High risk of ischemic and hemorrhagic events in AF patients with OAC contraindication
Patients With Atrial Fibrillation Who Are Not on Anticoagulant Treatment Due to Increased Bleeding Risk Are Common and Have a High Risk of Stroke
OAC therapy effectively reduces the risk of ischemic stroke in AF patients, but comes with an increased risk of bleeding. Large trials of patients who did not have an increased baseline risk of bleeding have shown a favorable risk-to-benefit ratio with OACs [1-3]. However, important subsets of AF patients with a higher risk of bleeding were excluded from these trials.
In this study, in a real-world population the risk of ischemic stroke and major bleeding was assessed in AF patients who recently had a sufficiently severe bleeding event, such that OAC were considered contraindicated by their treating physician. Moreover, the aim was to identify subgroups in which these risks are increased.
For this purpose, patients (>18 years) with a diagnosis code for AF and a registered OAC contraindication were identified from the multi-payer Truven Health Market Scan Commercial and the Medicare Supplemental Research databases, from January 1, 2009, to December 31, 2013. Patients were required to have had ≥12 months of continuous enrollment after the index event, with the exception of patients who died in hospital. The primary study endpoint was the occurrence of ischemic stroke. Secondary endpoints were any stroke, hemorrhagic stroke, death from any cause, CV death, stroke-related death, and any major non-intracranial bleeding (requiring transfusion or surgical intervention). The stroke risk, as well as the bleeding risk, were compared with the adjusted risks for a general population of AF patients reported in literature [4-7].
- Among AF patients with OAC contraindications, >4 out of 5 had a CHA₂DS₂-VASc score of >1 and 42.9% had a CHA₂DS₂-VASc-score of ≥4.
- The incidence of ischemic and hemorrhagic stroke was 4.1% and 3.6%, respectively, in the overall study cohort and 12.2% and 20.3%, respectively, among patients with a previous cerebral or intracranial hemorrhage.
- Hemorrhagic stroke occurred in 1 out of 5 patients with previous intracranial or intracerebral hemorrhage.
- In the overall study population, the incidence of ischemic stroke increased with increasing CHADS₂ or CHA₂DS₂-VASc scores (P<0.001), and was consistent with current reference rates for a general population of AF patients.
- The risk of hemorrhagic stroke also increased with increasing CHADS₂ /CHA₂DS₂-VASc, but the relationship was less steep than for ischemic stroke.
- For patients with previous intracranial or intracerebral hemorrhage, the incidence of stroke seemed to be unrelated to CHADS₂ or CHA₂DS₂-VASc score.
- The risk of major bleeding in the entire study population was increased with increasing CHA₂DS₂-VASc and was considerably higher than in an OAC-treated general population of AF patients.
- The risk of dying within 1 year was 12.7% for the overall patient cohort and 23.0% for patients with a history of intracerebral or intracranial hemorrhage.
A considerable number of patients with AF are not treated with OAC because of a bleeding-related contraindication, although they are considered to have high stroke risk according to their CHADS₂ or CHA₂DS₂-VASc score. These data show that these OAC-naive patients have a considerably high risk of ischemic and hemorrhagic stroke events, as well as death, and these risks are particularly high in patients with previous intracranial hemorrhage. These results suggest that new ways to prevent stroke are needed in this population.