Use Of Nicorandil Research Articles

Assessment of cardiac parameters after the administration of nicorandil before primary percutaneous coronary intervention.

To assess cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes and major adverse cardiac events after treatment with nicorandil before primary percutaneous coronary intervention. The comparative, analytical study was conducted from October to November 2022 at the Pharmacology Department of Army Medical College, National University of Medical Sciences, Rawalpindi, Pakistan, in collaboration with the Rawalpindi Institute of Cardiology, Rawalpindi. The sample comprised ST-elevated myocardial infarction patients of either gender aged at least 30 years with an ejection fraction of at least 35% undergoing primary percutaneous coronary intervention. Participants were selected based on the above-mentioned inclusion and informed consent was taken before their enrolment in this research study. The sample was randomised into control group A receiving conventional acute coronary syndrome treatment, and intervention group B receiving nicorandil in addition to the conventional treatment. Cardiac troponin I and creatine kinase-myocardial band levels, electrocardiogram changes, and major adverse cardiac events noted and compared. Data was analysed using SPSS 26. Of the 140 patients, 70(50%) were in each of the 2 groups. In group B, 60(85.7%) patients achieved a completely settled ST segment on electrocardiogram compared to 25(35.7%) in group A (p=0.001). There was a significant inter-group difference with respect to cardiac troponin I value 6 hours after percutaneous coronary intervention and major adverse cardiac events (p<0.05), but creatine kinase-myocardial band level was no significantly different between the groups (p=0.761). Prophylactic use of nicorandil in ST-elevated myocardial infarction patients decreased the incidence of reperfusion injury.

Perioperative myocardial injury in patients with coronary artery disease during elective lower limb surgery

Aim. To assess the prevalence of ischemic myocardial injury and the cardioprotective effect of nicorandil by assessing high-sensitivity cardiac troponin (hs-cTn) in patients with stable coronary artery disease (CAD) during elective lower limb surgery, as well as to identify predictors of adverse cardiac events.Material and methods. The study included 70 patients with stable coronary artery disease hospitalized for elective autogenous femoropopliteal bypass (FPB) surgery. After randomization, all patients were divided into two following groups: control group — 35 patients; main group — 35 patients, who, in addition to standard therapy, were prescribed nicorandil (Cordinic, PIQ-PHARMA) in a single dose of 20 mg 2 hours before surgery. In the postoperative period, the incidence of myocardial injury was assessed by hs-cTn increase. The obtained primary data were subjected to mathematical processing using the R-Studio software package (R language).Results. At baseline, patients in both groups were comparable in clinical characteristics, therapy, and duration of vascular surgery. In the main group of patients receiving nicorandil, a significant decrease in the incidence of perioperative myocardial injury was noted. In 5 patients of the control group, hs-cTn level 24 hours after surgery exceeded the threshold value, which indicated myocardial injury in the early postoperative period. In the nicorandil group, there was no hs-cTn increase (14% vs 0%, p=0,027). Regression analysis identified a predictor of perioperative myocardial injury — left ventricular ejection fraction (LVEF) &lt;50%. LVEF &lt;50% increases the risk of myocardial injury in the early postoperative period by 7,36 times (p=0,04) and 9,15 times (p=0,048) according to univariate and multivariate regression analysis, respectively.Conclusion. Perioperative myocardial injury is a common complication in patients with CAD undergoing lower extremity revascularization. The use of nicorandil (Cordinic, PIQ-PHARMA) before elective revascularization surgery helps reduce the incidence of ischemic myocardial injury in the early postoperative period and is not accompanied by adverse reactions, which rationales this approach to improve the clinical outcomes of lower extremity revascularization in patients with stable CAD. A predictor of myocardial injury, determined by hs-cTn, is a LVEF &lt;50%.

Cardioprotective and anti-anginal efficacy of Nicorandil: A Comprehensive Review.

