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Objective <p>To examine whether long-term opioid use after total knee arthroplasty (TKA) is associated with subsequent risks of major adverse cardiovascular events (MACE) and all-cause mortality in patients with knee osteoarthritis (OA).</p> Methods <p>This retrospective, population-based cohort study used Taiwan’s Longitudinal Health Insurance Database (LHID) 2005 to identify patients with knee OA undergoing TKA (2002–2018). Opioid exposure was assessed during the 1-year post discharge window (long-term &gt; 3 months vs. non-long-term &lt; 3 months), and the index date was set at 360 days after discharge (landmark design). The primary outcome was first MACE after the index date. After 1:2 propensity score matching (PSM), adjusted hazard ratios (aHRs) were estimated using Cox models; Fine–Gray models were used for nonfatal components.</p> Results <p>In the matched cohort (2,351 long-term vs. 4,702 non-long-term users), long-term opioid use was associated with higher risks of MACE (aHR = 1.16; 95% CI, 1.06–1.26) and all-cause mortality (aHR = 1.16; 95% CI, 1.05–1.29), as well as AMI (aHR = 1.30; 95% CI, 1.03–1.64) and CHF (aHR = 1.15; 95% CI, 1.00–1.32), but not ischemic or hemorrhagic stroke. Effect modification by Charlson Comorbidity Index (CCI) was observed for MACE (P-interaction = 0.0278) and mortality (P-interaction = 0.0006), with the strongest associations in CCI ≥ 5. Time-stratified analyses for MACE showed the excess risk was greatest early after the index date and remained significant through 1–5 years, with attenuation thereafter.</p> Conclusions <p>Long-term opioid use after TKA was associated with increased risks of MACE and mortality, particularly among patients with high comorbidity burden, underscoring the importance of opioid-sparing strategies and closer cardiovascular risk assessment in patients requiring prolonged opioid therapy.</p>

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Association between sustained opioid use and survival or major adverse cardiovascular events after total knee arthroplasty: evidence from a population-based cohort

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月23日

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  • Han-Fang Tseng,
  • Yat-Yin Law,
  • Pei-Ni Chen,
  • Jing-Yang Huang,
  • Chia-Yi Lee,
  • Shun-Fa Yang,
  • Chao-Bin Yeh

摘要

Objective

To examine whether long-term opioid use after total knee arthroplasty (TKA) is associated with subsequent risks of major adverse cardiovascular events (MACE) and all-cause mortality in patients with knee osteoarthritis (OA).

Methods

This retrospective, population-based cohort study used Taiwan’s Longitudinal Health Insurance Database (LHID) 2005 to identify patients with knee OA undergoing TKA (2002–2018). Opioid exposure was assessed during the 1-year post discharge window (long-term > 3 months vs. non-long-term < 3 months), and the index date was set at 360 days after discharge (landmark design). The primary outcome was first MACE after the index date. After 1:2 propensity score matching (PSM), adjusted hazard ratios (aHRs) were estimated using Cox models; Fine–Gray models were used for nonfatal components.

Results

In the matched cohort (2,351 long-term vs. 4,702 non-long-term users), long-term opioid use was associated with higher risks of MACE (aHR = 1.16; 95% CI, 1.06–1.26) and all-cause mortality (aHR = 1.16; 95% CI, 1.05–1.29), as well as AMI (aHR = 1.30; 95% CI, 1.03–1.64) and CHF (aHR = 1.15; 95% CI, 1.00–1.32), but not ischemic or hemorrhagic stroke. Effect modification by Charlson Comorbidity Index (CCI) was observed for MACE (P-interaction = 0.0278) and mortality (P-interaction = 0.0006), with the strongest associations in CCI ≥ 5. Time-stratified analyses for MACE showed the excess risk was greatest early after the index date and remained significant through 1–5 years, with attenuation thereafter.

Conclusions

Long-term opioid use after TKA was associated with increased risks of MACE and mortality, particularly among patients with high comorbidity burden, underscoring the importance of opioid-sparing strategies and closer cardiovascular risk assessment in patients requiring prolonged opioid therapy.