Objectives: To assess the effects of isosorbide-5-mononitrate (ISMN) in patients with microvascular angina (MVA). Methods: We randomized 20 MVA patients, treated with a β-blocker or a calcium antagonist, to 60 mg slow-release ISMN (halved to 30 mg if not tolerated) or placebo once a day for 4 weeks; the patients were then switched to the other treatment for another 4 weeks. Their clinical status was assessed with the Seattle Angina Questionnaire (SAQ) and the EuroQoL score for quality of life. The exercise stress test (EST), coronary blood flow (CBF) response to nitrate and the cold pressor test (CPT), brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) were also assessed. Results: Nine patients (45%) did not complete the ISMN phase due to side effects; 2 patients refused a follow-up. Nine patients completed the study. The SAQ and EuroQoL scores were significantly better with ISMN than with placebo, although the differences were small. No differences were found between the treatments in the EST results, CBF response to nitroglycerin (p = 0.55) and the CPT (p = 0.54), FMD (p = 0.26) and NMD (p = 0.35). Conclusions: In this study, a high proportion of MVA patients showed an intolerance to ISMN; in those tolerating the drug, significant effects on their angina status were observed, but the benefit appeared to be modest and independent of effects on coronary microvascular function.

1.
Cannon RO, Epstein SE: ‘Microvascular angina' as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol 1998;61:1338-1343.
2.
Bugiardini R, Bairey Merz CN: Angina with ‘normal' coronary arteries: a changing philosophy. JAMA 2005;293:477-484.
3.
Lanza GA: Cardiac syndrome X. A critical overview and future perspectives. Heart 2007;93:159-166.
4.
Lanza GA, Crea F: Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation 2010;121:2317-2325.
5.
Lanza GA, Colonna G, Pasceri V, Maseri A: Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X. Am J Cardiol 1999;84:854-856.
6.
Spertus JA, Winder JA, Dewhurst TA, Deyo RA, Prodzinski J, McDonell M, Fihn SD: Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol 1995;25:333-341.
7.
Stewart A: Conceptual and methodologic issues in defining quality of life: state of the art. Prog Cardiovasc Nurs 1992;7:3-11.
8.
EuroQol Group: EuroQol - a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208.
9.
Galiuto L, Sestito A, Barchetta S, Sgueglia GA, Infusino F, La Rosa C, Lanza G, Crea F: Noninvasive evaluation of flow reserve in the left anterior descending coronary artery in patients with cardiac syndrome X. Am J Cardiol 2007;99:1378-1383.
10.
Voci P, Pizzuto F, Mariano E, Puddu PE, Sardella G, Romeo F: Usefulness of coronary flow reserve measured by transthoracic coronary Doppler ultrasound to detect severe left anterior descending coronary artery stenosis. Am J Cardiol 2003;92:1320-1324.
11.
Parrinello R, Sestito A, Di Franco A, Russo G, Villano A, Figliozzi S, Nerla R, Tarzia P, Stazi A, Lanza GA, Crea F: Peripheral arterial function and coronary microvascular function in patients with variant angina. Cardiology 2014;129:20-24.
12.
Nerla R, Di Monaco A, Sestito A, Lamendola P, Di Stasio E, Romitelli F, Lanza GA, Crea F: Transient endothelial dysfunction following flow mediated dilation assessment. Heart Vessels 2011;26:524-529.
13.
Ghiadoni L, Faita F, Salvetti M, Cordano C, Biggi A, Puato M, Di Monaco A, De Siati L, Volpe M, Ambrosio G, Gemignani V, Muiesan ML, Taddei S, Lanza GA, Cosentino F: Assessment of flow mediated dilation reproducibility: a nationwide multicenter study. J Hypertens 2012;30:1399-1405.
14.
Cannon RO 3rd, Quyyumi AA, Schenke WH, Fananapazir L, Tucker EE, Gaughan AM, Gracely RH, Cattau EL Jr, Epstein SE: Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. J Am Coll Cardiol 1990;16:1359-1366.
15.
Pasceri V, Lanza GA, Buffon A, Montenero AS, Crea F, Maseri A: Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X. J Am Coll Cardiol 1998;31:62-66.
16.
Kaski JC, Rosano GMC, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA: Cardiac syndrome X: clinical characteristics and left ventricular function. Long term follow-up study. J Am Coll Cardiol 1998;31:72-76.
17.
Lamendola P, Lanza GA, Spinelli A, Sgueglia GA, Di Monaco A, Barone L, Sestito A, Crea F: Long-term prognosis of patients with cardiac syndrome X. Int J Cardiol 2010;140:197-199.
18.
Lanza GA, Manzoli A, Bia E, Crea F, Maseri A: Acute effects of nitrates on exercise testing in patients with syndrome X. Circulation 1994;90:2695-2700.
19.
Russo G, Di Franco A, Lamendola P, Tarzia P, Nerla R, Stazi A, Villano A, Sestito A, Lanza GA, Crea F: Lack of effect of nitrates on exercise stress test results in patients with microvascular angina. Cardiovasc Drugs Ther 2013;27:229-234.
20.
Janssens S: Nitric oxide for inhalation to reduce reperfusion injury in acute ST-elevation myocardial infarction (hot-line session on ‘Myocardial infarction'). Presentation ESC Congress, Barcelona, 2014.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.