Does adding statins to DOACs reduce the risk of major bleeding in patients with non-valvular atrial fibrillation?

Previous conflicting results

Due to the frequent concurrent occurrence of dyslipidemia and atrial fibrillation (AF), DOACs are administered with statins in many patients. Previous studies have shown both a reduction in the risk of intracranial bleeding in patients treated concurrently with atorvastatin and DOACs, and a higher risk of major bleeding with the combination of simvastatin or lovastatin with dabigatran from the DOACs group. The authors of the recently published study attempted to clarify the risk of major bleeding in patients with non-valvular AF who are concurrently taking DOACs and various doses of statins compared to patients with DOACs without statin treatment.

Data from a large national database

This was a retrospective cohort study utilizing data from nearly 91,000 patients with non-valvular AF from the Taiwanese National Health Insurance Research Database (NHIRD), who were using one of the four DOACs: dabigatran, rivaroxaban, apixaban, or edoxaban from 2012 to 2017. The primary parameter monitored was the occurrence of major bleeding—defined as hospitalization or emergency treatment due to intracerebral bleeding, gastrointestinal bleeding, urogenital tract bleeding, or other locations.

The incidence of bleeding adjusted for potential confounding factors was compared between patients taking statins and those not taking statins. Patients on statins were further divided into groups with low to moderate doses of statins and high doses of statins (i.e., atorvastatin 40–80 mg/day or rosuvastatin 20 mg/day). Three-month intervals covered by DOAC + statin treatment or DOACs only were evaluated.

Findings

Among the 90,731 enrolled patients, 56% were men, and the average age of the entire population was 75 years. The average HAS-BLED score was 3.0, and the average CHA₂DS₂-VASc score was 4.59. 52% of patients had congestive heart failure, 46% had cerebrovascular disease, and 41% had diabetes mellitus.

Compared to using DOACs without statins, the concurrent use of DOACs and statins was associated with a significantly lower incidence of all major bleeding by 20% (incidence rate ratio [IRR] 0.8; 95% confidence interval [CI] 0.72–0.81). A lower incidence of major bleeding was observed with both low to moderate doses of statins (IRR 0.8; 95% CI 0.74–0.84) and high doses of statins (IRR 0.8; 95% CI 0.74–0.88).

The risk of intracranial bleeding was also 20% lower with the concurrent use of DOACs and statins (IRR 0.8; 95% CI 0.66–0.93), and the risk of gastrointestinal bleeding was 30% lower (IRR 0.7; 95% CI 0.69–0.79). The risk of urogenital tract bleeding and bleeding at other sites was not significantly affected by concurrent statin use.

Regarding intracranial bleeding, differences were found between men and women. The protective effect of statin administration was observed only in women (IRR 0.67; 95% CI 0.51–0.89) and not in men (IRR 0.87; 95% CI 0.70–1.08). However, the risk of intracranial bleeding was not increased in men by adding statins.

Conclusion

In patients with non-valvular atrial fibrillation taking direct oral anticoagulants, adding a statin at any dose reduces the risk of major bleeding. Given the cardioprotective effects of statins, it is therefore advisable to consider their administration in all patients with dyslipidemia treated with DOACs.

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Source: Wu H. H., Chang S. H., Lee T. H. et al. Concurrent use of statins decreases major bleeding and intracerebral hemorrhage in non-valvular atrial fibrillation patients taking direct oral anticoagulants—a nationwide cohort study.Front Cardiovasc Med 2022 Aug 8; 9: 969259, doi: 10.3389/fcvm.2022.969259.