# Cardiovascular Risk of Non-Opioid Pain Medications

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

PROJECT SUMMARY
When compared to the general population, U.S. Military Veterans disproportionately experience pain, especially
severe pain. Indeed, pain management is one of the most common reasons Veterans seek medical assistance.
The U.S. Department of Veterans Affairs (VA) and Veterans Health Administration (VHA) have continued to
focus attention on chronic pain management, which has resulted in the implementation of new guidelines and
systems that prioritize non-opioid treatments.
Current pharmacologic alternatives to opioids for chronic pain management include: (1) topical and oral
analgesics such as lidocaine, acetaminophen, and non-steroidal anti-inflammatories (NSAIDs); (2)
antidepressants; (3) anticonvulsants; and (4) muscle relaxants. We and others have defined the cardiovascular
toxicity of NSAIDs and opioid analgesics, but the potential toxicity of other drug classes used to treat chronic
pain remains poorly defined. This is particularly important for three classes of drugs: (1) selective norepinephrine
reuptake inhibitors (SNRIs) antidepressants, (2) antiepileptics, and (3) muscle relaxants. Within each drug class,
duloxetine (SNRI), pregabalin (antiepileptic), and cyclobenzaprine (muscle relaxant) are among the most
frequently prescribed. Usage of these three drugs has generated multiple case reports and raised specific
concerns for increased risk of serious cardiovascular events.
Currently, hundreds of thousands of Veterans are filling prescriptions for these drugs each year, and the use of
non-opioid pain drugs is increasing. Veterans encompass a vulnerable population with high cardiovascular risk
and high rates of chronic pain; thus, they are at higher risk for adverse drug effects. The overwhelming majority
of Veterans with chronic pain do not have cancer or life-threatening illness, which makes the prospect of drug
toxicity from long-term use a particularly important consideration.
Clinical trials play a crucial role in demonstrating treatments' efficacy; however, many drugs have had unforeseen
and serious side effects. Since clinical trials necessarily are limited with regard to generalizability and can be
impractical, pharmacoepidemiologic studies play a critical role in our knowledge about the long-term side effects
of drugs. The proposed pharmacoepidemiologic studies seek to provide critical information about the
cardiovascular risks associated with three widely prescribed non-opioid medications used to treat chronic pain
and frequently prescribed to Veterans in the VA health system. We will use state of the art techniques and a
large database of Veterans to assemble a cohort of patients with chronic non-cancer pain. Aim 1 will define the
risk for serious cardiovascular outcomes in patients taking cyclobenzaprine. Aim 2 will define the risk of serious
cardiovascular events associated with the use of duloxetine. Aim 3 will define the risk of heart failure associated
in patients taking pregabalin. These studies will compare t...

## Key facts

- **NIH application ID:** 9780917
- **Project number:** 1I01CX001741-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Cecilia Pilar Chung
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9780917

## Citation

> US National Institutes of Health, RePORTER application 9780917, Cardiovascular Risk of Non-Opioid Pain Medications (1I01CX001741-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9780917. Licensed CC0.

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