Case Study: Deciding Appropriate DOAC Treatment for Older Adult With New Onset Atrial Fibrillation

For older adults on dialysis, there are some important considerations to take into account when choosing between apixaban (Eliquis; Bristol-Myers Squibb Company) and warfarin (Coumadin; Bristol-Myers Squibb Company) for anticoagulation treatment, explained Stephanie Sibicky, PharmD, MEd, BCGP, BCPS, FASCP, during a session at the American Society of Consultant Pharmacists (ASCP) 2022 Annual Meeting.

To make a decision regarding treatment of either apixaban or warfarin for an older adult patient coming in for new onset atrial fibrillation, Sibicky explained that it is important to first assess the patient’s medical history. In the case of a female patient referred to as Helen, who is 64 years of age, her past medical history includes type 1 diabetes (T1D), end-stage renal disease on hemodialysis, anemia, chronic kidney disease, and hypertension. After looking at her history, Sibicky noted that CHA2DS2-VASc score is 4, and her HAS-BLED score is 3, so she meets criteria to explore both apixaban and warfarin as anticoagulation treatment options.

“She also is meeting the thresholds for the HAS-BLED score, so we really started thinking about, ‘What is her bleeding risk because she's starting to get into that more worrisome territory,’” Sibicky said.

Additionally, Sibicky explained that when looking at her comorbidity burden, atrial fibrillation and end-stage renal disease in patients who are on hemodialysis is fairly common.

“It's about 15% to 40% of patients who are receiving renal replacement therapy have atrial fibrillation,” Sibicky said. “There's a thought that patients who are undergoing dialysis or who have end-stage renal disease have this higher propensity for thromboembolic events, and it's been shown in several observational studies that that is the case.”

Sibicky noted that there is also an increased risk for intracranial and gastrointestinal bleeding in patients with atrial fibrillation, mostly because patients who have atrial fibrillation are on anticoagulation.

“Then there's other theories that go into this, like patients who go for dialysis are often exposed to heparin (Heparin Sodium Injection, USP; Pfizer), they have more friable vasculature,” Sibicky said. “So there's lots of risk factors that really overlap between end-stage renal disease as well as atrial fibrillation that we need to consider.”

In assessing the case for treating Helen with warfarin, Sibicky explained that an advantage is the wealth of experience health care professionals have in using warfarin, despite there not being a significant amount of published data regarding its use in this population.

“We know that warfarin is mostly hepatically metabolized. So just off the bat, thinking pharmacokinetically, we can say warfarin might be a better option because we're not even involving the kidney all that much,” Sibicky said. “The current atrial fibrillation guidelines also state, ‘It might be reasonable to use warfarin in patients dependent on dialysis.”

Another thing that is important to consider around treating Helen with warfarin is the readily available reversal agent.

“If we are worried about bleeding, we do have vitamin K fairly easily accessible,” Sibicky said.

However, there remain significant concerns for treating Helen with warfarin due to bleeding and clotting risks.

“We do have to monitor still, and we have to think about [international normalized ratio (INR)],” Sibicky said. “So we're going to be using the 2 to 3 range, but that time within therapeutic range (TTR) is actually still important.”

In studies for this patient population, Sibicky noted that TTR is fairly inconsistent, often ranging between 30% and 50%.

“Which is not great,” Sibicky said. “And low TTR is associated with worse outcomes, which then is compounded on worse outcomes when someone has reduced renal function. So remember, those risk factors are really overlapping each other, so we have to be really careful about that.”

The goal is to have TTR at least above 50%, Sibicky explained; however, she noted that optimally, TTR would be greater than 70%.

On the other hand, in the case for treating Helen with apixaban instead of warfarin, Elizabeth Pogge, PharmD, MPH, BCGP, BCPS, FASCP, FAzPA, a co-presenter during the ASCP session, explained that apixaban has approximately 27% renal clearance. Pogge noted low renal clearance would make it ideal for this patient population.

Additionally, Pogge explained that data pulled from a 2018 Medicare cohort showed that apixaban use is on the rise, with approximately 56% of patients with atrial fibrillation on end-stage hemodialysis given apixaban as compared to warfarin.

“So this agent is emerging and is getting utilized a lot more in this patient population,” Pogge said. “There are some newer data that show that apixaban is safe in this population, and perhaps even better than warfarin.”

Pogge explained further that in a meta-analysis of 16 observational studies, 2 of the trials included direct oral anticoagulants (DOACs). When looking at efficacy, Pogge noted that the only DOAC that had efficacy information is apixaban.

“In my opinion, I think [apixaban] is the best anticoagulation to use in patients that are on hemodialysis,” Pogge said. “In terms of stroke or systemic embolism—which is what we care about when we use anticoagulation—there was no difference between any of the groups.”

Additionally, Pogge noted that when you look at the comparison group, apixaban at 5 milligrams as compared to warfarin had decreased rates of mortality in the apixaban group. Also, apixaban at 5 milligrams as compared to 2.5 milligrams had decreased rates of mortality, whereas apixaban at 5 milligrams versus no oral anticoagulation had decreased mortality as well.

“So in our patient population—our older adults—we'd like to prevent mortality, as well as major bleeding. Apixaban is also superior in terms of major bleeding,” Pogge said. “So it makes sense that we would want to put our patients on apixaban to reduce mortality as well as to reduce major bleeding.”

Reference

Pogge E, Sibicky S. On the Bleeding Edge: Debating the Use of Anticoagulants in Older Adults. Presented at: American Society of Consultant Pharmacists (ASCP) 2022 Annual Meeting in San Antonio, TX; November 6, 2022.