(B-028) The Association Between Dose and Formulation of Long-term Opioid Therapy and the Risk of Cardiovascular Outcomes in Older Adults

Monday, August 25, 2025

11:30 AM - 1:00 PM ET

Presenting Author(s)

Liang-Yuan Lin

Department of Pharmacy Administration, School of Pharmacy, University of Mississippi, University, MS, USA, United States

Co-Author(s)

KB

Kaustuv Bhattacharya

Department of Pharmacy Administration and Center for Pharmaceutical Marketing & Management, School of Pharmacy, University of Mississippi, University, MS, USA, United States
SB

Shadi Bazzazzadehgan

Department of Pharmacy Administration, School of Pharmacy, University of Mississippi, University, MS, USA, United States
SR

Sujith Ramachandran

Department of Pharmacy Administration, School of Pharmacy, University of Mississippi, University, MS, USA, United States
JB

John P. Bentley

Department of Pharmacy Administration, School of Pharmacy, University of Mississippi, University, MS, USA, United States
YY

Yi Yang

Department of Pharmacy Administration, School of Pharmacy, University of Mississippi, University, MS, USA, United States

Background: Long-term opioid therapy (LTOT) has been associated with an increased risk of cardiovascular diseases. However, research gaps remain regarding the effects of opioid formulation and dosage on these outcomes in older adults with chronic non-cancer pain (CNCP). A better understanding of these associations could inform safer prescribing practices and reduce cardiovascular risks in patients on LTOT.

Objectives: This study aims to assess the relationship between opioid dose and formulation and the risk of cardiovascular outcomes.

Methods: A nested case-control study was conducted using 2012-2020 5% national sample of Medicare claims data. The study cohort consisted of individuals with CNCP aged 65 years or older receiving LTOT. For each cardiovascular outcome of interest—stroke, myocardial infarction (MI), cardiovascular death (and a composite outcome of those three, the 3-point major adverse cardiovascular event [3P-MACE]), heart failure (HF), and arrhythmia—cases were defined as individuals who experienced the specific outcome during follow-up. For each outcome, risk set sampling was used to match cases and controls in a 1:2 ratio based on cohort entry date, baseline disease-risk score— (probability of experiencing each outcome), —and age. Conditional logistic regression models were used to assess the association between opioid dose and formulation with each cardiovascular outcome.

Results: The study cohort included 103,212 individuals, with the majority being female (71.7%) and White (84.7%). The mean age was 76.7 years. Compared to lower opioid doses ( < 20 morphine milligram equivalent [MME]), medium opioid dose (20 – 50 MME) was associated with increased risks of MI (adjusted odds ratio (aOR): 1.12; 95% CI: 1.01–1.23), 3P-MACE (aOR: 1.26; 95% CI: 1.10–1.44), HF (aOR: 1.08; 95% CI: 1.01–1.15), and arrhythmia (aOR: 1.09; 95% CI: 1.03–1.15), and high opioid dose (> 50 MME) was associated with higher risks of MI (aOR: 1.38; 95% CI: 1.20–1.59), 3P-MACE (aOR: 1.51; 95% CI: 1.25–1.83), HF (aOR: 1.21; 95% CI: 1.11–1.33), and arrhythmia (aOR: 1.12; 95% CI: 1.04–1.20). Additionally, using long-acting opioids were associated with an increased risk of arrhythmia (aOR: 1.09; 95% CI: 1.01–1.18) compared to using short-acting opioids alone.

Conclusions: Higher opioid doses and the use of long-acting opioids are associated with an increased risk of adverse cardiovascular outcomes in older adults with CNCP who were receiving LTOT. Our findings highlight the importance of careful opioid prescribing and dose management to mitigate cardiovascular risks in older adults. Further research is needed to develop safe opioid prescribing strategies to reduce cardiovascular risks among older adults with CNCP.