In older patients with atrial fibrillation assigned oral anticoagulants, obesity appears to be associated with reduced rates of stroke and mortality, according to findings from a post-hoc analysis of the AMADEUS trial.
Keitaro Senoo, MD, and Gregory Y.H. Lip, MD, both of the University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom, evaluated 1,588 patients aged at least 75 years enrolled in the randomized, open-label, noninferiority AMADEUS trial comparing the investigational agent idraparinux (Sanofi-Aventis) with vitamin K antagonists to prevent thromboembolism in patients with AF.
For the current analysis, patients were placed into BMI classifications: normal weight (18.5-25 kg/m2; n = 515); overweight (25-30 kg/m2; n = 711); and obese (≥ 30 kg/m2; n = 362). The study’s primary outcome was defined as the composite of CV death and stroke/systemic embolism.
The investigators used the chi-square test to compare the BMI groups when using categorical variables, and the Kruskal-Wallis test when comparing continuous variables. The researchers calculated outcomes in each BMI group based on overall rate of adverse events per 100 patient-years.
After adjusting for pertinent covariables, a multivariate Cox proportional hazard model revealed an association between obesity and lower risk for the primary composite outcome in the entire patient cohort (HR = 0.29; 95% CI, 0.11-0.77). Prior CAD also was linked to lower risk for the primary composite outcome (HR = 2.49; 95% CI, 1.37-4.5).
The overall rate of the composite of CV death and stroke/systemic embolism per 100 patient-years decreased significantly with increasing BMI category (normal weight = 5%, overweight = 3.2%, and obese = 1.5%; P for trend = .01).
Among patients in the warfarin-only group, the investigators observed an association with a trend for a lower risk for the primary composite outcome (HR = 0.53; 95% CI, 0.18-1.55).
In the entire cohort, Kaplan-Meier curves revealed a lower risk for CV death, stroke and stroke/systemic embolism among patients with obesity vs. the reference of normal BMI (log rank test, P = .03). Although a similar trend was seen in patients on warfarin, there was not sufficient power for significance.
Additionally, in the warfarin arm (n = 814), the researchers observed a trend toward improved time to therapeutic range (normal weight = 52%, overweight = 57%, and obese = 60%; P for trend < .001).
The researchers cited possible explanations for the association between obesity and improved stroke and mortality outcomes, including the use of more CVD prevention strategies, greater metabolic reserve and lower natriuretic peptide levels.
“Given the close relationship between [time in therapeutic range] and outcomes, obesity in elderly patients with AF might be linked with less adverse outcomes when compared with normal-weight patients,” the researchers wrote. “As we are limited in power to fully explore the association between [time in therapeutic range] and individual adverse outcomes in warfarin arm because of the low event rates, further studies are needed to explore this hypothesis.” – by Jen Byrne
Disclosure: Lip reports consulting and/or serving as a speaker for Astellas, Bayer/Jensen J&J, Bristol-Myers Squibb/Pfizer, Biotronik, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Merck, Microlife, Portola, Roche and Sanofi.