Angina pectoris remains a significant burden despite advances in medical therapy and coronary revascularization. Many patients (up to 30%) with angina have normal coronary arteries, with coronary microvascular disease (CMD) and/or coronary artery vasospasm (CAVS) being major drivers of the myocardial demand-supply mismatch. Even among patients revascularized for symptomatic epicardial coronary stenosis, recurrent angina remains highly prevalent. Medical therapy for angina currently centers around two disparate goals, viz secondary prevention of hard clinical outcomes and symptom control. Vasodilators such as nitrates have been first-line anti-anginal agents for decades, along with beta-blockers and calcium channel blockers. However, efficacy in terms of symptoms control is heterogenous, depending on underlying mechanism(s) of angina in an individual patient, often necessitating multiple agents. Nicorandil (NCO) is an anti-anginal first discovered in the late 1970s with a uniquely dual mechanism of action. Like a typical nitrate, it mediates medium-large vessel vasodilation via nitric oxide. Additionally, NCO has ATP-dependent potassium channel-agonist activity (KATP), mediating microvascular dilatation. Hence, it has proven effective in both CAVS and CMD, typically challenging patient populations. Moreover, emerging evidence suggests cardiomyocyte protection against ischemia via ischemic preconditioning (IPC) may be mediated via KATP-agonism. Finally, there is now fairly firm evidence in favor of NCO in terms of hard event reduction among patients with stable coronary artery disease (CAD), following myocardial infarction, and perhaps even among patients with congestive heart failure (CHF). This review aims to summarize the mechanism of action of NCO, its efficacy as an anti-anginal, and current evidence behind its impact on hard outcomes. Finally, we review other cardiac and emerging non-cardiac indications for NCO use.Keywords: angina, stable ischemic heart disease, anti-anginal, efficacy, cardioprotective.

Real-World Major Adverse Cardiovascular Events of Nicorandil and Nitrate in Coronary Heart Disease in Central China: A Retrospective Cohort Study

Objective: Residual cardiovascular risk in patients with coronary heart disease (CHD) still needs to be addressed in real-world practice. This study aimed to examine the clinical effectiveness of nicorandil and nitrate in addition to optimal treatment for CHD patients. Methods: This retrospective cohort study included patients with CHD between October 2009 and March 2020 from 2 tertiary hospitals in Wuhan, China. Patients were grouped into nicorandil and nitrate groups depending on the first recorded antianginal therapy. Demographic and clinical data were collected from databases of the 2 hospitals. The primary outcome was cumulative 18-month major adverse cardiovascular event (MACE)-free survival, which was evaluated by Kaplan-Meier analysis. Propensity score matching (PSM) and multivariate Cox regression were adopted to adjust for confounding factors. Results: A total of 14,275 patients were analyzed, including 590 and 13,685 patients in the nicorandil and nitrate groups, respectively. With a median follow-up of 0.88 (Q1, Q3: 0.21, 1.54) years, the cumulative 18-month MACE-free survival rates were comparable between the 2 groups (80.0% vs. 75.0%, adjusted hazard ratio (aHR): 1.04, 95% confidence interval (CI): 0.42–2.56, P = 0.982,7) after 1:4 PSM. The cumulative 18-month stroke-free survival rate was significantly higher in the nicorandil group compared to the nitrate group (93.0% vs. 84.0%, aHR: 0.56, 95% CI: 0.34–0.92, P = 0.023,5). Conclusion: This retrospective study showed that nicorandil and nitrate have similar 18-month rates of MACEs in CHD patients, but nicorandil is associated with lower incidence of stroke compared to nitrate. More studies need to be conducted to validate this association and explore the long-term benefit of nicorandil use on the occurrence of MACEs in the future.

Cardio protective effect of nicorandil in reperfusion injury among patients undergoing primary percutaneous coronary intervention.

To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role.

Use of nicorandil is associated with increased risk of incident atrial fibrillation.

