Disclosures: Giugliano reports he received consultant fees from Bristol Myers Squibb, Daiichi Sankyo, Janssen, Merck, Pfizer, Portola, SAJA Pharmaceuticals and Servier; and grant support from Anthos Therapeutics, AstraZeneca, Daiichi Sankyo, Johnson & Johnson, Merck, Pfizer and Sanofi. Please see the study for all other authors’ relevant financial disclosures.
March 03, 2021
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Lower dose of edoxaban confers reduced risk for certain events vs. higher dose

Disclosures: Giugliano reports he received consultant fees from Bristol Myers Squibb, Daiichi Sankyo, Janssen, Merck, Pfizer, Portola, SAJA Pharmaceuticals and Servier; and grant support from Anthos Therapeutics, AstraZeneca, Daiichi Sankyo, Johnson & Johnson, Merck, Pfizer and Sanofi. Please see the study for all other authors’ relevant financial disclosures.
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Compared with those on a higher dose, patients on a lower-dose edoxaban regimen had lower risk for a composite of stroke, major bleeding and death, according to results published in the Journal of the American College of Cardiology.

“In the double-blind, three-arm randomized ENGAGE AF-TIMI 48 trial, both the higher-dose and lower-dose edoxaban regimens, which represent a 50% reduction in dose, were noninferior to well-managed warfarin for the prevention of stroke/systemic embolic event in patients with atrial fibrillation. Although both regimens signicantly reduced the risk of major bleeding and cardiovascular death, lower-dose edoxaban increased the incidence of ischemic stroke by 41% compared with warfarin,” Jan Steffel, MD, FESC, FHRS, senior attending cardiologist at University Heart Center Zurich, and colleagues wrote. “These data led to the approval of higher-dose edoxaban (but not lower-dose edoxaban) for stroke prevention in patients with AF worldwide.”

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In an analysis of the ENGAGE AF TIMI-48 trial, researchers compared patients randomly assigned lower-dose edoxaban (Savaysa, Daiichi Sankyo; 30 mg daily in most patients; n = 7,002; mean age, 72 years; 39% women) with patients assigned higher-dose edoxaban (60 mg daily in most patients; n = 7,012; mean age, 72 years; 38% women) for the primary net clinical outcome of stroke/systemic embolism, major bleeding or death.

During a median follow-up of 2.8 years, the lower-dose edoxaban group had reduced risk for reaching a primary outcome compared with the higher-dose edoxaban group (7.26% vs. 8.01%; HR = 0.9; 95% CI, 0.84-0.98; P = .014), the researchers wrote.

The secondary composite outcome of disabling stroke/life-threatening bleeding/all-cause mortality did not differ between the groups, nor did the tertiary composite outcome of stroke/systemic embolism/life-threatening bleeding or all-cause mortality, according to the researchers.

Further comparison showed the lower-dose edoxaban group had higher risk for stroke/systemic embolism (2.04% vs. 1.56%; HR= 1.31; 95% CI, 1.12-1.52; P < .001) and lower risk for major bleeding, intracranial hemorrhage, major gastrointestinal bleeding and life-threatening bleeding compared with the higher-dose edoxaban group.

Robert P. Giugliano

“For the vast majority of patients, the currently approved ‘full-dose’ regimen of edoxaban (60 mg/30 mg) should be used in patients with atrial fibrillation. If the dose is reduced by 50%, then there is significantly less prevention of ischemic stroke, much less bleeding, similar mortality, and overall, the net outcomes are comparable,” Robert P. Giugliano, MD, ScM, cardiovascular medicine specialist at Brigham and Women’s Hospital, associate professor of medicine at Harvard Medical School and senior investigator of Brigham and Women’s TIMI Study Group, told Healio. “Therefore, there may be some patients at very high risk of bleeding where a physician-patient discussion would be helpful to discuss the advantages/disadvantages of the two dosing regimens.”

For more information:

Robert P. Giugliano, MD, ScM, can be reached at rgiugliano@bwh.harvard.edu