Prehospital Transdermal Glyceryl Trinitrate Not Linked to Improved Stroke Outcomes

Paramedic-administered transdermal glyceryl trinitrate (GTN) before hospital admission was not associated with improvements in functional outcomes or a reduction in mortality among patients with possible stroke, according to a study published in the Lancet.

A total of 1149 patients who telephoned emergency services in the United Kingdom within 4 hours of possible stroke symptom onset were included in the phase 3 trial. Unmasked paramedics (n=516) randomly administered either once-daily 5 mg transdermal GTN for 4 days (n=568) or a similar sham dressing (n=581) to patients with presumed stroke.

The 7-level modified Rankin Scale was used to assess functional outcome at 90-day follow-up by telephone. Additional follow-up assessments included activities of daily living (Barthel Index), cognition (modified telephone Mini-Mental State Examination, Telephone Interview for Cognition Scale-modified, categorical verbal fluency), health-related quality of life (European Quality of Life-5 dimensions-3 level), and mood (abbreviated Zung depression score).

Approximately 52%, 13%, 9%, and 26% of patients had ischemic stroke, intracerebral hemorrhage, transient ischemic attack, and nonstroke mimic at final diagnosis of their initial stroke event.

Patients in the GTN group had a greater reduction in systolic blood pressure compared with the sham group (5.8 mm Hg; P <.0001). In addition, the GTN experienced a 2.6 mm Hg reduction in diastolic blood pressure at admission (P =.0026).

No difference was observed between GTN and sham patients with a final stroke or transient ischemic stroke diagnosis in terms of the 90-day modified Rankin Scale (3 [interquartile range (IQR), 2-5] vs 3 [IQR, 2-5]; adjusted odds ratio for poor outcome, 1.25; 95% CI, 0.97-1.60; P =.083).

No difference was found between the GTN group and the sham group in terms of death (36 vs 23, respectively; P =.091) or serious adverse events (188 vs 170, respectively; P =.16).

Limitations of the study include the lack of masking among paramedics, the inclusion of only patients receiving care in the United Kingdom, the relatively short follow-up, and the fact that many patients did not receive treatment for the minimum 2-day period.

Despite the lack of improvement in functional outcome and mortality in this patient population, “the study shows that large ambulance-based studies are feasible in the UK and, by extrapolation and taking into account the FAST-MAG trial, in most developed countries,” the researchers concluded.

Reference

RIGHT-2 Investigators. Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial [published online February 5, 2019]. Lancet. doi: 10.1016/S0140-6736(19)30194-1