The Phase III PRESTIGE-AF trial has revealed both promising benefits and significant risks in using direct oral anticoagulants (DOACs) for stroke prevention among intracerebral hemorrhage (ICH) survivors with atrial fibrillation (AF). This groundbreaking study marks the first completed phase 3 trial comparing DOACs against no anticoagulation in this specific patient population.
Key Findings and Clinical Impact
The trial demonstrated a dramatic reduction in ischemic stroke occurrence among patients receiving DOACs. At a median follow-up of 1.4 years, the ischemic stroke event rate was 0.83 per 100 patient-years in the DOAC group, compared to 8.60 in the no-anticoagulation group (hazard ratio [HR] 0.05 [95% CI 0.01–0.36]; p<0.0001).
However, this benefit came with substantial risks. The DOAC group experienced a significantly higher rate of recurrent intracerebral hemorrhage, with 5.00 events per 100 patient-years versus 0.82 in the control group. The treatment did not meet the predetermined non-inferiority margin for bleeding risk (HR 10.89 [90% CI 1.95–60.72]).
Trial Design and Patient Population
The study was conducted across 75 hospitals in six European countries, including the UK, Germany, Austria, Spain, Italy, and France. Researchers enrolled 319 patients, randomly assigning them in a 1:1 ratio to either DOAC treatment (158 patients) or no anticoagulation (161 patients).
Eligible participants were adults aged 18 or older who had experienced spontaneous ICH and had AF requiring anticoagulation. All patients had a modified Rankin Scale score of four or less and were enrolled between 14 days to one year following their initial ICH.
Safety Profile and Mortality Outcomes
The safety analysis revealed serious adverse events in 44% of DOAC-treated patients compared to 55% in the control group. Mortality data showed 16 deaths in the DOAC cohort versus 21 in the no-anticoagulation group, suggesting no significant difference in overall survival.
Historical Context and Treatment Evolution
Previous research using vitamin K antagonists had shown promising results, with one large register-based study demonstrating a 45% decrease in mortality risk without significantly increasing recurrent ICH risk. DOACs were selected for this trial due to their approximately 50% lower risk of intracranial hemorrhages compared to vitamin K antagonists.
Clinical Implications and Future Directions
The findings underscore the complexity of managing stroke prevention in ICH survivors with AF. While DOACs effectively prevent ischemic strokes, the increased bleeding risk necessitates careful patient selection and risk stratification. The research team emphasizes the need for additional evidence from ongoing trials and the COCROACH meta-analysis, as well as exploration of safer therapeutic alternatives for specific patient groups.
