Managed substitution of modified release nitrates with an asymmetric dosing regimen

Orally administered modified release organic nitrates are used commonly in the prophylaxis of myocardial ischaemia, although little evidence indicates a clinically superior response compared with standard formulated preparations administered symmetrically.

To investigate the clinical success of transfer of suitable patients from MR to SF nitrates.

Suitable candidates for therapeutic substitution, assessed by a pharmacist, completed a baseline study to estimate frequency and timing of chest pain, the number of rescue doses of sublingual nitrates required, together with an assessment of adverse effects experienced. Following substitution to an eccentric dosing schedule, a further one month's assessment of chest pain frequency, rescue nitrate use and adverse effects was recorded and compared with baseline.

Twelve (37.5%) patients from a possible 32 candidates were invited to complete a baseline symptoms and adverse event diary. Eight patients entered the study phase (66.7% of the 12 included in the baseline phase of the study). These candidates showed no evidence of loss of control of chest pain symptoms, 3.5 +/- 1.16 (mean +/- standard error of mean) episodes/patient/28 days compared with 1.9 +/- 0.96 episodes/patient/28 days during the test phase (P > 0.05). Similarly, there was no difference in the number of doses of rescue nitrates required when the trial phase (2.6 +/- 1.63 doses/patient/28 days) was compared with the control (2.0 +/- 1.31 doses/patient/28 days, P > 0.05). There was no evidence of an increased incidence of adverse effects during the trial period of the study.

This small study suggests that, if selected carefully, therapeutic substitution of MR oral nitrates can be managed successfully without apparent risk of loss of symptom control or increased incidence of adverse effects.