No significant relationships between cancer and stroke, systemic embolism, ischemic stroke, or death could be determined, and the relationship between cancer and myocardial infarction was not significant after statistical adjustment. Apixaban was associated with improved rates of the composite endpoint stroke, systemic embolism, myocardial infarction, and mortality in those with active cancer and in those without cancer but not in those with remote cancer [ 50 ].
Apixaban was deemed to be more effective than warfarin in AF patients on polypharmacy compared to warfarin and at least equivalent in terms of safety. The safety and effectiveness of apixaban in this subpopulation was consistent with the larger study results, that is, apixaban may be an appropriate choice for a patient with valve replacement or repair [ 52 ].
Using data from this study, it was found that For the primary outcome endpoint stroke or systemic embolism , both apixaban and warfarin were similar, and interacting medications had no effect on this outcome [ 53 ]. Using a Markov model and a population model from to , apixaban was compared to warfarin in the German population of nonvalvular AF patients. The study showed that apixaban use instead of a VKA could avoid 52, major clinical events, including 14, all-cause deaths and 15, nonfatal strokes [ 55 ].
Dabigatran, a prodrug, is a direct thrombin inhibitor with predictable pharmacokinetics and pharmacodynamics, no need for laboratory monitoring, and fewer drug-food and drug-drug interactions compared to VKA. Unlike other NOAC drugs, dabigatran has an approved specific reversal agent, idarucizumab [ 57 ].
For dabigatran mg twice daily, the rate of stroke or systemic embolic events was significantly lower than that of patients taking warfarin, but for those on mg twice daily, rates were similar to warfarin.
Intracranial bleed rates and mortality rates were significantly lower in both dabigatran groups compared to warfarin regardless of whether or not the patient had valvular heart disease [ 59 ]. The randomized phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement RE-ALIGN study was terminated early when it compared VKA therapy to dabigatran and the dabigatran group experienced a high rate of thromboembolic and bleeding adverse events [ 60 ].
The reasons for this have been speculated: dabigatran doses were too high, dabigatran was introduced too soon after valve surgery, or there remain factors to be elucidated about thromboembolic risks associated with artificial heart valves [ 62 ]. Edoxaban, a factor Xa inhibitor, is approved for the prevention of stroke in nonvalvular AF patients. Factor Xa is a protease that serves to convert prothrombin into thrombin which, in turn, converts fibrinogen into fibrin and allows for clotting.
Edoxaban has a dual mechanism of action in that it inhibits both free Factor Xa and also the by-product Factor Xa produced by prothrombinase [ 63 ]. Like other NOAC medications, it requires less laboratory monitoring, has fewer drug-drug and food-drug interactions, and lowers the risk of major bleeding compared to warfarin. It is an oral agent that need be taken only once daily [ 63 ]. The safety and efficacy of edoxaban seem to be similar to other NOAC medications for the control of venous thromboembolism to reduce the risk of stroke in nonvalvular AF patients.
Valvular heart disease is associated with an increased risk for major adverse cardiovascular events, major bleeding, and death. Higher-dose edoxaban was found to be similarly effective to warfarin for all endpoints stroke, systemic embolic event, major bleeding in a trial of 18, patients [ 64 ].
As such, edoxaban may be preferred over warfarin in elderly patients at risk for falls [ 66 ]. It does not require laboratory monitoring and has predictable pharmacokinetics and pharmacodynamics and relatively few drug-drug and drug-food interactions compared to warfarin [ 67 ].
There is currently no approved reversal agent for rivaroxaban. The composite safety endpoint was major bleeding or major bleeding plus clinically relevant non-major bleeding and occurred at a rate of The study concluded that rivaroxaban was noninferior to warfarin in prevention of stroke and systemic embolism. There was no significant difference in major or non-major but clinically relevant bleeding between rivaroxaban and warfarin.
Gastrointestinal bleeding occurred more often in rivaroxaban than warfarin patients, but rates of major bleeding were similar. There may be cases when it becomes necessary to change from warfarin to an NOAC or vice versa. The association between AF and dementia is not well elucidated, but white matter lesions, silent brain infarcts, and microbleeds in the brain are more common in AF patients, and it is not clear whether anticoagulation might play a role in this decreased risk for dementia [ 71 ].
Patients with liver disease are at risk for increased bleeding with anticoagulation therapy but not increased thromboembolic events [ 72 ]. Warfarin is teratogenic and should not be administered to pregnant women or women of childbearing potential without a clear understanding that they must not get pregnant while taking this drug [ 74 ].
NOAC anticoagulation offers advantages over VKA anticoagulation but also poses new challenges in the management of emergency situations. Emergency thrombolysis for treatment of ischemic stroke requires that the coagulation system be intact and, for this reason, is contraindicated in patients taking NOAC drugs, unless the agent is completely reversed before [ 75 ]. For major bleeding events, rapid reversal of anticoagulation may be required which is likewise easier with VKA; however, reversing VKA agents such as warfarin may still take hours.
