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Prior use of oral anticoagulants confers higher in-hospital mortality in intracerebral hemorrhage

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Gregg C. Fonarow

Prior use of non-vitamin K antagonist oral anticoagulants or warfarin was linked to higher in-hospital mortality vs. nonuse in patients with intracerebral hemorrhage, according to a presentation from the International Stroke Conference.

However, among those who had taken an oral anticoagulant, those taking a non-vitamin K antagonist oral anticoagulant had lower risk for in-hospital mortality than those taking warfarin, researchers reported.

The study by Taku Inohara, MD, PhD, from the Duke Clinical Research Institute, Duke University Medical Center, and colleagues, simultaneously published in JAMA, sought to better assess the association between preceding oral anticoagulant use and in-hospital mortality among patients with intracerebral hemorrhage.

“Non-vitamin K antagonist oral anticoagulants are increasingly used in clinical practice as alternatives to warfarin to prevent thromboembolic complications in high-risk patients with AF. Prior studies examining the outcomes of intracerebral hemorrhage among those on [ non-vitamin K antagonist oral anticoagulant] therapy have been relatively limited in size,” Gregg C. Fonarow, MD, Eliot Corday Professor of Cardiovascular Medicine and Science, director of the Ahmanson-UCLA Cardiomyopathy Center, co-chief of clinical cardiology, UCLA division of cardiology and co-director of the UCLA Preventative Cardiology Program at David Geffen School of Medicine at UCLA, told Cardiology Today. “There was an important need to better characterize how those who develop an intracerebral hemorrhage do after [non-vitamin K antagonist oral anticoagulant] therapy relative to those experiencing intracerebral hemorrhage either on warfarin or among those without prior oral anticoagulation.”

The researchers conducted a retrospective cohort study consisting of 141,311 patients with intracerebral hemorrhage (mean age, 68 years; 48% women) who were admitted to participating Get With the Guidelines-Stroke hospitals between October 2013 and December 2016.

In the cohort, 10.6% took warfarin and 3.5% took a non-vitamin K antagonist oral anticoagulant before intracerebral hemorrhage.

Concomitant single and dual antiplatelet agents were prescribed to 28% and 4.1% of patients before intracerebral hemorrhage, respectively.

Researchers found that patients with prior warfarin or non-vitamin K antagonist oral anticoagulant use tended to be older and had higher prevalence of atrial fibrillation and prior stroke.

According to the study, there was no significant difference between the three groups for acute intracerebral hemorrhage stroke severity as measured by NIH Stroke Scale.

The unadjusted in-hospital mortality rates were 32.6% for those taking warfarin, 26.5% for those taking non-vitamin K antagonist oral anticoagulants and 22.5% for those taking no oral anticoagulants.

The risk for in-hospital mortality was higher among patients with prior warfarin use (adjusted risk difference [aRD] = 9%; 97.5% CI, 7.9-10.1; adjusted OR = 1.62; 97.5% CI, 1.53-1.71) and higher among those with prior use of non-vitamin K antagonist oral anticoagulants (aRD= 3.3%; 97.5% CI, 1.7-4.8; adjusted OR = 1.21; 97.5% CI, 1.11-1.32) vs. patients with no prior oral anticoagulant use.

The risk for in-hospital mortality was lower among patients with prior use of non-vitamin K antagonist oral anticoagulants vs. patients with prior use of warfarin (aRD = 5.7%; 97.5% CI, 7.3 to 4.2; adjusted OR = 0.75; 97.5% CI, 0.69-0.81).

The difference in mortality between non-vitamin K antagonist oral anticoagulant-treated patients and warfarin-treated patients was numerically greater among those with prior use of dual antiplatelet agents (32.7% vs. 47.1%) compared with patients without prior antiplatelet therapy (P for interaction = .07).

Fonarow told Cardiology Today that further evaluation of the use of general and specific reversible agents and their associations with intracerebral hemorrhage outcomes is necessary, but the findings may help clinicians choose an anticoagulation strategy.

“Physicians should consider non-vitamin K oral anticoagulants as potentially a better anticoagulant strategy than warfarin in terms of the severity of their most devastating complication, intracerebral hemorrhage,” Fonarow said. “These findings may help to better inform selection of oral anticoagulation therapy.” – by Dave Quaile

Reference s :

Inohara T, et al. Abstract 131. Presented at: International Stroke Conference; Jan. 23-26, 2018; Los Angeles.

Inohara T, et al. JAMA. 2018;doi:10.1001/jama.2017.21917.

Disclosure s : Fonarow reports he receives research grants from PCORI and serves on the consultant and advisory board for AHA GWTG Steering Committee, Janssen, Medtronic and St. Jude Medical. Inohara reports he received grants from JSPS, Miyata Cardiac Research Foundation and Pfizer Health Research Foundation. Please see the study for all other authors’ relevant financial disclosures.