Consequences of Oral Anticoagulant Choice Magnified in the Frail

Derick Alison
Derick Alison
7 Min Read

Older adults with atrial fibrillation (Afib, or AF), especially those with frailty, had better patient-centered outcomes taking apixaban (Eliquis) than other common oral anticoagulants (OACs), Medicare records showed.

Compared with apixaban, rivaroxaban (Xarelto) was associated with significantly increased risk of spending more than 14 days in the hospital or a skilled nursing facility during follow-up of 1 year after initiation (21.9% vs 20.1%, difference 1.8 percentage points, 95% CI 1.5-2.1).

Rivaroxaban also had higher composite risk of ischemic stroke, systemic embolism, major bleeding, or death (rate difference 21.3 more events per 1,000 person-years) and total cost during follow-up of 1 year after initiation (mean difference $890), Kueiyu Joshua Lin, MD, ScD, MPH, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues reported in JAMA Network Open.

Similarly, warfarin versus apixaban use was associated with significantly increased risk of spending more than 14 days in a medical facility (23.3% vs 20.1%) and of combined clinical events (119.5 vs 148.9 events per 1,000 person-years), based on a propensity score-weighted analysis.

In the frail subgroup, apixaban users showed greater relative reductions in home time lost, with a 2.7- and 3.6-percentage-point difference in the frail versus 0.8 and 1.7 percentage points in the non-frail population with rivaroxaban and warfarin, respectively. The differences in composite clinical events for those same comparisons were 31.6 and 45.5 versus 11.6 and 15.1 per 1,000 person-years, respectively.

“Our results support apixaban as the preferred OAC for older adults with AF, particularly for older adults with frailty,” the study authors concluded.

Regardless of frailty, apixaban was associated with a total annual cost lower than rivaroxaban but higher than warfarin (mean difference $1,409), driven by the cost of the OAC itself. After excluding the cost for the OAC, other costs were lowest with apixaban, highest with rivaroxaban, and in between with warfarin.

Apixaban is currently the most commonly prescribed OAC in the U.S.

Although older adults with Afib have been increasingly willing to initiate and adhere to anticoagulant therapy in recent years, oral anticoagulants remain underutilized.

Within the older age group, frail individuals represent a more complex subpopulation that tends to require more rehospitalization and discharge to a location other than home. Notably, this group has traditionally been underrepresented in clinical trials.

“Of note, the results of the study by Lin et al were needed, considering the persisting treatment gaps for AF patients who are frail, the overall underprescription of OAC, and the high risk of adverse outcomes, including thromboembolism,” Bernadette Corica, MD, of Sapienza University of Rome, and colleagues wrote in an accompanying editorial.

Notably absent from the study, however, were comparisons with dabigatran (Pradaxa) and edoxaban (Savaysa), two DOACs less often used in clinical practice.

The study included a nationally representative cohort of Medicare fee-for-service beneficiaries with Afib. All were prescribed OAC therapy due to elevated risk of ischemic stroke, not for another indication such as venous thromboembolism or joint replacement.

Lin’s team relied on prescription claims data to separate apixaban, rivaroxaban, and warfarin users.

After weighting, the study population totaled 136,551 beneficiaries (mean age 77.6 years, nearly 52% women) with balanced baseline characteristics between the three groups. The mean CHA2DS2-VASc score was 4.3.

Frailty, measured using a validated claims-based frailty index, was observed in 23% of the cohort.

“Several factors that may disproportionately affect patients who are frail could explain these results [favoring apixaban], including differential adherence to OACs, drug interactions, and the impact of the prescription of reduced doses of DOACs [direct oral anticoagulants],” Corica’s group wrote.

The editorialists cited some evidence of inappropriate dosing for rivaroxaban but not apixaban in real-world practice.

“Whether and to what extent this issue has contributed to the results observed in the study by Lin et al are unclear, and further studies are needed to analyze the impact of dosing (and particularly, inappropriate dosing) on the efficacy and safety of different DOACs in patients with AF who are frail,” the group wrote.

Lin and colleagues cautioned that unmeasured confounding remained a possibility despite efforts at statistical adjustment in their study. Laboratory test results, use of over-the-counter medications, and other clinical variables were not available in the administrative claims dataset. Finally, the long-term impact of OAC beyond 1 year after initiation was not analyzed in this report, the authors said.

Recently, the FRAIL-AF trial reported that frail older people who were stable on warfarin or other vitamin K antagonists did better staying on it than switching to a DOAC, such as apixaban or rivaroxaban.

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    Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was funded by grants from the National Institute on Aging.

Lin and Corica had no disclosures.

Other study coauthors and co-editorialists reported various ties to industry.

Primary Source

JAMA Network Open

Source Reference: Lin KJ, et al “Frailty, home time, and health care costs in older adults with atrial fibrillation receiving oral anticoagulants” JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2023.42264.

Secondary Source

JAMA Network Open

Source Reference: Corica B, et al “Anticoagulation in patients with atrial fibrillation who are frail — toward better care” JAMA Netw Open 2023; DOI: 10.1001/jamanetworkopen.2023.42258.

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