Poor Tolerance and Limited Effects of Isosorbide-5-Mononitrate in Microvascular Angina

Abstract

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.

Poor Tolerance and Limited Effects of Isosorbide-5-Mononitrate in Microvascular Angina

“…A statistically significant improvement in quality of life was demonstrated in patients who continued the nitrate treatment. However, this improvement was not confirmed by the results of the exercise stress test or in the coronary microvascular and peripheral vascular function measurements [14] . Similar results for vascular functions and exercise stress tests have been reported with the sublingual administration of short-acting nitrates [15,16] .…”

“…Data on the effect of long-acting nitrates in the current literature are scarce; in the study by Lanza et al [13] , isosorbide-5-mononitrate was found to not be effective in controlling episodes of chest pain in patients with with the addition of isosorbide-5-mononitrate is important. However, due to a small study population and a high discontinuation rate of nitrate administration, the findings by Wu et al [14] on the clinical implication of routine use of long-acting nitrates in microvascular angina are questionable. More evidence is necessary to evaluate whether long-acting nitrates may become a routine medical approach for microvascular angina patients whose symptoms are not adequately controlled by first-line drug therapy.…”

“…In this issue of Cardiology , Wu et al [14] explored the role of slow-release, long-acting nitrates as an additional therapy for patients with microvascular angina. The quality of life, exercise stress test results and coronary microvascular and peripheral vascular functions of patients were evaluated.…”

“…Evaluating the effect of slow-release isosorbide-5-mononitrate only in the short term was another limitation of the study by Wu et al [14] . Nitrate tolerance is a major limitation for their chronic use [1] .…”

NO and HNO donors, nitrones, and nitroxides: Past, present, and future

“…It can cause a significant reduction in angina frequency, when compared to GTN, with complete eradication of acute angina episodes . However, ISMN showed reduced efficiency and tolerance rate in microvascular angina . These shortcomings have been associated with endothelial dysfunction and oxidative stress …”