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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 -
Indian Journal of Pharmacology 2019Nicorandil is a well-known antianginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European... (Review)
Review
Nicorandil is a well-known antianginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European guidelines. It shows an efficacy equivalent to that of classic antianginal agents. Nicorandil has also been applied clinically in various cardiovascular diseases such as variant or unstable angina and reperfusion-induced damage following coronary angioplasty or thrombolysis. Different mechanisms have been involved in the protective effects of nicorandil in various diseases through either opening of adenosine triphosphate-sensitive potassium (KATP) channel or donation of nitric oxide (NO). The predominance or participation of any of these proposed mechanisms depends on the dose of nicorandil used, the location of diseased conditions, and if this mechanism is still functioning or not. The protection afforded by nicorandil has been shown to be mainly attributed to KATP channel opening in experimental models of myocardial and pulmonary fibrosis as well as renal injury or glomerulonephritis, whereas NO donation predominates as a mechanism of protection in hepatic fibrosis and inflammatory bowel diseases. Therefore, in different diseased conditions, it is important to know which mechanism plays the major role in nicorandil-induced curative or protective effects. This can bring new insights into the proper use of selected medication and its recommended dose for targeting certain disease.
Topics: Angina, Stable; Animals; Anti-Arrhythmia Agents; Dose-Response Relationship, Drug; Humans; KATP Channels; Nicorandil; Nitric Oxide; Nitric Oxide Donors
PubMed: 31831918
DOI: 10.4103/ijp.IJP_298_19 -
World Journal of Emergency Medicine 2020This study investigated the effects of the intracoronary injection of nicorandil and tirofiban on myocardial perfusion and short-term prognosis in elderly patients with...
Effects of intracoronary injection of nicorandil and tirofiban on myocardial perfusion and short-term prognosis in elderly patients with acute ST-segment elevation myocardial infarction after emergency PCI.
BACKGROUND
This study investigated the effects of the intracoronary injection of nicorandil and tirofiban on myocardial perfusion and short-term prognosis in elderly patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI).
METHODS
Seventy-eight STEMI patients with age >65 years who underwent emergency PCI were consecutively enrolled. These patients received conventional PCI and were randomly divided into a control group and a treatment group (=39 per group). The control group received an intracoronary injection of tirofiban followed by a maintenance infusion for 36 hours after surgery. The treatment group received intracoronary injection of tirofiban and nicorandil, and then intravenous infusion of tirofiban and nicorandil 36 hours after surgery. The following parameters were measured: TIMI grade, corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), ST-segment resolution (STR) rate 2 hours post-operatively, resolution of ST-segment elevation (STR) at 2 hours postoperatively, peak level of serum CK-MB, left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) at 7-10 days postoperatively, and major adverse cardiac events (MACEs) in-hospital and within 30 days post-operatively.
RESULTS
Compared with the control group, more patients in the treatment group had TIMI 3 and TMPG 3, and STR after PCI was significantly higher. The treatment group also had significantly lower cTFC, lower infarction relative artery (IRA), lower peak CK-MB, and no reflow ratio after PCI. The treatment group had significantly higher LVEDD and LVEF but lower incidence of MACEs than the control group.
CONCLUSION
The intracoronary injection of nicorandil combined with tirofiban can effectively improve myocardial reperfusion in elderly STEMI patients after emergency PCI and improve short-term prognoses.
PubMed: 32351648
DOI: 10.5847/wjem.j.1920-8642.2020.03.005 -
Evidence-based Complementary and... 2022Nicorandil has been widely used for the treatment of angina pectoris and myocardial infarction. The purpose of this study was to investigate whether nicorandil plays a...
OBJECTIVE
Nicorandil has been widely used for the treatment of angina pectoris and myocardial infarction. The purpose of this study was to investigate whether nicorandil plays a protective role in exhaustive exercise (EE)-induced myocardial injury.
METHODS
Here, we applied the rat EE model and treated them with exercise preconditioning (EP, reported to protect the heart) or different doses of nicorandil gavage, respectively, to explore whether there are protective effects of single EP or nicorandil or a combination of both and the potential mechanism. Forty-nine male Sprague Dawley rats were randomly divided into control, EE, EP + EE, nicorandil (with low, middle, and high dose) + EE, and EP + nicorandil (middle dose) + EE. Blood samples and myocardial tissues were collected to analyze the myocardial injury-related index.
