-
Advances in Therapy Mar 2016Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have... (Review)
Review
INTRODUCTION
Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have suggested a link between nicorandil, gastrointestinal (GI) ulceration and fistulas. The review aims to critically appraise, synthesize and present the available evidence of all known GI ADR per anatomical location.
METHODS
The study complied with the PRISMA statement. Literature and pharmacovigilance databases were used to provide rate and/or calculate parameters (median age, median dose, history of symptoms, length of therapy and healing time after withdrawal of the drug). Differences in distribution of quantitative variables were analyzed via Mann-Whitney test. Correlation between quantitative variables was assessed with a Spearman's correlation coefficient. A p value <0.05 was significant.
RESULTS
Oral ulcerations occur in 0.2% of the subjects, anal ulcerations are present between 0.07% and 0.37% of patients. Oral and distal GI involvements are the most common ADR (28-29% and 27-31% of all GI ADR, respectively). The hepatobiliary system, the pancreas and salivary glands are not affected by nicorandil exposure. The time to develop oral ulcerations is 74 weeks among people on <30 mg/day compared to only 7.5 weeks in individuals on higher regimens (p = 0.47). There is a significant correlation between dose and ulcer healing time (Spearman's 0.525, p < 0.001).
CONCLUSIONS
Ulcerative disease is a very commonly reported GI ADR. A delayed ulcerative tendency supports the hypothesis of an ulcerogenic metabolite. Nicorandil seems to act as a cause of the ulcerations, but appears to also work in synergy with other promoting factors. Whether the action of the metabolites relies on a specific mechanism or a simple chemical ulceration is still to be established.
Topics: Aged; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Nicorandil; Oral Ulcer; Peptic Ulcer; Time Factors
PubMed: 26861848
DOI: 10.1007/s12325-016-0294-9 -
Cardiovascular Therapeutics Dec 2014It is unclear whether nicorandil, a metabolic therapeutic drug, can be applied clinically to therapy of heart failure (HF). This meta-analysis evaluated therapeutic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
It is unclear whether nicorandil, a metabolic therapeutic drug, can be applied clinically to therapy of heart failure (HF). This meta-analysis evaluated therapeutic effects of nicorandil on HF patients.
EXPERIMENTAL APPROACH
We performed a systematic review and meta-analysis of published studies evaluating effect of nicorandil on HF patients. Studies were stratified according to controlled versus uncontrolled designs and analyzed using random-effects meta-analysis models.
KEY RESULTS
We identified a total of 20 studies with a total of 1222 patients. In five randomized controlled studies, nicorandil treatment resulted in reduction in all-cause mortality and hospitalization for cardiac causes (HR: 0.35, P < 0.001) and improved cardiac pump function (SMD: 0.31, P = 0.02). In 15 observational studies, nicorandil therapy increases cardiac pump function (SMD: 0.75, P < 0.001), improves NYHA functional class (WMD: -1.33, P < 0.001), decreases PCWP (WMD: -6.86 mm Hg, P < 0.001), and pulmonary arterial pressure (SMD: -0.84, P < 0.001).
CONCLUSIONS AND IMPLICATIONS
The use of nicorandil in HF patients exerts substantial beneficial effects, suggesting that it may be an additional therapeutic agent for HF.
Topics: Blood Pressure; Coronary Circulation; Heart Failure; Heart Rate; Humans; Nicorandil; Vasodilator Agents
PubMed: 25319832
DOI: 10.1111/1755-5922.12097 -
PloS One 2013Nicorandil, as an adjunctive therapy with primary percutaneous coronary intervention (PCI), had controversial benefits in cardioprotection in patients with acute... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nicorandil, as an adjunctive therapy with primary percutaneous coronary intervention (PCI), had controversial benefits in cardioprotection in patients with acute myocardial infarction (AMI).
METHODS AND RESULTS
We performed a systematic review of randomized controlled trials (RCTs) comparing treatment with nicorandil prior to reperfusion therapy with control (placebo or no nicorandil) in patients who suffered from AMI and performed primary PCI. PubMed, EMBASE and CENTRAL databases and other sources were searched without language and publication restriction. 14 trials involving 1680 patients were included into this meta-analysis. Nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) flow grade ≤ 2 (risk ratio [RR], 0.57; 95% confidence interval [CI]: 0.42 to 0.79), the Timi frame count (TFC) (mean difference [MD], -5.19; 95% CI: -7.13 to -3.26), increased left ventricular ejection fraction (LVEF) (%) (MD, 3.08; 95% CI: 0.79 to 5.36), and reduced the incidence of ventricular arrhythmia (RR, 0.53; 95% CI: 0.37 to 0.76) and congestive heart failure (CHF) (RR, 0.41; 95% CI: 0.22 to 0.75). No difference in the pear creatine kinase (CK) value (MD, -290.19; 95% CI: -793.75 to 213.36) or cardiac death (RR, 0.39; 95% CI: 0.09 to 1.67) was observed.
