Concurrent use of statins decreases major bleeding and intracerebral hemorrhage in non-valvular atrial fibrillation patients taking direct oral anticoagulants—A nationwide cohort study

Abstract

BackgroundStatins are frequently prescribed with direct oral anticoagulants (DOACs), and previous studies have raised concerns about the increased risk of intracerebral hemorrhage or other major bleeding in concurrent statins and DOACs use. The objective of this study is to evaluate the risk of major bleeding in non-valvular atrial fibrillation patients taking DOACs with or without statins.MethodsThis nationwide, retrospective cohort study used data from the Taiwan National Health Insurance Research Database, enrolled a total of 90,731 non-valvular atrial fibrillation patients receiving rivaroxaban, dabigatran, apixaban or edoxaban from January 1st, 2012 to December 31st, 2017. Major bleeding was defined as a hospitalization or emergency department visit with a primary diagnosis of intracerebral hemorrhage, gastrointestinal tract bleeding, urogenital tract bleeding, or other sites of bleeding. Adjusted incidence rate ratios (IRR) and differences of major bleeding between person-quarters of DOACs with or without statins were estimated using a Poisson regression and inverse probability of treatment weighting using the propensity score.Results50,854 (56.0%) of them were male with a mean age of 74.9 (SD, 10.4) years. Using DOACs without statins as a reference, the adjusted IRR for all major bleedings in concurrent use of DOACs and statins was 0.8 (95% CI 0.72–0.81). Lower major bleeding risk was seen in both low-to-moderate-intensity statins (IRR: 0.8, 95% CI 0.74–0.84) and high-intensity statins (IRR: 0.8, 95% CI 0.74–0.88). Concurrent use of DOACs and statins decreased the risk for intracerebral hemorrhage with an IRR of 0.8 (95% CI 0.66–0.93), and gastrointestinal tract bleeding with an IRR of 0.7 (95% CI 0.69–0.79). The protective effect of statins on intracerebral hemorrhage was observed only in female patients (IRR 0.67, 95% CI 0.51–0.89), but not in male patients (IRR 0.87, 95% CI 0.70–1.08).ConclusionsAmong non-valvular atrial fibrillation patients who were taking DOACs, concurrent use of statins decreased major bleeding risk, including intracerebral hemorrhage and gastrointestinal tract bleeding. Considering this and other cardioprotective effects, statins should be considered in all eligible patients prescribed with DOACs.

Statin use in total joint arthroplasty: a systematic review

“…Due to the possibility of drug-drug interactions that could impact bleeding risks, particularly in the setting of surgery, research has been conducted on the interaction between Statins and anticoagulants, including warfarin. While some evidence suggests that Statins may raise the risk of bleeding when combined with warfarin, other studies suggest that Statins may lower the risk of bleeding in people using DOACs 33 , 34 . The effects may differ based on the particular statin and anticoagulant used, as well as patient-specific factors, and the evidence is not totally consistent.…”

Current status of proton pump inhibitor usage in patients with acute coronary syndrome and nonvalvular atrial fibrillation: A cross-sectional study

“…The reason may be because of the relatively low actual anticoagulation rate despite the high proportion of patients at high risk in our study. Some studies have indicated that amiodarone, statins, and antibiotics could potentially elevate the risk of bleeding when taken with OACs [31][32][33][34][35][36][37] . However, the limited usage of OAC in the study may cause doctors to overlook the potential bleeding risk caused by drug interactions.…”

Association of statin use and lipid levels with cerebral microbleeds and intracranial hemorrhage in patients with atrial fibrillation: A prospective cohort study

“…2 An increased risk of ICH associated with statins and low cholesterol levels is supported by other studies, 3,4 but these associations remain controversial. [5][6][7] Cerebral microbleeds (CMBs) are hypointense lesions on T2-weighted gradient-echo magnetic resonance imaging (MRI). They are considered to be an asymptomatic precursor of ICH, especially in patients with a high burden of CMBs, 8,9 while they are also associated with an increased risk for ischemic stroke.…”

“…2 An increased risk of ICH associated with statins and low cholesterol levels is supported by other studies, 3,4 but these associations remain controversial. 5–7…”