RESULTS
EE induced myocardial structural damage and altered the myocardial injury markers, which were partially reversed by pretreatment of nicorandil. In addition, oxidative stress and inflammation lead to the accumulation of reactive oxygen species (ROS) products and further damage to the myocardium, while pretreatment of nicorandil reduces the oxidative stress response and inflammation. Moreover, nicorandil suppressed the myocardial apoptosis induced by EE, as indicated by a decrease of Bax and caspase-3 expression and an increase of Bcl-2 expression. Finally, the pathway in which nicorandil plays a role may be involved in the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Pretreatment of nicorandil increased the protein level of myocardial eNOS and NO production.
CONCLUSION
Our result demonstrated that nicorandil has protective effects in EE-induced myocardial injury with dose-dependent effects. A combination of nicorandil and EP can further improve the protective effects. Taken together, nicorandil can be potentially used as an intervention method in EE-induced myocardial injury.
PubMed: 35035509
DOI: 10.1155/2022/7550872 -
PeerJ 2022This study aimed to conduct a network meta-analysis (NMA) to compare the efficacy of brain natriuretic peptide (BNP) vs nicorandil for preventing contrast-induced... (Meta-Analysis)
Meta-Analysis
This study aimed to conduct a network meta-analysis (NMA) to compare the efficacy of brain natriuretic peptide (BNP) vs nicorandil for preventing contrast-induced nephropathy (CIN). Databases of Pubmed, Cochrane, Embase, Web of Science were searched by keywords for eligible studies of randomized controlled trials investigating different agents (BNP, nicorandil, nitroglycerin, intravenous saline) for preventing CIN. The outcomes included a change in serum creatinine level at 48 h and the incidence of CIN after percutaneous coronary intervention (PCI) or coronary angiography (CAG). A total of 13 studies with 3,462 patients were included. Compared with intravenous saline alone, except for nitroglycerin (odds ratio [OR]: 1.02, 95% CI [0.36-2.88]), the other drugs significantly reduced the CIN incidence with OR of 0.35 (95% CI [0.24-0.51]) for BNP, 0.52 (0.29, 0.94) for usual-dose nicorandil, 0.28 (0.19, 0.43) for double-dose nicorandil. BNP and double-dose nicorandil significantly decreased the change of serum creatinine (SCr) levels with mean difference (MD) of -6.98, (-10.01, -3.95) for BNP, -8.78, (-11.63, -5.93) for double-dose nicorandil. No significant differences were observed in the change of SCr levels for nitroglycerin (-4.97, [-11.46, 1.52]) and usual-dose nicorandil (-2.32, [-5.52, 0.89]) compared with intravenous saline alone. For double-dose nicorandil, the CIN incidence and the change of SCr level in group of 4-5 days treatment course were more than group of less than or equal to 24 h treatment course (OR of 1.48, [0.63-3.46] and MD of 2.48, [-1.96, 6.91]). In conclusion, BNP and double-dose nicorandil can have effects on preventing the incidence of CIN and double-dose nicorandil performed better than BNP. In double-dose nicorandil groups, a course of less than or equal to 24 h before and after procedure performed with better efficacy than a course of 4-5 days.
Topics: Humans; Nicorandil; Natriuretic Peptide, Brain; Contrast Media; Nitroglycerin; Percutaneous Coronary Intervention; Network Meta-Analysis; Creatinine; Kidney Diseases
PubMed: 35228908
DOI: 10.7717/peerj.12975 -
Trials Jul 2021The pathophysiology of SARS-Cov-2 is characterized by inflammation, immune dysregulation, coagulopathy, and endothelial dysfunction. No single therapeutic agent can...
A randomized open-label trial to evaluate the efficacy and safety of triple therapy with aspirin, atorvastatin, and nicorandil in hospitalised patients with SARS Cov-2 infection: A structured summary of a study protocol for a randomized controlled trial.