CONCLUSIONS
Nicorandil prior to reperfusion is associated with improvement of coronary reflow as well as suppression of ventricular arrhythmia, and further improves left ventricular function in patients who suffered from AMI and underwent primary PCI. But the definite clinical benefits of nicorandil were not found, which may be due to the small sample size of the selected studies.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Clinical Trials as Topic; Female; Heart Failure; Humans; Male; Myocardial Infarction; Nicorandil; Percutaneous Coronary Intervention; PubMed; Risk Factors; Stroke Volume; Thrombolytic Therapy
PubMed: 24167609
DOI: 10.1371/journal.pone.0078231 -
Scientific Reports Mar 2017Many scholars have studied the effect of nicorandil on perioperative myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI), but... (Meta-Analysis)
Meta-Analysis Review
Many scholars have studied the effect of nicorandil on perioperative myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI), but results are inconsistent. Therefore, we performed this meta-analysis. Finally, 16 articles, including 1616 patients, were included into this meta-analysis. Meta-analysis results showed that: (1) Nicorandil can reduce the level of CK-MB after PCI, including at 6 hours, 12 hours, 18 hours and 24 hours. (2) Nicorandil can reduce the level of TnT after PCI, including at 6 hours, 12 hours, 18 hours and 24 hours. (3) Nicorandil can reduce the incidence of adverse reactions after PCI. (4) Nicorandil cannot reduce the level of MVP after PCI, including at 12 hours and 24 hours. (5) Subgroup analysis showed that nicorandil can reduce CK-MB and TnT level at 24 hours after PCI for Chinese's population (P < 0.05), but can not reduce CK-MB and TnT level at 24 hours after PCI for non Chinese's population (P > 0.05). Our meta-analysis indicate that nicorandil can reduce myocardial injury and reduce the incidence of adverse reaction caused by PCI for Chinese's population, but is not obvious for non Chinese's population. However, this conclusion still needs to be confirmed in the future.
Topics: Biomarkers; Cardiotonic Agents; Elective Surgical Procedures; Humans; Nicorandil; Outcome Assessment, Health Care; Percutaneous Coronary Intervention; Perioperative Care; Publication Bias; Vasodilator Agents
PubMed: 28322321
DOI: 10.1038/srep45117 -
BMC Cardiovascular Disorders Oct 2021Primary percutaneous coronary intervention is the treatment of choice in ST-segment elevation myocardial infarction and no-reflow phenomenon is still an unsolved problem. (Meta-Analysis)
Meta-Analysis
Clinical outcomes of nicorandil administration in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Primary percutaneous coronary intervention is the treatment of choice in ST-segment elevation myocardial infarction and no-reflow phenomenon is still an unsolved problem.
METHODS
We searched PubMed, EmBase, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials. The primary endpoint was the incidence of major adverse cardiac events and the secondary endpoint was the incidences of no-reflow phenomenon and complete resolution of ST-segment elevation.
RESULTS
Eighteen randomized controlled trials were enrolled. Nicorandil significantly reduced the incidence of no-reflow phenomenon (OR, 0.46; 95% CI, 0.36-0.59; P < 0.001; I = 0%) and major adverse cardiac events (OR, 0.42; 95% CI, 0.27-0.64; P < 0.001; I = 52%). For every single outcome of major adverse cardiac events, only heart failure and ventricular arrhythmia were significantly improved with no heterogeneity (OR, 0.36; 95% CI, 0.23-0.57, P < 0.001; OR, 0.43; 95% CI, 0.31-0.60, P < 0.001 respectively). A combination of intracoronary and intravenous nicorandil administration significantly reduced the incidence of major adverse cardiac events with no heterogeneity (OR, 0.24; 95% CI, 0.13-0.43, P < 0.001; I = 0%), while a single intravenous administration could not (OR, 0.66; 95% CI, 0.40-1.06, P = 0.09; I = 52%).
