He pointed out that although a main advantage of the new agents is the lack of requirement for monitoring because they are used at a fixed dose, this also has a flip side. "It means that we don't know if patients are actually taking their drugs," he says. If they are on warfarin we can assess their blood coagulation (blood clotting) levels with a simple blood test, but this is not possible with the new drugs."
He added that this is slightly easier with Pradaxa® than with the factor X inhibitors (Xarelto® and Eliquis®) because Pradaxa® increases clotting time, which can be tested. Whether this correlates with Pradaxa®'s clinical effect is unknown. But there is no test for Xarelto® and Eliquis®. "So while the monitoring of warfarin is a nuisance, it does mean the patient is having regular contact with a medical professional, which helps with adherence." "Patients are at increased risk of an embolic (clotting) event even if they just miss one dose of these new agents. I have personally seen this happen," he said. "This is a big issue, especially as these drugs will be used by a relatively elderly population. Doctors really have to drum this home to their patients. Whereas with warfarin, missing one dose probably wouldn't have much effect." He adds that the cost of the new agents will exacerbate this problem. "These drugs are expensive. I worry that some patients may say they can afford them and start taking them and then decide not to continue because of the cost and not tell their doctor, so put themselves at a large increase in risk of stroke." Dr. Turpie and Dr. Goldstein have different views on the bleeding risks with the new agents and the fact that no antidotes are available as yet. Dr. Turpie says he is "not too worried" about these issues. "The regulatory agencies seem happy with the bleeding data," he said. "It is well known that doctors report side effects more rigorously with new drugs. We see bleeding with warfarin all the time but don't often report it." But Dr. Goldstein believes the lack of an antidote is a problem. "While these drugs effects will wear off relatively quickly, this is not sufficient when a patient is bleeding into the brain or is experiencing another type of life-threatening bleed. You just can't wait for it to stop under those circumstances. " So, having decided that your patient is a good candidate for one of the new agents, how do you to choose which one to go for? On the basis of clinical trial data, all 3 new agents seem to have advantages over warfarin. But they have somewhat different profiles. Dr. Goldstein noted that although all 3 showed a reduction in ICH versus warfarin, Pradaxa® was the only one that actually showed a significant reduction in thrombotic stroke; Eliquis® was the only one that showed a mortality (death) reduction and a reduction in major bleeding. Gastrointestinal bleeding (bleeding in the stomach and intestines) was increased with Pradaxa® and Xarelto® but was not significant with Eliquis®. Other issues that need to be considered include the dosing schedule. Xarelto® has the advantage of a once-daily dose, whereas Pradaxa® and Eliquis® are given twice daily. Dr. Goldstein pointed out that renal insufficiency (decreased kidney funtion) is an issue with all 3 new drugs, and they all need to be modified if kidney function is low, whereas warfarin can be used in patients with renal failure (patients whose kidneys have completely failed). In terms of which drug to select, Dr. Goldstein said, " I think you have to look at all the nuances from the trials and select the drug that is most appropriate for each individual patient. "Things to consider are will they be compliant, will once a day be much more preferable to twice a day, what other drugs are they taking, do they have issues with bleeding or GI [gastrointestinal] problems, and can they pay for the drugs. The doctor needs to have a long conversation with the patient about all these issues before deciding if any of these drugs are suitable and then which one " Dr. Turpie believes all 3 drugs are very similar, and most of the differences seen in the clinical trial results are due to differences in trial design, numbers, and patients recruited rather than the drugs themselves. "I would say that if a patient has renal insufficiency (low kidney function) or is prone to GI side effects, then either Xarelto® or Eliquis® may be a better choice than Pradaxa®."The bottom line is you must have a good discussion with your healthcare practitioner to decide which blood thinner is best for you as an individual patient.