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The factor Xa inhibitor edoxaban (Savaysa) was found to be safer than warfarin when taken for stroke prevention among atrial fibrillation (Afib) patients with bioprosthetic valves, a subanalysis of the the ENGAGE AF-TIMI 48 trial found.

While the yearly rate of stroke or systemic embolic events was no different whether this high-risk cohort got edoxaban or warfarin, lower-dose edoxaban (30 mg) was associated with a reduced rate of major bleeding (0.76% versus 6.27% with warfarin, HR 0.12, 95% CI 0.01-0.95), according to the . Major bleeding rates with higher-dose edoxaban were about the same as for warfarin.

However, compared with warfarin, higher-dose edoxaban (60 mg) was associated with fewer combined strokes, systemic embolic events, major bleeds, and deaths annually (7.53% versus 15.77%, HR 0.46, 95% CI 0.23-0.91). Yearly MI, stroke, and cardiovascular mortality were lower as well with higher-dose edoxaban (4.32% versus 11.07%, HR 0.36, 95% CI 0.15-0.87).

Similarly, the lower-dose edoxaban recipients had lower annual rates of stroke, systemic embolic events, major bleeding, and death combined (7.03% versus 15.77%, HR 0.43, 95% CI 0.21-0.88), reported , of Brigham and Women's Hospital in Boston and the TIMI Study Group.

Other endpoints were indistinguishable between treatments.

"Our analysis suggests that edoxaban appears to be a reasonable alternative to warfarin in patients with Afib and remote bioprosthetic valve implantation," Giugliano's team concluded.

“This is big,” said Mark Link, MD, of UT Southwestern Medical Center in Dallas, in a telephone interview with 名媛直播. “Bioprosthetic valves are no longer contraindicated for NOACs.”

“Lots of patients have bioprosthetic valves, so this opens the door for a lot of people,” said Link, who was not involved in Giugliano’s study.

The FDA already approved edoxaban in 2015 for stroke prevention for nonvalvular Afib patients with renal impairment. The drug was also indicated for treating deep vein thrombosis and pulmonary embolism.

There were 21,105 patients enrolled in the main Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial, which randomized patients to once-daily edoxaban 60 mg, edoxaban 30 mg, or warfarin.

For the present study, Giugliano's group analyzed the 191 Afib patients with bioprosthetic valves (n=131 mitral, n=60 aortic) -- from surgical or transcatheter implantation -- excluding those with mechanical valves and moderate-to-severe mitral stenosis.

Baseline characteristics were well-balanced between groups. Patients were followed for a median 2.8 years, during which those with decreased clearance had their edoxaban dosage halved.

“This history behind this is that individuals that have valvular Afib have generally been excluded from the NOAC trials because of the fear that they have a higher rate of thromboembolism and left atrial clots,” Link said. “But on closer inspection, it’s really mitral stenosis that you want to exclude. Because of the clamor of not giving NOACs to people with valvular disease, that extended to people with bioprosthetic valves too.”

“Non-valvular Afib really means non-mitral stenosis and non-mechanial valve Afib,” he emphasized, citing a study in which dabigatran fared poorly in mechanical valves that “scared everyone off NOACs and mechanical valves.”

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