this report. The consultant, at the Oregon Health & Science University’s Drug Effectiveness Review Project, has no financial interest in any pharmaceutical company or product. Additionally, this report was informed by an article that will be published in 2014 in the Journal of the American College of Cardiology. The article—2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation—was sponsored by the American Heart Association, American College of Cardiology, and the Heart Rhythm Society, in collaboration with the Society for Thoracic Surgeons. The prepublication manuscript of the article is available free here. The drug costs we cite were obtained from a health-care information company that tracks the sales of prescription drugs in the U.S. Prices for a drug can vary quite widely, even within a single city or town. The prices in this report are national averages based on sales of prescription drugs in retail outlets. They reflect the “cash” or retail price paid for a month’s supply of each drug in April 2014. Consumer Reports Best Buy Drugs selected the Best Buy Drugs using the following criteria. The drug had to: · Be in the top tier of effectiveness among anticoagulants. · Have a safety and side-effect record equal to or better than other antidepressants. · Have an average price for a 30 day supply that was substantially lower than the most costly anticoagulant meeting the first two criteria. The Consumer Reports Best Buy Drugs methodology is described in more detail in the methods section at www.CRBestBuyDrugs.org. 1. Stroke Prevention in Atrial Fibrillation—Executive Summary; Agency for Healthcare Research and Quality; Effective Health Care Program; Comparative Effectiveness Review Number 123; August 2013. Available at: http://effectivehealthcare.ahrq.gov/ehc/products/352/1669/stroke-atrial-fibrillation-executive-130821.pdf. 2. January, C.T. et al, “2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation,” Journal of the American College of Cardiology (2014), Forthcoming/in press. Full text available at http://content.onlinejacc.org/article.aspx?articleid=1854230. 3. Institute for Safe Medication Practices; Anticoagulant Update; Quarter Watch; May 7, 2014 issue; pages 11-14. 4. The Management of Atrial Fibrillation; Guidelines from the National Institute for Health and Care Excellence (NICE), June 2014. https://www.nice.org.uk/guidance/cg180/resources/guidance-atrial-fibrillation-the-management-of-atrial-fibrillation-pdf 5. Calkins, H, Berger R; Atrial Fibrillation: The Latest Management Strategies; Johns Hopkins University monograph. http://www.johnshopkinshealthalerts.com/special_reports/heart_reports/AtrFibMgmtStrat_landing.html 6. Go AS, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285(18):2370-5. 7. Lloyd-Jones D, et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121(7):e46-e215. 8. Lee WC, et al. Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective. J Med Econ. 2008;11(2):281-98. 9. Thrall G, et al. Quality of life in patients with atrial fibrillation: a systematic review. Am J Med. 2006;119(5):448. e1-19. 10. Stewart S, et al. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow- up of the Renfrew/Paisley study. Am J Med. 2002;113(5):359-64. 11. Dulli DA, et al. Atrial fibrillation is associated with severe acute ischemic stroke. Neuroepidemiology. 2003;22(2):118-23. 12. Paciaroni et al. Atrial fibrillation in patients with first-ever stroke: frequency, antithrombotic treatment before the event and effect on clinical outcome. J Thromb Haemost. 2005;3(6):1218-23. 13. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69(6):546-54. 14. Gage BF, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA. 2001;285(22):2864-70. 15. Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010;137(2):263-72. 16. Pisters R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-100. 17. Camm AJ et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369-429. 18. Ansell J et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):160S-98S. 19. Gitter MJ, Jaeger TM, Petterson TM, et al. Bleeding and thromboembolism during anticoagulant therapy: a population- based study in Rochester, Minnesota. Mayo Clin Proc. 1995;70(8):725-33. PMID: 7630209. 20. Hylek EM, Evans-Molina C, Shea C, et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007;115(21):2689-96. PMID: 17515465. 21. Singer DE et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):546S-92S. 22. Estes et al. ACC/AHA/Physician Consortium 2008 clinical performance measures for adults with nonvalvular atrial fibrillation or atrial flutter: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and the Physician Consortium for Performance Improvement (Writing Committee to Develop Clinical Performance Measures for Atrial Fibrillation): developed in collaboration with the Heart Rhythm Society. Circulation. 2008;117(8):1101-20. 23. Birman-Deych E, et al. Use and effectiveness of warfarin in Medicare beneficiaries with atrial fibrillation. Stroke. 2006;37(4):1070-4. 24. Piccini JP, et al. Quality of care for atrial fibrillation among patients hospitalized for heart failure. J Am Coll Cardiol. 2009;54(14):1280-9. 25. Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. 26. Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. 27. Lopes RD, et al. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010;159(3):331-9. 28. Lip GY, et al. Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis. Europace. 2011;13(5):723-46. 29. Douketis JD, et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):299S-339S. 30. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med. 1997;336(21):1506-11. 31. Siegal D, et al. Periprocedural heparin bridging in patients receiving vitamin K antagonists: systematic review and meta-analysis of bleeding and thromboembolic rates. Circulation. 2012;126(13):1630-9. 32. Spyropoulos AC. Bridging therapy and oral anticoagulation: current and future prospects. Curr Opin Hematol. 2010;17(5): 444-9. 33. Fuster V, et al. 2011 ACCF/AHA/ HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol. 2011;57(11):e101-98. Consumer Reports has no relationship with any advertisers or sponsors on this website. Copyright © 2006-2014 Consumers Union of U.S. |
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