The NOAC medications and warfarin have been the subject of large published clinical trials, but head-to-head studies among the NOACs have not yet been carried out, and attempts to analyze data across trials have been challenged by differences in study methodologies, the AF populations evaluated, definitions stroke, AF, major bleeding, and so on , and composite endpoints [ 76 ].
Compared to dabigatran, rivaroxaban had similar risks for stroke and systemic thromboembolism and myocardial infarction, but the risks for major bleeding, gastrointestinal bleeding, and all-cause mortality were higher with rivaroxaban than dabigatran [ 77 ]. A retrospective study found that rivaroxaban and apixaban elevate the INR to levels above the high cutoff for normal A retrospective study of geriatric patients with head trauma found that NOAC therapy was a safer alternative than warfarin, although warfarin and NOACs were associated with similar mortality rates.
NOAC patients had a lower rate of intracranial hemorrhage progression [ 79 ]. A retrospective database study of nonvalvular AF patients newly started on rivaroxaban, apixaban, or warfarin matched 11, rivaroxaban users to 11, warfarin patients and reported that the risk of ischemic stroke or intracranial hemorrhage was significantly lower in the rivaroxaban patients than in the warfarin patients.
The study further matched apixaban patients to warfarin patients and found the combined endpoint ischemic stroke or intracranial hemorrhage was nonsignificantly reduced by apixaban versus warfarin. Apixaban reduced the risk of intracranial hemorrhage hazard ratio 0. The study did not compare rivaroxaban to apixaban [ 80 ]. After 1 year of follow-up from TAVR, the composite endpoint occurred in In a systematic review of anticoagulation therapy in AF patients with valvular heart disease and bioprosthetic heart valves, edoxaban 30 mg was associated with the least rate of major bleeding compared to rivaroxaban, VKA, and other similar agents.
Overall, NOAC medications were more effective in this population than warfarin, and NOACs were similar with the exception of edoxaban and major bleeding rates [ 82 ]. Evidence from clinical trials shows promise but does not yet provide clinicians with a complete picture.
For example, patients with moderate to severe mitral stenosis or those with a mechanical heart valve are both at elevated risk from thromboembolism and typically excluded from head-to-head clinical trials that compare VKAs to specific NOACs.
Patients with AF and a mechanical heart valve are routinely excluded from most head-to-head trials on anticoagulation. Thus, there are gaps in the evidence as to which types of anticoagulation treatments are most effective in specific populations. Although it is well known that anticoagulation therapy can help prevent stroke in AF patients at risk for thromboembolic events, only about half of the indicated patients actually are prescribed with therapy [ 83 ].
There is an inverse relationship between antiplatelet prescription and non-prescription of anticoagulation therapy. However, antiplatelet therapy is not as effective as anticoagulation medications for stroke prevention [ 84 ]. When prescribing anticoagulation therapy, the clinician must evaluate several factors: the indications for anticoagulation therapy, individual patient characteristics, whether or not the patient is taking other medications, patient preferences if any , clinician and institutional preferences, and cost [ 14 ].
When antiplatelet therapy is combined with anticoagulation, the risk for bleeding increases [ 14 ]. Although some large trials of NOACs have included such patients, there have been no specific studies to investigate the safety of such drugs in these populations [ 85 ], and there is little evidence to guide prescribing choices. Comorbidities must be considered when selecting the optimal anticoagulation regimen for a specific patient.
A retrospective database study from Korea 12, warfarin patients and 24, NOAC patients found NOACs reduced the risk for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, and all-cause death compared to warfarin. Renal failure, common in AF patients, has an inflammatory pathophysiology and puts patients at risk for both thromboembolitic events and bleeding [ 87 ]. About 6 out of 1, people who take a DOAC may have bleeding in the brain.
When you take warfarin, you'll need to get regular blood tests to make sure you are taking the right dose. And you will need to watch how much vitamin K you eat and drink. When you take a DOAC, you don't need to have regular blood tests to check if you are taking the right dose and you don't need to watch your vitamin K intake. Warfarin usually costs less than DOACs. Warfarin is available as a generic medicine. Generic medicines cost less than brand-name medicines. Some or all of this cost may be covered by your provincial health plan or private health insurance plan.
If you have a bleeding problem or need surgery right away, your doctor may need to quickly reverse the effects of an anticoagulant.
Dabigatran and warfarin. Doctors can use medicines to quickly reverse the effects of these anticoagulants and stop bleeding. Apixaban, edoxaban, and rivaroxaban. Doctors do not have a medicine that has been proven to quickly reverse the effects of these anticoagulants. These stories are based on information gathered from health professionals and consumers.
