More on the New Stroke Prevention Drugs

You may have read the article “Emerging Risks with New Stroke Prevention Drugs” in the April 2013 issue of Worst Pills, Best Pills News. The article discussed the new anticoagulants dabigatran (PRADAXA), rivaroxaban (XARELTO) and apixaban (ELIQUIS). We recommended that patients not use these drugs for seven years after their approval dates, because they do not represent a clear therapeutic breakthrough over the existing drug, warfarin (COUMADIN, JANTOVEN, ATHROMBIN), and it is too early to fully understand the drugs’ risks. The following information is intended both to clarify and correct a few points made in the April 2013 article.

The three new anticoagulants increase the risk of bleeding, but so does warfarin. It is too early to know whether the risk of bleeding with the new drugs is higher, lower or the same as that of warfarin. It also is not possible to predict whether bleeding will be more or less likely to result in death with the new drugs compared to warfarin. While warfarin has an antidote and the new drugs do not, many other factors also can impact whether bleeding turns out to be fatal. Elderly patients and those with kidney or liver problems may be at higher risk of bleeding from the new drugs, because less is known about the correct dosage to give these patients to reduce blood clots that could cause a stroke while avoiding excessive bleeding.

The drug labels of dabigatran and apixaban warn against prescribing these drugs to patients with bioprosthetic and prosthetic heart valves, respectively. Other risks for specific groups are likely to become better understood over the next few years. The drugs are categorized on WorstPills.org as Do Not Use for Seven Years after their approval dates, because better information is needed to avoid and manage their risks.

You should never stop taking a drug without consulting with your doctor first. This is particularly true if you are taking an anticoagulant such as dabigatran, rivaroxaban, apixaban or warfarin. Stopping suddenly could cause a potentially fatal stroke or other injury due to blood clotting. For those taking rivaroxaban or apixaban, there also is a risk of having a rebound stroke if the drug is stopped. Talk to your doctor about ways to reduce this risk by transferring carefully to another anticoagulant.

If you are not taking one of the new anticoagulants, do not start taking them now; ask your doctor about warfarin instead. If you are already taking one of the new anticoagulants, show this article and the April 2013 article to your doctor and have a careful discussion about the risks and potential benefits of staying on your current drug, adjusting its dosage or switching to warfarin.

Corrections to the previous article

The April 2013 article stated that side effects occur more often in patients taking rivaroxaban during hip or knee replacement surgery. The injuries described were blood clots, which are more accurately described as cases in which the drug may not have been effective, as opposed to side effects induced by the drug. Determining what caused the events is challenging. There is no evidence that rivaroxaban is less safe in the context of surgery than in stroke prevention.

The April 2013 article stated that the risks of rivaroxaban may include potential liver damage. Although FDA reviewers were initially concerned about this risk when reviewing the first short-term studies of rivaroxaban, subsequent longer-term studies and post-marketing reports have not shown that rivaroxaban leads to liver damage. However, the drug should not be used in patients with moderate to severe liver impairment or in patients with blood-clotting problems resulting from liver impairment of any severity.

The April 2013 article discussing the new stroke prevention drugs stated that apixaban had not been approved by the Food and Drug Administration (FDA). The drug was approved by the FDA in December 2012.

The April 2013 article stated that rivaroxaban was first approved in July 2011 to treat or prevent recurrence of blood clotting in the legs or main artery of the lung. The original approval only covered prevention of such blood clotting in patients undergoing hip or knee replacement surgery. The indication to treat and prevent recurrence of blood clotting in patients not undergoing surgery was added in November 2012.