OBJECTIVES
The pathophysiology of SARS-Cov-2 is characterized by inflammation, immune dysregulation, coagulopathy, and endothelial dysfunction. No single therapeutic agent can target all these pathophysiologic substrates. Moreover, the current therapies are not fully effective in reducing mortality in moderate and severe disease. Hence, we aim to evaluate the combination of drugs (aspirin, atorvastatin, and nicorandil) with anti-inflammatory, antithrombotic, immunomodulatory, and vasodilator properties as adjuvant therapy in covid- 19.
TRIAL DESIGN
Single-centre, prospective, two-arm parallel design, open-label randomized control superiority trial.
PARTICIPANTS
The study will be conducted at the covid centre of Dr. Rajendra Prasad Government Medical College Tanda Kangra, Himachal Pradesh, India. All SARS-CoV-2 infected patients requiring admission to the study centre will be screened for the trial. All patients >18years who are RT-PCR/RAT positive for SARS-CoV-2 infection with pneumonia but without ARDS at presentation (presence of clinical features of dyspnoea hypoxia, fever, cough, spo2 <94% on room air and respiratory rate >24/minute) requiring hospital admission and consenting to participate in the trial will be included. Patients with documented significant liver disease/dysfunction (AST/ALT > 240), myopathy and rhabdomyolysis (CPK > 5x normal), allergy or intolerance to statins, allergy or intolerance to aspirin, patients taking medications with significant interaction with statins, prior statin use (within 30 days), prior aspirin use (within 30 days), history of active GI bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, patient unable to take oral or nasogastric medications, patients in altered mental status, shock, acute renal failure, acute coronary syndrome, sepsis and ARDS at presentation will be excluded.
INTERVENTION AND COMPARATOR
After randomization, participants in the intervention group will receive aspirin, atorvastatin, and nicorandil (Fig. 1). Atorvastatin will be prescribed as 40 mg starting dose followed by 40 mg oral tablets once daily for ten days or till hospital discharge whichever is later. Aspirin dose will be 325 starting dose followed by 75 mg once daily for ten days or till hospital discharge whichever is later. Nicorandil will be given as 10 mg starting dose followed by 5mg twice daily ten days or till hospital discharge whichever is later. All patients in the intervention and control group will receive a standard of care for covid management as per national guidelines. All patients will receive symptomatic treatment with antipyretics, adequate hydration, anticoagulation with low molecular weight heparin, intravenous remdesivir, corticosteroids (intravenous dexamethasone for 5 days or more duration if oxygen requirement increasing or inflammatory markers are raised), and oxygen support. Patients will receive treatment for comorbid conditions as per guidelines. Fig. 1 Schematic study design MAIN OUTCOMES: The patients will be followed up for outcomes during the hospital stay or for ten days whichever is longer. The primary outcome will be in-hospital mortality. Any progression to ARDS, shock, acute kidney injury, impaired consciousness, length of hospital stay, length of mechanical ventilation (invasive plus non-invasive) will be secondary outcomes. Changes in serum markers (CRP, D -dimer, S ferritin) will be other secondary outcomes. The safety endpoints will be hepatotoxicity (ALT/AST > 3x ULN; hyperbilirubinemia), myalgia-muscle ache, or weakness without creatine kinase (CK) elevation, myositis-muscle symptoms with increased CK levels (3-10) ULN, rhabdomyolysis-muscle symptoms with marked CK elevation (typically substantially greater than 10 times the upper limit of normal [ULN]) and with creatinine elevation (usually with brown urine and urinary myoglobin) observed during the hospital stay.
RANDOMIZATION
Computer-generated block randomization will be used to randomize the participants in a 1:1 ratio to the active intervention group A (Aspirin, Atorvastatin, Nicorandil) plus conventional therapy and control group B conventional therapy only.
BLINDING (MASKING)
The study will be an open-label trial.
NUMBERS TO BE RANDOMIZED (SAMPLE SIZE)
A total of 396 patients will participate in this study, which is randomly divided with 198 participants in each group.
TRIAL STATUS
The first version of the protocol was approved by the institutional ethical committee on 1 February 2021, IEC /006/2021. The recruitment started on 8/4/2021 and will continue until 08/07/2021. A total of 281 patients have been enrolled till 21/5/2021.
