In trials comparing newer oral anticoagulants with warfarin for prevention of stroke in patients with atrial fibrillation, many deaths were from cardiac causes but not from stroke or bleeding, according to a new analysis.
    “Interventions beyond anticoagulation are needed to further reduce mortality in AF,” Antonio Gómez-Outes, MD, PhD, from the division of pharmacology and clinical drug evaluation, Spanish Agency for Medicines and Medical Devices, Madrid, and colleagues wrote.
    The researchers examined the causes of death in patients from anticoagulation trials, who often have high mortality rates.
    They analyzed 71,683 patients from four trials, covering 134,046 patient-years of follow-up, during which 9% of patients died.
    The adjusted mortality rate was 4.72% per year (95% CI, 4.19-5.28), according to the researchers.
    Among all deaths, 46% were from cardiac causes vs. 5.7% from nonhemorrhagic stroke or systemic embolism and 5.6% from a hemorrhagic cause, they found.
    Compared with those who survived, those who died had a higher rate of HF (OR = 1.75; 95% CI, 1.25-2.44), permanent or persistent AF (OR = 1.38; 95% CI, 1.25-1.52) and diabetes (OR = 1.37; 95% CI, 1.11-1.68), according to the researchers.
    Those who died were more likely to be men (OR = 1.24; 95% CI, 1.13-1.37), to be older (mean difference, 3.2 years; 95% CI, 1.6-4.8) and to have lower creatinine clearance (–9.9 mL/min; 95% CI, –11.3 to –8.4), Gómez-Outes and colleagues wrote.
    The researchers observed a small but significant reduction in all-cause death for those assigned a newer oral anticoagulant vs. those assigned warfarin (difference, –0.42% per year; 95% CI, –0.66 to –0.18), driven by fewer fatal bleeds.
    In a related editorial, Stuart J. Connolly, MD, from the department of medicine, Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada, wrote the analysis “points to the important mortality benefit of the [newer agents] over warfarin, and partially explains this through quite large relative reductions in immediately fatal bleeding.”

    Stuart J. Connolly
    However, he wrote, “The longer-term adverse consequences of major bleeding episodes have been quite clearly seen in other analyses of the [trials of newer agents] and in other studies. The mechanisms by which these effects occur remain largely obscure and are an area of potentially rewarding research for the future.” – by Erik Swain
    Disclosure: The researchers report no relevant financial disclosures. Connolly reports receiving consulting, lecture fees and institutional research grants from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Pfizer and Portola.