DOACs lower stroke, raise hemorrhage risk in those with prior brain hemorrhage plus AF
Key takeaways:
- Direct oral anticoagulants may lower stroke risk in people with prior intracerebral hemorrhage and atrial fibrillation.
- Part of this benefit was negated by an observed increased risk for secondary hemorrhage.
The benefit of direct oral anticoagulants on stroke risk in patients with prior intracerebral hemorrhage and atrial fibrillation was partially offset by increased risk for future hemorrhage risk, a speaker reported.
The results of the PRESTIGE-AF trial evaluating the effects of direct oral anticoagulants (DOACs) in patients with AF and prior intracerebral hemorrhage (ICH) were presented at the International Stroke Conference.
“Stroke prevention in ICH survivors is an important unmet need. ICH patients are at increased risk of recurrent ICH,” Roland Veltkamp, MD, professor of neurology and chair of stroke medicine in the department of brain sciences at Imperial College London, said during the presentation. “Traditionally, the focus of stroke prevention in ICH survivors has been on the prevention of recurrent intracerebral hemorrhage. However, there is growing evidence that ICH survivors also have increased risks of ischemic events, and a particularly vulnerable patients population are ICH survivors with AF.”
PRESTIGE-AF was a phase 3b, multicenter, prospective, randomized trial that enrolled 319 patients at 63 sites across Europe.
Patients with AF and prior ICH were randomly assigned to a DOAC or no oral anticoagulation and were followed up at 1, 6, 12, 24 and 36 months.
The primary efficacy endpoint was incidence of ischemic stroke. The primary safety endpoint was recurrent ICH.
During a mean of 1.43 years, no participants were lost to follow-up. The average age was about 79 years, nearly all participants were white and approximately 35% were women.
Among those assigned to a DOAC, 53.8% used apixaban (Eliquis, Bristol Myers Squibb/Pfizer), 20.9% used dabigatran (Pradaxa, Boehringer Ingelheim), 18.4% used edoxaban (Savaysa, Daiichi Sankyo) and 5.7% used rivaroxaban (Xarelto, Janssen/Bayer). In the control group, 67% of patients had no anticoagulation or antiplatelet therapy, 30% used aspirin and 2% used clopidogrel.
Among patients with AF and prior ICH within 12 months, DOAC use was associated with lower adjusted risk for subsequent first ischemic stroke (adjusted HR = 0.05; 95% CI, 0.01-0.38; P < .001), according to the presentation.
Despite the reported stroke risk benefit, DOACs did not meet noninferiority compared with the control group for recurrent ICH (aHR = 11.2; 95% CI, 2.01-62.86; P for noninferiority = .961).
For several key secondary endpoints, DOAC use demonstrated trends toward reduced risk for all-cause mortality (aHR = 0.81; 95% CI, 0.42-1.55), CV death (aHR = 0.52; 95% CI, 0.21-1.28), major adverse cardiac events (aHR = 0.6; 95% CI, 0.25-1.36) and all stroke and systemic embolism (aHR = 0.55; 95% CI, 0.28-1.04). However, DOAC use was also associated with increased risk for any major hemorrhage (aHR = 4.47; 95% CI, 1.82-13.44) and any ICH (aHR = 7.53; 95% CI, 2.11-47.87). These data should be interpretated with caution due to the wide confidence intervals and the added factor that the hazard ratios were not adjusted for multiplicity, according to the presentation.
Veltkamp reported that for individuals with AF and prior ICH, the number needed to treat with a DOAC to prevent one stroke per year was 13, but the number needed to harm and cause one subsequent intracranial hemorrhage was 24.
“Because ICH survivors with AF have a high risk of ischemic stroke, they are in need of effective preventive treatments. DOACs effectively reduced the risk of ischemic stroke and of other ischemic events in PRESTIGE-AF; however, a part of this benefit was offset by major bleeding side effects of DOACs, in particular recurrent ICH.” Veltkamp said during the presentation. “Composite endpoints suggest a quantitative net benefit of DOACs, but a different impact of particular events still has to considered.”
Collapse
Veltkamp R, et al. LB37. Presented at: International Stroke Conference; Feb. 5-7, 2025; Los Angeles (hybrid meeting).