Oral Anticoagulation Reduces Risk for Adverse CV Events in ICH With AFib

Oral anticoagulation reduced the risk for ischemic adverse cardiovascular events in patients with atrial fibrillation (AFib) and intracranial hemorrhage (ICH), with limited effect on reducing the risk for stroke or cardiovascular death. These are the findings of a study published in The Lancet Neurology.

Adults with a prior history of ICH are at an increased risk for major adverse cardiovascular events, the highest risk being in those with concurrent AFib. Prior studies have validated oral anticoagulation as a mainstay of treatment in reducing adverse events in those with AFib, with equivocal findings when controlling for a prior history of ICH. As such, researchers investigated the effect of oral anticoagulation therapy in patients with AFib with a prior history of ICH.

The researchers conducted a prospective meta-analysis of 4 small, randomized trials.

SoSTART; ClinicalTrials.gov Identifier: NCT03153150;

APACHE-AF; ClinicalTrials.gov Identifier: NCT02565693;

NASPAF-ICH; ClinicalTrials.gov Identifier: NCT02998905; and

ELDERCARE-AF; ClinicalTrials.gov Identifier: NCT0280166).

The trials included participants whom had a history of spontaneous ICH that were assigned to either start or avoid (by placebo, open control, or another anti-thrombotic medication) long-term oral anticoagulant medication.

The primary outcome of interest was defined as any major adverse cardiovascular event, defined as any nonfatal symptomatic stroke (ischemic, hemorrhagic), or cardiovascular death. All trials recorded major adverse events between 2-6 years of follow-up.

The 4 trials included data on 412 individual participants; 310 (75%) were age 75 and older, with 249 (60%) having a CHA2DS2-VASc score of 4 or less, and 163 (40%) with a CHA2DS2-VASc score of more than 4.

Oral anticoagulation was assigned to 209 patients (130 were assigned apixaban, 61 edoxaban, 12 dabigatran, 6 rivaroxaban, and 3 warfarin). Amongst the 200 participants who were assigned to avoid oral anticoagulation, an antiplatelet agent was given to 67 (34%).

Stroke or cardiovascular death occurred in 29 (14%) of participants who initiated oral anticoagulation, compared to 43 (22%) of those who were not on treatment (pooled hazard ratio [HR], 0.68; 95% CI, 0·42–1·10; I²=0%).

Compared with no oral anticoagulation, oral anticoagulation was found to significantly reduce ischemic major adverse cardiovascular events (4% vs 19%; pooled HR, 0.27; 95% CI, 0.13–0.56; I²=0%).

Ischemic stroke was found to be the most common major adverse cardiovascular event, which was found to be less frequent in the oral anticoagulation group (4% vs 16%; pooled HR, 0.37; 95% CI, 0.17–0.83; I²=0%).

Notably, oral anticoagulation was not associated with a significant increase in hemorrhagic major adverse cardiovascular events (7% vs 5%; pooled HR, 1.80; 95% CI, 0.77–4.21; I²=0%), or death from any cause (18% vs 15%; 1·29 [0·78–2·11]; I²=50%.

Additionally, death or dependence after 1 year among patients on oral anticoagulation was found to be similar to those who were not (53% vs 51%; pooled odds ratio [OR], 1.12; 95% CI, 0.70–1.79]; I²=0%).

Study limitations included the possibility of incomplete adherence to oral anticoagulation in the trials, as well as the use of an antiplatelet agent in the comparator group, which may have limited the effect size. The sample sizes were also small and were insufficient to adequately power assessments of heterogeneity of treatment effects. “The main implication of our findings for clinical practice is that patients with spontaneous intracranial haemorrhage and atrial fibrillation can be informed that oral anticoagulation was associated with a decrease in major ischaemic cardiovascular events, and ischaemic strokes specifically, to the same extent seen for people with atrial fibrillation but no history of intracranial haemorrhage,” the researchers concluded.