Withdrawal of intravenous glyceryl trinitrate: absence of rebound phenomena with transition to oral isoborbide dinitrate

Abstract

1. Glyceryl trinitrate (GTN) is frequently infused intravenously as a component of the management of acute coronary syndromes (ACS). Abrupt cessation of GTN infusion after periods of more than 24 h administration often induces rebound vasoconstriction reflecting ‘pseudotolerance’; this is also the basis of the ‘zero hour phenomenon’ during chronic nitrate therapy. The efficacy of oral nitrate regimens to prevent vasoconstriction following cessation of intravenous GTN has not been previously examined. Therefore, we investigated the effects of transition from intravenous GTN to oral isosorbide dinitrate (ISDN) on a parameter of apparent arterial stiffness in patients with ACS. 2. The effects of GTN infusion at 5 μg/min on augmentation index (AIx) were quantified in patients ( n = 10) with stable angina pectoris in order to establish the magnitude of effect on apparent arterial stiffness. 3. This infusion rate of GTN reduced AIx from 23 ± 10% (SD) to 3 ± 14% (SD) ( P < 0.01). The effect of transition from GTN infusion of greater than 24 h duration to ISDN (10 mg tds) were examined in patients ( n = 16) with ACS (unstable angina/non-Q-wave myocardial infarction). No patient developed recurrent angina during the 24 h following cessation of GTN infusion. The level of AIx was 8 ± 4% (SD) prior to GTN cessation and fell to 5 ± 6% (SD) on ISDN ( P = 0.05). 4. Thus, in patients treated for ACS, transition from intravenous GTN to low dose oral ISDN is associated with an incremental vasodilatation and no evidence of ‘rebound’ ischaemia.