TRIAL REGISTRATION
The trial has been prospectively registered in Clinical Trial Registry - India (ICMR- NIMS): CTRI/2021/04/032648 [Registered on: 8 April 2021].
FULL PROTOCOL
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported under the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.
Topics: Aspirin; Atorvastatin; COVID-19; Humans; India; Nicorandil; Prospective Studies; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome
PubMed: 34266452
DOI: 10.1186/s13063-021-05361-y -
BMC Cardiovascular Disorders Jun 2021Duchenne muscular dystrophy (DMD) associated cardiomyopathy is a major cause of morbidity and mortality. In an in vitro DMD cardiomyocyte model, nicorandil reversed...
BACKGROUND
Duchenne muscular dystrophy (DMD) associated cardiomyopathy is a major cause of morbidity and mortality. In an in vitro DMD cardiomyocyte model, nicorandil reversed stress-induced cell injury through multiple pathways implicated in DMD. We aimed to test the efficacy of nicorandil on the progression of cardiomyopathy in mdx mice following a 10-day treatment protocol.
METHODS
A subset of mdx mice was subjected to low-dose isoproterenol injections over 5 days to induce a cardiac phenotype and treated with vehicle or nicorandil for 10 days. Baseline and day 10 echocardiograms were obtained to assess cardiac function. At 10 days, cardiac tissue was harvested for further analysis, which included histologic analysis and assessment of oxidative stress. Paired student's t test was used for in group comparison, and ANOVA was used for multiple group comparisons.
RESULTS
Compared to vehicle treated mice, isoproterenol decreased ejection fraction and fractional shortening on echocardiogram. Nicorandil prevented isoproterenol induced cardiac dysfunction. Isoproterenol increased cardiac fibrosis, which nicorandil prevented. Isoproterenol increased gene expression of NADPH oxidase, which decreased to baseline with nicorandil treatment. Superoxide dismutase 2 protein expression increased in those treated with nicorandil, and xanthine oxidase activity decreased in mice treated with nicorandil during isoproterenol stress compared to all other groups.
CONCLUSIONS
In conclusion, nicorandil is cardioprotective in mdx mice and warrants continued investigation as a therapy for DMD associated cardiomyopathy.
Topics: Animals; Cardiomyopathies; Disease Models, Animal; Female; Fibrosis; Isoproterenol; Mice, Inbred mdx; Muscular Dystrophy, Duchenne; Myocytes, Cardiac; NADPH Oxidases; Nicorandil; Reactive Oxygen Species; Stroke Volume; Superoxide Dismutase; Ventricular Function, Left; Xanthine Oxidase; Mice
PubMed: 34130633
DOI: 10.1186/s12872-021-02112-4 -
Biomedicine & Pharmacotherapy =... Jul 2020Nicorandil exerts a protective effect against coronary microvascular dysfunction in acute myocardial infarction (AMI) patients. However, the mechanism and effect of...
OBJECTIVE
Nicorandil exerts a protective effect against coronary microvascular dysfunction in acute myocardial infarction (AMI) patients. However, the mechanism and effect of nicorandil in hyperhomocysteinemia (HHcy) AMI patients remain unclear.
METHODS
C57/BL6 mice with mild to moderate HHcy and human coronary artery endothelial cells (HCAECs) cotreated with HHcy (1 mmol/L) for 24 h and hypoxia for 6 h were selected as models. Small animal ultrasound detection was used to compare cardiac function. CD31 immunofluorescence staining and tomato lectin staining were used to assess the number of microcirculation changes in vivo. MTT, tube formation and western blotting assays were used to evaluate the effect of nicorandil on HCAECs and the PI3K/Akt/eNOS pathway.
RESULTS
The results showed that nicorandil improved cell viability and p-PI3K/PI3K, p-Akt/Akt, and p-eNOS/eNOS expression in the vitro HHcy and hypoxia models. The beneficial effects of nicorandil on HCAECs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the nitric oxide synthase (NOS) inhibitor L-NAME. In vivo, nicorandil improved the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the post-HHcy + MI model, and the levels of CD31 and tomato lectin expression were higher in the nicorandil treatment group. The effectiveness of nicorandil was inhibited in the PI3K and L-NAME groups.
