Direct oral anticoagulants (DOACs) are an effective and safe alternative to warfarin treatment for patients with nonvalvular atrial fibrillation (AFib) and hyperthyroidism, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

The use of DOACs has been increasing in recent years for patients with nonvalvular AFib, but limited data are available on the effectiveness and safety of DOACs compared with warfarin in nonvalvular AFib and hyperthyroidism. The goal of the current study was to compare the outcomes of DOAC vs warfarin use among patients with nonvalvular AFib, either with or without concomitant hyperthyroidism.

The retrospective study included data from the Taiwan National Health Insurance program, a compulsory universal healthcare system in Taiwan with information on more than 23 million patients. The researchers identified 78,215 patients with AFib who received any DOAC between June 2012 and December 2017.

Hyperthyroidism-associated AFib was defined as having a diagnosis of hyperthyroidism between 24 months before and 3 months after diagnosis of nonvalvular AFib. Of 4394 patients with both conditions, 3213 were receiving DOACs and 1181 were treated with warfarin.


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Of 70,155 patients with nonvalvular AFib who did not have hyperthyroidism, 53,591 were treated with DOACs and 16,564 were receiving warfarin.

Propensity score-based stabilized weights were used to balance covariates across the study groups, and patients were matched 1:4 by baseline CHA2DS2-VASc score, a measure of stroke risk in AFib. This led to the matching of 3213 and 12,852 patients with nonvalvular AFib who received DOACs with and without hyperthyroidism, respectively, and 1181 and 4724 patients who received warfarin with and without hyperthyroidism, respectively.

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In the group with nonvalvular AFib and hyperthyroidism, risk for ischemic stroke/systemic embolism was similar with DOACs vs warfarin, whereas risk for major bleeding was significantly lower with DOAC treatment (hazard ratio [HR], 0.65; 95% CI, 0.44-0.96; P =.0295).

In the group with nonvalvular AFib without hyperthyroidism, risk for ischemic stroke/systemic embolism was lower among patients treated with DOACs compared with warfarin (HR, 0.89; 95% CI, 0.83-0.95; P =.0010), as was the risk for intracerebral hemorrhage (HR, 0.51; 95% CI, 0.45-0.58; P <.0001), hospitalized gastrointestinal bleeding (HR, 0.49; 95% CI, 0.43-0.56; P <.0001), and major bleeding (HR, 0.52; 95% CI, 0.48-0.57; P <.0001).

In terms of cumulative risk, patients with nonvalvular AFib and concomitant hyperthyroidism who received DOACs had comparable risks to those for patients without hyperthyroidism for all effectiveness and safety outcomes. In comparison, patients with AFib and concomitant hyperthyroidism who received warfarin had comparable safety outcomes, but risk for ischemic stroke/systemic embolism was significantly lower (HR, 0.61; 95% CI, 0.43-0.86; P =.0050) compared with those without hyperthyroidism.

The study had several limitations, including missing data on electrocardiography and imaging results, smoking history, lipid profile, renal and liver function, and time in therapeutic range with warfarin therapy. Furthermore, miscoding and misclassification may have caused confounding bias.

“Among [Asian patients with AFib and] concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study,” concluded the researchers.

Disclosure: One study author declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Reference

Chan YH, Wu LS, See LC, et al. Direct oral anticoagulants in atrial fibrillation patients with concomitant hyperthyroidism [published online February 3, 2020]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa050