Major Bleeding Rates in Atrial Fibrillation Patients on Single, Dual, or Triple Antithrombotic Therapy

Abstract

Background: Patients with atrial fibrillation generally require anticoagulant therapy and, at times, therapy with additional platelet aggregation inhibitors. Data are scarce on bleeding rates in high-risk groups receiving combination therapy, such as the elderly or patients with a high CHA 2 DS 2 -VASc score. Methods: We conducted a nationwide cohort study of Danish patients with atrial fibrillation ≥50 years of age. Treatments were ascertained from a prescription database. These included no anticoagulant treatment, and treatment with vitamin K antagonists, direct oral anticoagulants, platelet inhibitors, and combinations of antithrombotic drugs. Incidence rates (IRs) of major bleeding and hazard ratios were estimated overall, and also stratified by treatment modality, age, CHA 2 DS 2 -VASc score, and comorbidity. Major bleeding was defined as bleeding requiring hospitalization or causing death. Results: We identified 272 315 patients with atrial fibrillation. Median age was 75 years (interquartile range, 67–83) and 47% were women. Over a total follow-up period of 1 373 131 patient-years (PYs), 31 459 major bleeds occurred (IR 2.3/100 PYs; 95% CI, 2.3–2.3/100 PYs). In comparison with vitamin K antagonist monotherapy, adjusted hazard ratios of major bleeding were 1.13 (95% CI, 1.06–1.19) for dual antiplatelet therapy, 1.82 (95% CI, 1.76–1.89) for therapy with a vitamin K antagonist and an antiplatelet drug, 1.28 (95% CI, 1.13–1.44) for therapy of a direct oral anticoagulant with an antiplatelet drug, 3.73 (95% CI, 3.23–4.31) for vitamin K antagonist triple therapy, and 2.28 (95% CI, 1.67–3.12) for direct oral anticoagulant triple therapy. Subgroup analyses showed similar patterns. The IR for major bleeding was 10.2/100 PYs among patients receiving triple therapy. Very high major bleeding rates occurred among patients on triple therapy aged >90 years (IR 22.8/100 PYs) or with a CHA 2 DS 2 -VASc score >6 (IR 17.6/100 PYs) or with a history of major bleeding (IR 17.5/100 PYs). Conclusions: Patients with atrial fibrillation on triple therapy experienced high rates of major bleeding in comparison with patients on dual therapy or monotherapy. The high bleeding rates observed in patients on triple therapy >90 years of age or with a CHA 2 DS 2 -VASc score >6 or with a history of a major bleeding warrants careful consideration of such therapy in these patients.

GARFIELD-AF model for prediction of stroke and major bleeding in atrial fibrillation: a Danish nationwide validation study

“…The primary safety endpoint involved a composite of haemorrhagic stroke or major bleeding. Major bleeding was defined as an organ-specific bleeding requiring hospitalisation 18. A list of ICD-10 codes used to compute these definitions can be found in Table S2.…”

Antithrombotic Therapy in Patients with Atrial Fibrillation and Acute Coronary Syndrome

“…To treat patients with both ACS and/or PCI and AF, studies have assessed the benefit of combination antithrombotic strategies comprising of both antiplatelet agents and OAC. The combination of OAC and DAPT (“triple therapy”) carries a significant increased risk of bleeding, compared to either DAPT or OAC alone, which is associated with excess mortality [ 10 , 11 ]. Therefore, several trials have evaluated the safety and efficacy of combination antithrombotic regimens dropping aspirin (“dual therapy”).…”

“…Compared to patients not taking OAC, all patients with OAC should be considered at increased risk of bleeding [ 10 ]. Thus, in every patient treated, bleeding risk should be minimized where possible.…”

“…Thus, there is a difference in antithrombotic treatment requirements between patients with AF and those with ACS, and where the two conditions coexist, careful consideration is needed to determine the optimal antithrombotic treatment to reduce the risks of future ischaemic events associated with both conditions [ 8 , 9 ]. However, a combination of DAPT and OAC (also referred to as “triple therapy”), confers a significant risk for major bleeding, which is up to four times higher than that associated with OAC alone [ 10 ]. Since major bleeding after PCI has been shown to be associated with increased mortality [ 11 ], the bleeding risk should be kept to a minimum.…”

Triple therapy in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention/stenting

“…8,9 Triple therapy (TT) using DAPT in combination with an OAC effectively prevents vascular ischemic events but is associated with considerably increased risk of bleeding. 10…”