Comparative efficacy of the intravenous administration of linsidomine, a direct nitric oxide donor, and isosorbide dinitrate in severe unstable angina. A French multicentre study. French Group of Investigators.

Abstract

Although linsidomine shares common properties with nitrovasodilators, it releases nitric oxide directly without catalytic involvement by thiols. We conducted a prospective, randomized, multicentre, parallel group, single-blind study to compare the efficacy of intravenous administration of linsidomine with that of isosorbide dinitrate in unstable angina. Between November 1990 and July 1992, 568 patients with suspected unstable angina (class IIIB of the Braunwald classification) received a continuous infusion of either linsidomine (1 mg.h-1 on average) or isosorbide dinitrate (2.5 mg.h-1 on average) for 72 h. All patients received concomitant aspirin and intravenous heparin, 81% beta-blockers and 38% calcium antagonists. Holter monitoring was performed in all patients and analysed blindly. Only 25% of the patients had at least one episode of chest pain during the study (24.6% vs 25.8% in the linsidomine and isosorbide dinitrate groups, P = 0.74), of which 12% were associated with ECG changes. Holter criteria yielded similar results in both groups: 33% of patients presented episodes of myocardial ischaemia (32.6% vs 33.9% in the linsidomine and isosorbide dinitrate groups, P = 0.74), while 45% showed episodes of ventricular arrhythmia (43.5% vs 46.5% in the linsidomine and isosorbide dinitrate groups, P = 0.48). The incidence of serious clinical events at 72 h (death, myocardial infarction or myocardial revascularization) was 6.5% (5% vs 8% in the linsidomine and isosorbide dinitrate groups, P = 0.17). Intravenous linsidomine is at least as efficacious as isosorbide dinitrate in the stabilization of patients with severe unstable angina.