Copyright © 1997 by the European Society of Cardiology.
© 1997 The European Society of Cardiology
Comparative efficacy of the intravenous administration of linsidomine, a direct nitric oxide donor, and isosorbide dinitrate in severe unstable angina
A French multicentre study
*Département Cardiovasculaire, Laboratoires Hoechst, La Défense Paris
Service de Cardiologie, Hôpital Lariboisière Paris
Service de Pharmacologie, Centre Hospitaller Régional Lille
Service de Cardiologie, Centre Hospitalier Général Saint-Germain-en-Laye
¶Unité de Soins Intensifs Cardiologiques, Centre Hospitalier Régional Lille, France
Received 21 January 1997; accepted 28 January 1997.
Correspondence: Ph. Beaufils, MD, Service de Cardiologie, Hôpital Lariboisiére, 2 rue Ambroíse Paré, 75 475 Paris Cedex 10, France
Abstract
AIMS: 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.
METHODS AND RESULTS: 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).
CONCLUSION: Intravenous linsidomine is at least as efficacious as isosorbide dinitrate in the stabilization of patients with severe unstable angina.
Key Words: Unstable angina • linsidomine • isosorbide dinitrate • Holter monitoring