# Supplement to Direct-Acting Oral Anticoagulants: Anticoagulant Activity in Understudied Older NVAF Patients

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $96,900

## Abstract

PROJECT SUMMARY
Direct acting oral anticoagulants (DOACs) are now the anticoagulants of choice for prevention of stroke in
patients with non-valvular atrial fibrillation (NVAF) and are replacing warfarin for treatment of venous
thromboembolic disease. NVAF is a common chronic condition in older adults with the highest prevalence at
ages over 80 years, yet very old adults have been largely excluded from efficacy trials of DOACs. This deficit is
key as very old patients with NVAF differ from younger NVAF patients enrolled in clinical trials as they often
have other chronic conditions treated with multiple medications, have a higher proportion of women than men,
may have reduced renal and hepatic drug clearance, and increased risk of falls and bleeding. We hypothesize
that very old NVAF patients will have higher DOAC concentrations than seen in the clinical trials. We have
preliminary data showing that lower than recommended dosing achieved concentrations similar to
recommended dosing and recommended dosing produced concentrations far in excess of those seen in the
clinical trials for one DOAC (apixaban). We propose to measure rivaroxaban (renal clearance only) and
apixaban (CYP3A4/5 metabolism and renal clearance) factor Xa concentrations in stable NVAF patients over
age 75 receiving these DOACs for clinical indications at doses prescribed by their providers. We will compare
the concentration data to reports from clinical efficacy trials and explore patient level characteristics (such as
age, sex, race, obesity, renal function, clinical conditions, co-medications, frailty), to identify factors associated
with trough and peak concentrations that lie outside ranges expected from clinical trials. If our work confirms
that higher than expected DOAC concentrations are reached in older patients with NVAF, it has both
implications for future research and current clinical care. The work will establish the need for larger definitive
studies assessing clinical outcomes of varying dosing strategies in older patients, and, provide estimates of
potential magnitudes of difference and variability in clinical populations to estimate sample sizes for these
larger definitive studies. The data may also identify potential contributors to underlying mechanism responsible
for clinical subgroup difference on which to base further hypothesis testing. The results may also immediately
impact clinical care of older patients with NVAF that differ from those in randomized trials by suggesting a role
for monitoring factor Xa inhibition or DOAC concentrations during clinical care or when considering dosing
outside of published guidelines.

## Key facts

- **NIH application ID:** 10297780
- **Project number:** 3R21AG067463-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MARGARET C. FANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $96,900
- **Award type:** 3
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10297780

## Citation

> US National Institutes of Health, RePORTER application 10297780, Supplement to Direct-Acting Oral Anticoagulants: Anticoagulant Activity in Understudied Older NVAF Patients (3R21AG067463-02S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10297780. Licensed CC0.

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