Appropriate DOAC dose reduction boosts safety, does not compromise efficacy

Direct oral anticoagulants (DOACs) are appropriately dosed in most Asian patients with non-valvular atrial fibrillation (NVAF), a new study has found. Proper dose reductions may also help reduce clinically significant bleeding without compromising on efficacy.

The researchers conducted a single-centre prospective analysis of 2,216 NVAF patients, categorized into five groups according to DOAC dosing: appropriate standard-dose (n=907), appropriate low-dose (n=833), overdose (n=117), under-dose (n=338), and contraindication (n=21). Major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction, and stroke/systemic embolism, was set as the primary efficacy endpoint.

After a mean follow-up of 407.2±388.3 days, the corresponding prevalence rate of MACE in each group was 3.2 percent, 7.4 percent, 3.3 percent, and 4.6 percent; no figures were given for contraindicated patients.

Unadjusted analysis found that patients receiving low-dose DOACs were at a significantly higher risk of MACE, though this was completely attenuated after complete control for confounders (hazard ratio [HR], 0.868, 95 percent confidence interval [CI], 0.440–1.710; p=0.682). This suggests that appropriate dose reductions may not interfere with NOAC efficacy.

Moreover, appropriate dose reduction led to a safer treatment, cutting the risk of clinically significant bleeding by nearly 40 percent (HR, 0.646, 95 percent CI, 0.469–0.890; p=0.007). No such impacts were reported for major and gastrointestinal bleeding.

“In the real-world Asian clinical practice, four-fifths of the NVAF patients treated with DOACs for stroke prevention received recommended doses according to the standard criteria for dose reduction,” the researchers said. “Compliance with the standard criteria is of paramount importance in the Asian real-world clinical practice.”