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Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation.

Publication ,  Journal Article
Patel, SM; Braunwald, E; Steffel, J; Boriani, G; Palazzolo, MG; Antman, EM; Bohula, EA; Carnicelli, AP; Connolly, SJ; Eikelboom, JW; Gencer, B ...
Published in: Circulation
March 19, 2024

BACKGROUND: The efficacy and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. METHODS: We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. RESULTS: Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HRadj], 0.80 [95% CI, 0.73-0.88]; P<0.001), with a generally consistent effect across BMI (Ptrend across HRs, 0.48). NOACs also reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82-0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [Ptrend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HRadj, 0.91 [95% CI, 0.87-0.95]; P<0.001; death, HRadj, 0.91 [95% CI, 0.86-0.97]; P=0.003), these benefits were attenuated at higher BMI (Ptrend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW. CONCLUSIONS: The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.

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Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

March 19, 2024

Volume

149

Issue

12

Start / End Page

932 / 943

Location

United States

Related Subject Headings

  • Warfarin
  • Treatment Outcome
  • Stroke
  • Randomized Controlled Trials as Topic
  • Humans
  • Hemorrhage
  • Cardiovascular System & Hematology
  • Body Weight
  • Body Mass Index
  • Atrial Fibrillation
 

Citation

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Patel, S. M., Braunwald, E., Steffel, J., Boriani, G., Palazzolo, M. G., Antman, E. M., … COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) Investigators, . (2024). Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation. Circulation, 149(12), 932–943. https://doi.org/10.1161/CIRCULATIONAHA.123.066279
Patel, Siddharth M., Eugene Braunwald, Jan Steffel, Giuseppe Boriani, Michael G. Palazzolo, Elliott M. Antman, Erin A. Bohula, et al. “Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation.Circulation 149, no. 12 (March 19, 2024): 932–43. https://doi.org/10.1161/CIRCULATIONAHA.123.066279.
Patel SM, Braunwald E, Steffel J, Boriani G, Palazzolo MG, Antman EM, Bohula EA, Carnicelli AP, Connolly SJ, Eikelboom JW, Gencer B, Granger CB, Morrow DA, Patel MR, Wallentin L, Ruff CT, Giugliano RP, COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) Investigators. Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation. Circulation. 2024 Mar 19;149(12):932–943.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

March 19, 2024

Volume

149

Issue

12

Start / End Page

932 / 943

Location

United States

Related Subject Headings

  • Warfarin
  • Treatment Outcome
  • Stroke
  • Randomized Controlled Trials as Topic
  • Humans
  • Hemorrhage
  • Cardiovascular System & Hematology
  • Body Weight
  • Body Mass Index
  • Atrial Fibrillation