CONCLUSION
The results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway.
Topics: Animals; Cell Survival; Cells, Cultured; Chromones; Endothelial Cells; Homocysteine; Humans; Hyperhomocysteinemia; Hypoxia; Male; Mice; Microcirculation; Morpholines; Myocardial Infarction; NG-Nitroarginine Methyl Ester; Nicorandil; Nitric Oxide Synthase Type III; Phosphatidylinositol 3-Kinases; Plant Lectins; Platelet Endothelial Cell Adhesion Molecule-1; Proto-Oncogene Proteins c-akt; Ventricular Function, Left
PubMed: 32407984
DOI: 10.1016/j.biopha.2020.110121 -
Biomedicines Jan 2021Nicorandil, a balanced vasodilator, is used in the second-line therapy of angina pectoris. In this study, we aimed to illuminate the effects of nicorandil on...
Nicorandil, a balanced vasodilator, is used in the second-line therapy of angina pectoris. In this study, we aimed to illuminate the effects of nicorandil on inflammation, apoptosis, and atherosclerotic plaque progression. Twenty-five LDL-R -/- mice were fed a high-fat diet for 14 weeks. After 6 weeks mice were randomly allocated to treatment with nicorandil (10 mg/kg/day) or tap water. Nicorandil treatment led to a more stable plaque phenotype, displaying an increased thickness of the fibrous cap ( = 0.014), a significant reduction in cholesterol clefts ( = 0.045), and enhanced smooth muscle cell content ( = 0.009). In endothelial cells nicorandil did not reduce the induction of adhesion molecules or proinflammatory cytokines. In HO challenged endothelial cells, pretreatment with nicorandil significantly reduced the percentage of late apoptotic/necrotic cells ( = 0.016) and the ratio of apoptotic to living cells ( = 0.036). Atherosclerotic lesions of animals treated with nicorandil exhibited a significantly decreased content of cleaved caspase-3 ( = 0.034), lower numbers of apoptotic nuclei ( = 0.040), and reduced 8-oxogunanine staining ( = 0.039), demonstrating a stabilizing effect of nicorandil in established atherosclerotic lesions. We suggest that nicorandil has a positive effect on atherosclerotic plaque stabilization by reducing apoptosis.
PubMed: 33513743
DOI: 10.3390/biomedicines9020120 -
Alternative Therapies in Health and... Mar 2024Stable angina pectoris (SAP) is an ischemic heart disease caused by coronary artery stenosis, which usually occurs during physical activity or emotional excitement. For...
BACKGROUND
Stable angina pectoris (SAP) is an ischemic heart disease caused by coronary artery stenosis, which usually occurs during physical activity or emotional excitement. For this type of angina pectoris, reducing the oxygen demand of the heart and increasing the coronary blood flow are the key goals of treatment.
OBJECTIVE
To analyze nicorandil's application effect and adverse reactions in patients with SAP.
METHODS
Sixty patients with stable angina pectoris admitted to our hospital from December 2020 to May 2022 were randomly selected and included in this study. They were divided into nicorandil group (n=30) and conventional group (n=30). The clinical efficacy, duration of chest pain, number of heart attacks per week, cardiac function indexes, improvement of exercise tolerance, occurrence of adverse reactions, and Seattle Angina Scale (SAQ) score were observed.
RESULTS
The effective rate of nicorandil group was 93.33%, which was much higher than that of conventional group (73.33%, P < .05). The results showed that the nicorandil group was significantly better than the conventional group in clinical efficacy, duration of chest pain, number of attacks per week, cardiac function index, improvement of exercise tolerance, occurrence of adverse reactions and SAQ score (P < .05).
CONCLUSIONS
Nicorandil can improve the clinical symptoms of SAP patients, significantly reduce the duration and frequency of chest pain attacks, and enhance cardiac function indicators. It can be used as an effective drug choice to reduce the frequency and intensity of angina pectoris attacks and is worthy of wide clinical application.
PubMed: 38430173
DOI: No ID Found