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Purpose <p>Current research on potentially clinically significant drug-drug interactions (DDIs) in individuals with atrial fibrillation (AF) has predominantly focused on DDIs involving direct oral anticoagulants (DOACs), with limited evidence regarding other medications. Our study aimed to: (i) assess the overall prevalence of DDIs; (ii) investigate potential demographic correlates of DDIs; and (iii) examine the association of DDIs with adverse clinical outcomes in a nationwide cohort of older adults with AF and multimorbidity.</p> Methodology <p>Data from the Swedish national registers were linked to establish a cohort with a 2-year follow-up of adults ≥ 65 years who, on 1 January 2017, had a diagnosis of AF, ≥ 1 comorbidity and were prescribed ≥ 2 medications (<i>n</i> = 192,716). This study describes the prevalence of 72 potentially clinically significant DDIs from an adapted explicit international consensus list and a review focused specifically on DDIs involving DOACs. Correlates of DDIs were assessed through logistic regressions. Cox regression analyses were conducted to examine the association between DDIs and adverse clinical outcomes: overall and cardiovascular (CV) mortality, overall and CV hospitalisation, stroke, bleeding, and falls.</p> Results <p>In the overall population, 37.5% presented with ≥ 1 potential DDI, with CV (33.8%) and central nervous system (CNS) drugs (12.4%) most frequently involved. Sex, age, and civil status were most consistently associated with DDIs. Individuals with ≥ 1 DDI had a higher hazard of CV death (hazard ratio 1.28 95% confidence interval (CI) [1.24–1.32]), CV hospitalisation (1.12 [1.10–1.15]) and falls (1.06 [1.02–1.09]). DDIs with DOACs were associated with gastrointestinal bleeding (2.80 [1.35–5.81]). DDIs with CNS drugs were associated with stroke (1.19 [1.09–1.29]) and falls (1.32 [1.27–1.39]).</p> Conclusion <p>Potentially clinically significant DDIs were prevalent in older adults with AF and multimorbidity, with adverse clinical implications. Identifying these high-risk groups is essential for preventive strategies and effective clinical management.</p>

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Potentially Clinically Significant Drug-Drug Interactions in Older Adults with Atrial Fibrillation and Multimorbidity: Prevalence, Correlates, and Association with Adverse Clinical Outcomes in a Swedish National Register-Based Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月12日

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  • Cheima Amrouch,
  • Davide Liborio Vetrano,
  • Dirk De Bacquer,
  • Nicola Ferri,
  • Ine Simal,
  • Cecilia Damiano,
  • Lu Dai,
  • Amaia Calderón-Larrañaga,
  • Astrid D. H. Brys,
  • Anton De Spiegeleer,
  • Gregory Y. H. Lip,
  • Søren P. Johnsen,
  • Jonas W. Wastesson,
  • Kristina Johnell,
  • Delphine De Smedt,
  • Mirko Petrovic

摘要

Purpose

Current research on potentially clinically significant drug-drug interactions (DDIs) in individuals with atrial fibrillation (AF) has predominantly focused on DDIs involving direct oral anticoagulants (DOACs), with limited evidence regarding other medications. Our study aimed to: (i) assess the overall prevalence of DDIs; (ii) investigate potential demographic correlates of DDIs; and (iii) examine the association of DDIs with adverse clinical outcomes in a nationwide cohort of older adults with AF and multimorbidity.

Methodology

Data from the Swedish national registers were linked to establish a cohort with a 2-year follow-up of adults ≥ 65 years who, on 1 January 2017, had a diagnosis of AF, ≥ 1 comorbidity and were prescribed ≥ 2 medications (n = 192,716). This study describes the prevalence of 72 potentially clinically significant DDIs from an adapted explicit international consensus list and a review focused specifically on DDIs involving DOACs. Correlates of DDIs were assessed through logistic regressions. Cox regression analyses were conducted to examine the association between DDIs and adverse clinical outcomes: overall and cardiovascular (CV) mortality, overall and CV hospitalisation, stroke, bleeding, and falls.

Results

In the overall population, 37.5% presented with ≥ 1 potential DDI, with CV (33.8%) and central nervous system (CNS) drugs (12.4%) most frequently involved. Sex, age, and civil status were most consistently associated with DDIs. Individuals with ≥ 1 DDI had a higher hazard of CV death (hazard ratio 1.28 95% confidence interval (CI) [1.24–1.32]), CV hospitalisation (1.12 [1.10–1.15]) and falls (1.06 [1.02–1.09]). DDIs with DOACs were associated with gastrointestinal bleeding (2.80 [1.35–5.81]). DDIs with CNS drugs were associated with stroke (1.19 [1.09–1.29]) and falls (1.32 [1.27–1.39]).

Conclusion

Potentially clinically significant DDIs were prevalent in older adults with AF and multimorbidity, with adverse clinical implications. Identifying these high-risk groups is essential for preventive strategies and effective clinical management.