The effect of nicorandil in patients with cardiac syndrome X

Abstract

Background: The prevalence of cardiac syndrome X (CSX) is considerable. Some patients show recurrent angina attacks and have a poor prognosis. However, the knowledge of CSX pathophysiological mechanism is still limited, and the treatment fails to achieve a satisfactory suppression of symptoms. Nicorandil has a beneficial effect on improving coronary microvascular dysfunction (CMD). This study aims to evaluate the clinical effects and safety of nicorandil on CSX patients. Methods: The Cochrane Library, Pubmed, EMBASE, ClinicalTrials.gov and 4 Chinese databases were searched to identify relevant studies. The Cochrane “Risk of bias” tool was used to assess the methodological quality of eligible studies. Meta-analysis was performed by RevMan 5.3 software. The Eggers test and meta-regression were performed by software Stata 14.0. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Twenty four randomized controlled trials (RCTs) involving 2323 patients were included. Most of the included studies were classified as having an unclear risk of bias because of poor reported methodology. The main outcomes are angina symptoms improvement, resting electrocardiogram (ECG) improvement, treadmill test result, and endothelial function. Meta-analysis showed that nicorandil had some benefit on improving angina symptoms (RR 1.24, 95% CI 1.19 to 1.29, I 2 = 20%, P < .00001), resting ECG (RR = 1.24, 95% IC: 1.15 to 1.33, I 2 = 0%, P < .00001), and prolonged the time to 1 mm ST-segment depression in treadmill test result (WMD = 38.41, 95% IC: 18.46 to 58.36, I 2 = 0%, P = .0002). Besides nicorandil could reduce the level of endothelin-1 (ET-1) (SMD = −2.22, 95% IC: −2.61 to −1.83, I 2 = 77%, P < .00001) and increase the level of nitric oxide (NO) (WMD = 27.45, 95% IC: 125.65 to 29.24, I 2 = 81%, P < .00001). No serious adverse drug event was reported. The Eggers test showed that significant statistical publication bias was detected (Eggers test P = .000). The quality of evidence ranged from very low to low. Conclusions: Nicorandil shows the potential of improving angina symptoms, ECG, and endothelial dysfunction in patients with CSX. However, there is insufficient evidence for the clinical benefits of nicorandil due to the very low-quality evidence.

Contemporary pharmacological treatment strategies for patients with angina and unobstructed coronary arteries (ANOCA) due to coronary microvascular dysfunction

“…A small randomized study by Zhang et al [63] found significant improvement in CFR after treatment with a combination of fluvastatin and diltiazem compared with fluvastatin or diltiazem alone in patients with angina pectoris and normal epicardial arteries on angiogram. Another randomized study by Yokoyama et al [64] described significant improvement from baseline CFR after treatment with simvastatin but not pravastatin in patients with high cholesterol and a low likelihood of CAD. Based on these studies, the use of statins is recommended for most patients with CMD but especially for the endotype of impaired vasodilation unless severe side effects or contraindications are present.…”

Coronary Microvascular Angina: A State-of-the-Art Review

“…Nicorandil, ivabradine, and trimetazidine are drugs under investigation to evaluate their potential role in the treatment of CMD. Nicorandil is a mitochondrial ATP-sensitive potassium channel activator that showed some effects in improving symptoms ( 54 ). A study demonstrated that ivabradine, which selectively reduces sinus node activity, could improve angina in patients with CMD, but without effects on CFR ( 55 ).…”

Updates on Pharmacologic Management of Microvascular Angina

“…Finally, a recent meta-analysis on the effects of nicorandil on MVA patients showed its potential of improving angina symptoms, ECG, and endothelial dysfunction. However, due to low-quality evidence among analyzed studies, clinical benefits remained unclear [185].…”