# Trackable, Targeted Anticoagulants for Atrial Fibrillation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $597,486

## Abstract

Atrial fibrillation (AF) is a condition of cardiac arrhythmia with an estimated treatment cost of $6 billion/yr in the
United States (CDC 2016). A serious consequence of AF is increased mortality due to stroke and
thromboembolism; patients with AF are at 2-17 fold increased risk of stroke. Uncoordinated contractions of the
atria results in poor blood flow, creating regions of turbulence or stagnation in the heart that are at risk for
clotting. Thus, antithrombotic therapy is a critical consideration in patient management. Warfarin has been in
use for many years, and more recently new drugs such as rivaroxaban (Xaralto®) have emerged; unfortunately,
these systemically circulating drugs carry risk of major bleeding. Intracranial and intra-abdominal bleeding are
among the dangerous side effects of currently used anticoagulants. Antithrombotic treatment requires careful
balance between managing clotting while not inducing off site bleeding. Because it is believed the 90% of
strokes in AF are due to clots originating from the left atrial appendage, we consider whether targeted delivery
of anticoagulants to the atrium could reduce clotting with less risk of bleeding off site. Inflammation is emerging
as a potential target for delivery of drugs to the atrium in AF because, in AF patients, inflammatory markers
and immune cells are highly elevated in the left atrial appendage. This project proposes to validate sulfated-
dextran-coated, iron oxide nanoparticle (SDIO) anticoagulation agents, which can also be imaged, for targeting
anticoagulant activity to sites of inflammation in the atria in AF animal models. We hypothesize that SDIO will
reduce atrial clotting without increasing systemic blood coagulation time. Preliminary data confirmed that SDIO
could facilitate imaging of activated macrophages in inflamed carotid arteries. In addition, SDIO show
anticoagulant activity in several in vitro assays. In the current work, the ability of SDIO to target inflammation in
the atria will be validated in the thoracic aortic constriction (TAC) mouse model of atrial fibrillation, which
experiences inflammation and clotting in the atria that reflects the human disease. Targeting of SDIO to
inflamed atria will be determined by Magnetic Resonance Imaging (MRI) and Positron Emission Tomography
(PET). The stability of SDIO will be quantified, as a stepping stone to understanding the potential for clinical
translation. Finally the ability to reduce clotting in vivo, and effect on systemic coagulation will be determined in
the thoracic aortic constriction (TAC) model. SDIO represent a class of agents that possesses anticoagulant
activity and also can be imaged. The success of this project would validate a fundamentally different approach
to anticoagulant therapy from Warfarin and other oral anticoagulants, by localizing anticoagulant agents to
sites of inflammation rather than relying on maintaining a circulating dose of drug.

## Key facts

- **NIH application ID:** 9997986
- **Project number:** 5R01HL137887-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** ANGELIQUE Y LOUIE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $597,486
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997986

## Citation

> US National Institutes of Health, RePORTER application 9997986, Trackable, Targeted Anticoagulants for Atrial Fibrillation (5R01HL137887-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9997986. Licensed CC0.

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