CONCLUSIONS
Nicorandil can significantly improve no-reflow phenomenon and major adverse cardiac events in patients undergoing primary percutaneous coronary intervention. The beneficial effects on major adverse cardiac events might be driven by the improvements of heart failure and ventricular arrhythmia. A combination of intracoronary and intravenous administration might be an optimal usage of nicorandil.
Topics: Administration, Intravenous; Aged; Coronary Circulation; Female; Humans; Male; Middle Aged; Nicorandil; No-Reflow Phenomenon; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Treatment Outcome; Vasodilator Agents
PubMed: 34629058
DOI: 10.1186/s12872-021-02301-1 -
BMC Cardiovascular Disorders Jun 2019Using the current meta-analysis as well as systematic review, to determine the curative effect of Nicorandil in comparison of no Nicorandil after elective percutaneous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Using the current meta-analysis as well as systematic review, to determine the curative effect of Nicorandil in comparison of no Nicorandil after elective percutaneous coronary intervention(PCI) on patients.
METHODS
Published literatures were identified via a computerized literature search of CENTRAL, PubMed, Cochrane, Embase Databases of Systematic Reviews. A set of randomized trials evaluating Nicorandil in comparison of no Nicorandil administered following PCI in patients harboring coronary artery disease were included. Outcomes were revealed based on the following parameters: peak creatine kinase-MB (CK-MB) value, left ventricular ejection fraction (LVEF), peak troponin I (cTnI), and major adverse cardiovascular events (MACEs) per randomized patients.
RESULTS
We included a total of 14 RCTs involving 1864 subjects in the present review. According to this meta-analysis, LVEF was significantly improved in Nicorandil group; the peak CK-MB level and the incidence of adverse cardiovascular events were remarkably lower in Nicorandil group. Nicorandil and no Nicorandil administered group appeared to be equivalent with regards to cTnI.
CONCLUSIONS
Nicorandil is effective for patients undergoing elective PCI with coronary artery disease in terms of reducing the incidence of adverse cardiovascular events as well as improving heart function. Nicorandil may exert potential role as a valid and adjunctive therapy accompanied with PCI.
Topics: Aged; Biomarkers; Cardiovascular Agents; Coronary Artery Disease; Creatine Kinase, MB Form; Female; Humans; Male; Middle Aged; Nicorandil; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recovery of Function; Stroke Volume; Treatment Outcome; Troponin I; Ventricular Function, Left
PubMed: 31200660
DOI: 10.1186/s12872-019-1071-x -
The Journal of International Medical... Nov 2020There is controversy whether nicorandil treatment has cardioprotective effects in patients with acute myocardial infarction (AMI) following percutaneous coronary... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
There is controversy whether nicorandil treatment has cardioprotective effects in patients with acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). This meta-analysis was conducted to assess the efficacy of nicorandil on functional and clinical outcomes after PCI.
METHODS
Systematic databases were searched to retrieve studies that compared the effect of nicorandil with a control group in patients with AMI who underwent PCI. Outcomes related to coronary blood flow, and functional and clinical outcomes were extracted and a meta-analysis was performed. Trial sequential analysis was conducted to estimate the required sample size for statistical power.
RESULTS
Twenty-four trials involving 2965 patients with AMI were enrolled. Pooled results showed that nicorandil treatment significantly suppressed the incidence of no-reflow phenomenon and reperfusion arrhythmia after reperfusion, improved the left ventricular ejection fraction and left ventricular end-systolic volume index, and reduced major adverse cardiovascular events and cardiovascular death. Trial sequential analysis confirmed the effect of nicorandil in reducing the incidence of no-reflow phenomenon and follow-up major adverse cardiovascular events in patients with AMI after PCI.
CONCLUSION
Our findings suggest that nicorandil treatment adjunctive to reperfusion therapy improves myocardial reperfusion, cardiac function, and clinical outcomes in patients with AMI.
Topics: Humans; Myocardial Infarction; Nicorandil; Percutaneous Coronary Intervention; Stroke Volume; Ventricular Function, Left
PubMed: 33249959
DOI: 10.1177/0300060520967856 -
European Heart Journal Jan 2019Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy...
Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy with drugs classified as being first line (beta blockers, calcium channel blockers, short acting nitrates) or second line (long-acting nitrates, ivabradine, nicorandil, ranolazine, and trimetazidine). Second line drugs are indicated for patients who have contraindications to first line agents, do not tolerate them or remain symptomatic. Evidence that one drug is superior to another has been questioned. Between January and March 2018, we performed a systematic review of articles written in English over the past 50 years English-written articles in Medline and Embase following preferred reporting items and the Cochrane collaboration approach. We included double blind randomized studies comparing parallel groups on treatment of angina in patients with stable coronary artery disease, with a sample size of, at least, 100 patients (50 patients per group), with a minimum follow-up of 1 week and an outcome measured on exercise testing, duration of exercise being the preferred outcome. Thirteen studies fulfilled our criteria. Nine studies involved between 100 and 300 patients, (2818 in total) and a further four enrolled greater than 300 patients. Evidence of equivalence was demonstrated for the use of beta-blockers (atenolol), calcium antagonists (amlodipine, nifedipine), and channel inhibitor (ivabradine) in three of these studies. Taken all together, in none of the studies was there evidence that one drug was superior to another in the treatment of angina or to prolong total exercise duration. There is a paucity of data comparing the efficacy of anti-anginal agents. The little available evidence shows that no anti-anginal drug is superior to another and equivalence has been shown only for three classes of drugs. Guidelines draw conclusions not from evidence but from clinical beliefs.
Topics: Adrenergic beta-Antagonists; Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Humans; Nitrates; Randomized Controlled Trials as Topic
PubMed: 30165445
DOI: 10.1093/eurheartj/ehy504 -
International Heart Journal Jul 2019Current studies demonstrating the effects of nicorandil in the prognosis of coronary artery disease (CAD) patients who received percutaneous coronary intervention (PCI)... (Meta-Analysis)
Meta-Analysis
Current studies demonstrating the effects of nicorandil in the prognosis of coronary artery disease (CAD) patients who received percutaneous coronary intervention (PCI) are inconclusive due to the small sample size and small events rate.PubMed, OVID, CBM and CNKI databases were searched using a pre-specified search string to collect randomized controlled trials (RCTs) studying the effects of nicorandil on CAD patients receiving PCI. Data on all-cause mortality and cardiovascular events were collected. RevMan 5.3 software was used for meta-analysis. Subgroup analysis was conducted in patients receiving primary PCI (PPCI) and elective PCI (EPCI).A total of 18 RCTs were included in our final analysis. Nicorandil treatment significantly reduced total mortality in PPCI (Peto OR = 0.44, 95%CI 0.25-0.79, P = 0.006) and EPCI (Peto OR = 0.41, 95%CI 0.25-0.67, P = 0.0004), cardiovascular death in both PPCI (Peto OR = 0.41, 95%CI 0.20-0.84, P = 0.01) and EPCI (Peto OR = 0.40, 95%CI 0.20-0.80, P = 0.009), and heart failure in PPCI (RR = 0.36, 95%CI 0.22-0.59, P < 0.0001). When compared with placebo plus standard treatment or standard treatment alone, nicorandil plus standard treatment was associated with reduced total mortality in both PPCI and EPCI, CV death in EPCI, and heart failure in PPCI. Nicorandil is associated with lower risks of total mortality and CV death in PPCI and EPCI in those who received nicorandil > 28 days.Nicorandil as an adjunct therapy along with PCI is associated with reduced total mortality and cardiovascular death in PPCI and EPCI patients, and reduced heart failure in PPCI patients.
Topics: Cause of Death; Coronary Artery Disease; Global Health; Humans; Nicorandil; Percutaneous Coronary Intervention; Prognosis; Survival Rate; Vasodilator Agents
PubMed: 31308321
DOI: 10.1536/ihj.18-337 -
Medicine Sep 2020The prevalence of cardiac syndrome X (CSX) is considerable. Some patients show recurrent angina attacks and have a poor prognosis. However, the knowledge of CSX... (Meta-Analysis)
Meta-Analysis
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 = 20%, P < .00001), resting ECG (RR = 1.24, 95% IC: 1.15 to 1.33, I = 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 = 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 = 77%, P < .00001) and increase the level of nitric oxide (NO) (WMD = 27.45, 95% IC: 125.65 to 29.24, I = 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.
Topics: Electrocardiography; Endothelin-1; Endothelium, Vascular; Exercise Test; Humans; Microvascular Angina; Nicorandil; Nitric Oxide; Randomized Controlled Trials as Topic; Vasodilator Agents
PubMed: 32925783
DOI: 10.1097/MD.0000000000022167