Alexander E. Merkler, MD

Krishnan K, Scutt P, Woodhouse L, Adami A, Becker JL, Berge E, et al. Glyceryl Trinitrate for Acute Intracerebral Hemorrhage: Results From the Efficacy of Nitric Oxide in Stroke (ENOS) Trial, a Subgroup Analysis. Stroke. 2016

Outcomes in patients with intracerebral hemorrhage (ICH) are poor; more than two-thirds of survivors with ICH are left disabled at three months and less than half of patients with ICH are alive at 1 year. Ongoing research continues to address ways to improve outcomes – one such approach is acute blood pressure reduction. High blood pressure is common in acute ICH and is associated with worse outcomes, at least in part through hematoma expansion. Previous trials such as INTERACT have shown a trend towards improved functional outcomes using intensive BP lowering within the first 6 hours after ICH, but management of high BP in acute ICH remains uncertain.

The current subgroup analysis of the ENOS (Efficacy of Nitric Oxide in Stroke) trial evaluates the impact of transdermal glyceryl trinitrate (GTN) in patients with ICH. ENOS was a large multicenter trial that evaluated BP reduction in patients with both ischemic stroke and ICH using GTN. When GTN was given within 48 hours of stroke onset, BP was significantly reduced at day 1; however, functional outcome at 90 days was no different. When GTN was given within six hours of stroke though, functional outcomes were improved. In this current manuscript, the authors performed a pre-specified subgroup analysis, evaluating whether use of GTN in patients with ICH improved functional outcomes both overall, and within 6 hours of having an ICH.

629 patients with ICH presenting within 48 hours and initial SBP >140mmHg were included. Patients were randomized to receive GTN transdermally for one week versus no GTN. The mean time to randomization was 25 hours. 87% of hemorrhages were deep and 26% of patients had IVH. BP was significantly lower following the first dose of GTN versus no GTN (7.5/4.2 mmHg).

Overall, at 90 days, the median mRS was the same (3) in both the GTN and no GTN groups. In addition, there were no differences between secondary outcomes such as measures of disability, cognition, mood and quality of life. No differences in serious adverse events were seen.

Of the 61 (9.7%) patients randomized within 6 hours (and in whom the average time to treatment was 4.4 hours), patients randomized to GTN had an improved functional outcome as manifested by a positive shift on the mRS, improved mood and quality of life and reduced death.

GTN is a useful transdermal agent to acutely lower BP and does not seem to have serious adverse effects. The study adds further support that early BP lowering in patients with ICH may improve functional outcomes.