Glyceryl trinitrate and toe-brachial indexes in pedal ischaemia

Sylvia McAra

Research output: ThesisDoctoral Thesis

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Glyceryl trinitrate (GTN) has a long history in medicine as a safe and reliable vasodilator. However, it has not yet been established for use in peripheral arterial disease (PAD) despite low pedal blood pressures being associated with foot ulceration and amputation.

There were two primary foci of this research. The first was to determine whether GTN could ameliorate subnormal pedal blood pressure. The second was to determine whether pedal blood pressure could be measured reliably and validly via the toe brachial index (TBI) and to identify some of the characteristics of that index given that it might not only provide an accurate indication of distal pedal blood pressure but also appears to be capable of providing an early warning sign of cardiovascular disease.

The potential of GTN to redress pedal ischemia emerged after rapid healing was observed in four cases of chronic foot ulcer using GTN patches. A review of the literature indicated that GTN was associated with improvements in vascular and neurological function, particularly in warmer temperatures, so a pilot study was conducted to assess the most effective ways of measuring the relevant variables.

Subsequently, 100 people with subnormal TBIs (58 men, 42 women; mean age 69.8 years, SD = 9.5), 58% of whom were people with diabetes, completed a 6-month trial, comprising two intervention groups using 1.25 mg and 2.5 mg of GTN as Nitro-Dur (n = 33 and 24 respectively), a placebo group (n = 22), and a control group (n = 21).

Detailed analysis of TBIs was necessary as a precursor to the main analyses. This included identification of the readings that would produce the most valid single TBI, the extent to which TBIs differed between the two feet and were stable over time, and, the relationships of TBIs with demographic and health variables. The effect of GTN on TBIs was analysed per protocol using ANCOVAs. At 1 month post intervention, the high GTN dose group had significantly higher TBIs compared with both the low GTN dose group and the control group, (p = .046 and .020; effect sizes of .676 and .822 respectively). After 5 months, both GTN dose groups had significantly higher TBIs compared with the control group (p = .048 and .044; effect sizes of .531 and .662 respectively). These findings indicate that transdermal GTN at these low doses could be valuable in ameliorating pedal ischemia.

Results from the placebo group complicate these otherwise positive outcomes. Placebo group’s TBIs were between the TBIs of the other three groups at 1 month, and at that time were not significantly different from any of those three groups. However, at 5 months the placebo group was similar to both intervention groups in having higher TBIs relative to the control group (p = .006, effect size = .932).

As additional outcomes of this research, guidelines were produced for determining individual doses of GTN, and an evidence-based vascular assessment flowchart was created to enable appropriate diagnosis, referral, and stratification of risk status for PAD and cardiovascular disease.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Charles Sturt University
  • Trevethan, Robert, Advisor
  • Wang, Lexin, Principal Supervisor
  • Tinley, Paul, Principal Supervisor
Award date01 Nov 2015
Place of PublicationAustralia
Publication statusPublished - 17 Nov 2015


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