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

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $161,500

## Abstract

PROJECT SUMMARY / ABSTRACT
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 adults over age 55 with a
lifetime risk of 37% and the highest prevalence at ages over 80 years. Yet, adults over 75-80 years of
age have been under-represented in trials of DOACs. This deficit is key as many older adults with
NVAF differ from younger adults with NVAF enrolled in clinical trials. Older NVAF patients often have
multiple chronic conditions, reduced renal and hepatic drug clearance, receive multiple medications,
have increased risks for falls and bleeding, and may include more women than men. We hypothesize
that older adults with NVAF encountered clinically will have higher DOAC concentrations than
expected from clinical trials. Our preliminary data shows higher than expected concentrations of the
DOAC apixaban with under-dosing, and concentrations far in excess of those in clinical trials with
recommended dosing. We propose to measure factor Xa-calibrated concentrations of rivaroxaban
(renal clearance only) and apixaban (CYP3A4/5 metabolism and renal clearance) in medically stable
adults over age 75 with NVAF receiving these DOACs for clinical indications at doses prescribed by
providers. We will compare these concentration data to those from clinical trials and explore patient
level characteristics (such as age, renal function, co-medications), associated with concentrations
(peak and trough) that lie outside ranges expected from clinical trials. If the work determines that older
adults with NVAF encountered clinically have different concentration responses to DOAC dosing
compared to clinical trials, it will establish the need for further investigations to optimize DOAC efficacy
and safety in older adults with NVAF, may identify unrecognized factors associated with high DOAC
concentrations, and may support a role for monitoring DOAC concentrations in selected patients. If
the work fails to detect different concentration responses to DOAC dosing in older adults with NVAF, it
will support initiatives to reduce the current prevalence of lower than recommended DOAC dosing

## Key facts

- **NIH application ID:** 10141176
- **Project number:** 5R21AG067463-02
- **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:** $161,500
- **Award type:** 5
- **Project period:** 2020-04-15 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141176

## Citation

> US National Institutes of Health, RePORTER application 10141176, Direct-Acting Oral Anticoagulants: Anticoagulant Activity in Understudied Older NVAF Patients (5R21AG067463-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141176. Licensed CC0.

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