They may be helpful as you make important health decisions. I live on a ranch more than kilometres from my doctor's office. I don't plan on checking in with him every month to have my blood tested.
So I'm going to try a blood thinner that doesn't need regular blood testing. I've been taking warfarin for a long time. I guess I'm just used to it. I haven't had any problems with it. I think I'll just keep taking it. The high cost of medicines is a concern. But I'd rather pay more and not have to watch what I eat or go to the doctor so often.
I like knowing that my doctor is checking my blood regularly. I think I'll try warfarin first and see how it works. Your personal feelings are just as important as the medical facts. Think about what matters most to you in this decision, and show how you feel about the following statements. I'd rather take a familiar medicine with a long record of use, like warfarin. Now that you've thought about the facts and your feelings, you may have a general idea of where you stand on this decision.
Show which way you are leaning right now. How sure do you feel right now about your decision? Use the following space to list questions, concerns, and next steps. Here's a record of your answers. You can use it to talk with your doctor or loved ones about your decision. Do I need to have regular blood tests to check the medicine dose if I'm taking a direct oral anticoagulant DOAC apixaban, dabigatran, edoxaban, or rivaroxaban?
Are you clear about which benefits and side effects matter most to you? Do you have enough support and advice from others to make a choice?
Author: Healthwise Staff. Medical Review: Rakesh K. This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content. To learn more about Healthwise, visit Healthwise. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.
Get the facts. Your options Take warfarin to prevent stroke. Take a direct oral anticoagulant DOAC to prevent stroke. Key points to remember Atrial fibrillation increases your risk of stroke. Your doctor can help you understand which medicine might be best for you.
This may depend on your health and your preferences about taking medicine. Warfarin has been used for many years to reduce the risk of stroke in people with atrial fibrillation. The medicine is low-cost. Newer anticoagulants, called direct oral anticoagulants DOACs , also lower the risk of stroke.
These medicines are apixaban, dabigatran, edoxaban, and rivaroxaban. They work as well as or slightly better than warfarin. But DOACs usually cost more than warfarin. A DOAC may be a good choice if you prefer these medicines. If significant bleeding occurs in a patient taking warfarin, there is a reversal agent —vitamin K.
Pradaxa, Xarelto, and Eliquis, in contrast, have no antidote. We have been asked if FDA should approve anticoagulant drugs that do not have a reversal agent. The approval of each of these drugs was based on a large clinical trial where the rates of strokes and bleeding were carefully monitored and compared. Despite the lack of availability of reversal agents for the new drugs, and the fact that they were being compared with warfarin, a drug that did have a reversal agent, they caused no more bleeding than warfarin, and one drug caused less Eliquis.
Two of the drugs Pradaxa and Eliquis were superior to warfarin in preventing strokes and other important blood clots, and Xarelto was very similar to warfarin. As noted above, all three drugs caused fewer intra-cranial hemorrhages than warfarin.
For these reasons, it was clear that these drugs were worthy of approval, even in the absence of a reversal agent. We recognize, however, that patients with severe, life-threatening bleeding require immediate therapy, and such patients might benefit from a reversal agent if one were available. There is much interest in developing such agents. It is important to understand, however, that most of the bleeding associated with anticoagulants is not life-threatening; in fact, fatal bleeding is quite rare.
Fortunately, DOACs are known to have less incidence of intracranial bleeding and fewer incidents of hematoma than warfarin. Although the DOAC mechanisms responsible for reduced intracranial bleeding compared to warfarin have been investigated in animal experiments, they have not yet been fully elucidated.
To clarify these mechanisms, researchers from Kumamoto University, Japan used a Total Thrombus-Formation Analysis System T-TAS to analyze on- and off-treatment blood samples from patients who underwent catheter ablation for atrial fibrillation and who were taking warfarin or DOACs. The T-TAS is a device that can monitor thrombus formation by using a microchip mimicking blood vessels, a pump that circulates collected blood, a pressure sensor, and a video microscope.
The characteristic features of this device are that it only requires a small blood sample volume ? L for analysis and that collected blood can be measured easily without any complicated pretreatment. With the T-TAS, it is possible to observe the thrombus formation as the blood flows into the obstructed-blood-vessel microchip model, and quantitatively evaluate the speed and volume of thrombus formation.
Twenty-nine patients were treated with warfarin, 19 with dabigatran, 47 with rivaroxaban, and 25 with apixaban; the latter three being DOACs. The T-TAS analysis showed that the level of anticoagulation for patients on-treatment decreased by the same degree in all groups compared to those off-treatment, indicating that all of the anticoagulants were working sufficiently. However, when observing thrombus formation over time with a microscope, the researchers found that thrombi adhering to the wall of the obstructed-blood-vessel microchip thickened earlier in the rivaroxaban and apixaban groups compared to those in the warfarin group.
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