Effectiveness and safety of anticoagulant therapy in patients with AF at low stroke risk
Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study
Introduction and methods
Background and aim of the study
Treatment with an oral anticoagulant is recommend in patients with AF and a CHA2Ds2-VASc score of ≥2 for males or ≥3 for females. In patients with a low risk of stroke (one non-sex-related CHA2DS2-VASc point), current guidelines recommend to individualize treatment with OAC based on net clinical benefit and patient preferences [1,2]. This observational study assessed the safety and effectiveness of DOAC, VKA or no treatment with an anticoagulant in patients with AF and a low stroke risk.
Patients were selected and pooled from four European databases from Denmark, Norway, Scotland, and the Stockholm region in Sweden. A total of 59076 patients with newly diagnosed AF and low stroke risk were included in the study. Low stroke risk was defined as a CHA2DS2-VASc score of 1 in male patients and a CHA2Ds2-VASc score of 2 in female patients. There were three possible levels of anticoagulant treatment status in the study: no treatment, DOAC treatment, and VKA treatment. Patients were followed until the first occurrence of either an outcome of interest, death, emigration, antiplatelet prescription, increase in CHA2DS2-VASc score or end of the 2.5 year follow-up.
The effectiveness outcome was a composite of ischemic or unspecified stroke. The primary safety outcome was any major bleed. Secondary safety outcomes included gastrointestinal (GI) bleeds or intracranial hemorrhage (ICH) as separate outcomes.
There was a composite outcome of stroke, major bleed, or death. In addition, a net clinical benefit was calculated (ischemic rate off treatment − ischemic rate on treatment) − weight × (ICH rate on treatment − ICH rate off treatment), with weight 1.0, 1.5 or 2.0.
DOAC vs. no treatment
- Compared to no treatment, treatment with DOAC was associated with a lower rate of stroke (HR 0.72, 95% CI 0.55–0.94, NNT-y: 511), but higher rate of bleeds (HR 1.26, 95% CI 1.00–1.58,
- The higher bleeding rate was primarily driven by a higher rate of GI bleeds (HR 1.48, 95% CI 1.05–2.08; NNT-y: 675). There was no significant difference in ICH (HR 0.84, 95% CI 0.54–1.30, NNT-y: 3473). These outcomes yielded a positive net clinical benefit for DOAC treatment, at each weight given to an ICH.
VKA vs. no treatment
- There was no significant difference between VKA and no treatment for either stroke rate (HR 0.81, 95% CI 0.59–1.09, NNT-y: 754) or bleeding rate (HR 1.44, 95% CI 0.83–2.50, NNT-y: 324). There was also no significant difference for ICH rate between VKA treatment and no treatment (HR 1.37, 95% CI 0.88–2.14, NNT-y: 1501). This yielded a neutral net clinical benefit, at each weight given to an ICH.
DOAC vs. VKA
- Stroke and bleeding rates were not significantly different between DOAC and VKA treatment (HR 0.92, 95% CI 0.70–1.22, NNT-y: 2506; and HR 0.85, 95% CI 0.69–1.06, NNT-y: 807, respectively).
- Compared with VKA, treatment with DOAC was associated with a significantly lower ICH rate (HR 0.63, 95% CI 0.42-0.94, NNT-y: 1096). This yielded a positive net clinical benefit for DOAC vs VKA, which was significant in two of the three weights given to an ICH.
The results of this observational study suggest that treatment with DOAC may be associated with a positive net clinical benefit compared with VKA and no anticoagulation treatment in patients with AF and a low stroke risk. A randomized controlled trial is needed to confirm this association.