Comparison of the Efficacy of Isosorbide Dinitrate Spray and Nitroglycerin Spray in the Regression of Symptoms of Exercise-Induced Moderate Angina Pectoris

Abstract

This single-centre, controlled, randomised, double-blind, crossover trial was carried out to evaluate the time to recovery from angina pectoris after application of an isosorbide dinitrate (ISDN) spray formulation, which was developed a few years ago (Isoket® spray, Schwarz Pharma, Monheim, Germany), in comparison with that with nitroglycerin (NG) spray in patients with chronic stable angina with documented coronary artery disease. A secondary objective of this trial was to evaluate the safety and tolerability of ISDN spray. 65 patients were randomised to this study; 62 patients were evaluated for efficacy in the intent-to-treat analysis and 28 patients could be evaluated for the per-protocol analysis. Considering the pooled data of the intent-to-treat analysis, patients receiving ISDN spray (2 squirts of 1.25mg ISDN each) recovered after 67.16 seconds, compared with patients administered NG spray treatment (2 squirts of 0.4mg NG each) who recovered after 74.11 seconds (mean difference 6.95 seconds). The Moses 90% confidence interval clearly indicated that the two treatments were equivalent with regard to the clinically relevant difference of 30 seconds as defined in the protocol. In the per-protocol analysis, the pooled data demonstrated that the mean time to recovery from angina pectoris was 63.86 seconds in the ISDN spray-treated patients compared with 71.14 seconds in the NG spray-treated patients. This analysis also indicated that the treatments were equivalent with regard to the clinically relevant difference of 30 seconds as defined in the protocol (Moses 90% confidence interval). In the intent-to-treat analysis the global evaluation of efficacy showed that the investigator rated ISDN spray to be ‘very good’ or ‘good’ in 55 cases and NG spray to be ‘very good’ or ‘good’ in 54 cases. In 56 cases in the ISDN spray group and in 55 cases in the NG spray group treatment was classified as ‘very good’ or ‘good’ by the patients. Comparable results were obtained in the per-protocol analysis. Four adverse events were reported: 2 cases of orthostatic hypotension occurred during the nitrate response test, and 2 patients developed ventricular arrhythmia. In all cases the investigators denied any relationship to the study medication.