NEW YORK (Reuters Health) – Patients treated with high-dose recombinant activated factor VII (rFVIIa) for spontaneous intracerebral hemorrhage face a “small increased risk of what are usually minor cardiovascular events,” according to a report in the January issue of Stroke.

Lead author Dr. Michael N. Diringer from Washington University School of Medicine, St. Louis and his colleagues reviewed data on 841 patients enrolled in the FAST trial of rFVIIa in order to investigate the association of treatment with thromboemboli.

Just over a quarter of the patients (26.7%) experienced thromboembolic events, the authors report, including 25% in the placebo group, 22% in a group that received 20-mcg/kg rFVIIa, and 32% of patients who received 80-mcg/kg rFVIIa.

Although rates of venous events did not differ across the groups, the rate of arterial thromboembolic events was significantly higher in the 80-mcg/kg group (28%) than in the placebo group (18%) or in the 20-mcg/kg group (17%).

The frequency of myocardial infarction (ST-elevation and non-ST-elevation combined) was significantly higher with high-dose rFVIIa (12.1%) than with placebo (6.4%) or low-dose rFVIIa (7.6%).

In addition, 90-day mortality after myocardial infarction was higher in the rFVIIa groups than in the placebo group.

The frequency of cerebral ischemic events, deep vein thrombosis, and pulmonary emboli did not differ across the groups.

Besides treatment with high-dose rFVIIa, other factors that independently increased the risk of arterial thromboembolic events were signs of ischemia at baseline, increasing age, and prior use of platelet aggregation inhibitors.

“Arterial thromboembolic events, primarily myocardial events, were very common,” Dr. Diringer told Reuters Health. “The rate seems particularly high in this study since, unlike in previous studies…there was centralized EKG interpretation and troponin measurements performed on all subjects. Almost half of the events were troponin leaks without EKG changes or clinical signs.”

The authors note that the phase III FAST trial “confirmed the reduction in hematoma growth but failed to demonstrate improved outcome.”

They conclude, “Demonstration of the ability of rFVIIa to improve outcome in future studies should be driven by its effectiveness in slowing bleeding,” because that outweighs “the risk of a small increase in arterial thromboemboli.”

Reference:
Stroke 2010.