Background: Nicorandil will activate ATP-sensitive potassium channel (KATP). However, activation of potassium channels plays an important role in the mechanism of atrial fibrillation (AF) or atrial flutter (AFL). Whether use of nicorandil might contribute to initiation and/or perpetuation of AF/AFL remained unknown. We determined the relationship between use of nicorandil and risk of atrial fibrillation and determined its molecular mechanism.Methods: We performed a nested case-control study using a cohort from the National Health Insurance Research Database (NHIRD) of Taiwan. The association between nicorandil use and risk of atrial fibrillation/flutter was estimated by logistic regression model. We also performed molecular, cellular and animal studies to explain the association.Results: A total of 715 individuals who experienced AF/atrial flutter were matched to 72,215 controls. New use of nicorandil was found to be associated with increased risk for AF/AFL (odds ratio [OR], 2.34; 95% CI 1.07–5.13) compared to nitrate use. We found the expression of KATP subunits Kir6.2 and SUR2A in human and rat left atrial tissues. Furthermore, nicorandil directly shortened action potential duration (APD) in rat left atrium and shortened the QT interval of cultured human induced pluripotent stem cell (iPSC) derived cardiomyocytes (iPSC-CMs).Conclusions: Use of nicorandil was found to be associated with increased risk of AF/AFL. We also showed the expression of KATP subunits in human atria, and a possible mechanism that use of nicorandil increases the risk of AF through activation of KATP and shortening of atrial APD.

Comparison of the outcomes of the prolonged antianginal therapy use in stable coronary artery disease patients according to the data of randomized and observational studies

ObjectiveTo compare the results of treatment with antianginal drug nicorandil in patients with stable coronary artery disease according to the results of the observational study (OS) «NIKEA» and randomized controlled trial (RCT) «IONA». Methods«NIKEA » observational program included 590 patients with stable angina pectoris. Subgroups in the OS were formed based on the adherence to nicorandil use. Adherence was assessed during follow-up direct questioning. «IONA » RCT included 5126 patients with stable angina pectoris. ResultsFollow-up period and mean age of patients were equal in OS and RCT. In OS the group of adherent to nicorandil use patients had fewer males, life-saving drugs were administered significantly more often than in RCT, comorbidities (arterial hypertension, peripheral atherosclerosis and diabetes mellitus) were more pronounced. Angina pectoris class III was diagnosed in 32% of the OS patients vs 11% of the RCT patients, and class I – in 4.4% and 26%, respectively (р<0.001). Both in RCT and OS, there were significantly fewer cases of all cardiovascular events in the groups of nicorandil and adherent to nicorandil use patients in comparison with the groups of placebo and nonadherent patients. Both in RCT and OS the use of nicorandil led to significant decrease in the risk of all cardiovascular events. ConclusionResults of the efficacy and effectiveness studies complement each other and give the opportunity to assess the realisation of the RCT results in real clinical practice.

Abstract 12633: Use of Nicorandil is Associated With Increased Risk of Incident Atrial Fibrillation- A Population-based Nested Case-control Study and Molecular Studies to Explain the Association

Background: Nicorandil is a potent vasodilator of coronary vessels through its effect on opening of ATP-sensitive potassium channel (KATP), and has been used as an antianginal agent. Activation of potassium channels play an important role in the mechanism of atrial fibrillation (AF) or atrial flutter (AFL). Accordingly, whether use of nicorandil might contribute to initiation and/or perpetuation of AF/AFL remained unknown. Objectives: To determine the relationship between use of nicorandil and risk of atrial fibrillation. Methods: We performed a nested case-control study using a cohort of 1 million people assembled from the National Health Insurance Research Database (NHIRD) of Taiwan. The association between nicorandil use and risk of atrial fibrillation was estimated by logistic regression model. We also performed molecular and cellular studies to explain the association. Results: A total of 715 individuals who experienced atrial fibrillation or atrial flutter were matched to 72,215 controls. To account for the potential unmeasured confounders, we identified nitrate users in the same cohort as an active comparator. After adjustment, new use of nicorandil was found to be associated with increased risk for atrial fibrillation or atrial flutter (odds ratio [OR], 2.34; 95% CI 1.07-5.13) compared to nitrate use. Activation of potassium channel shortens atrial action potential duration (APD), which subsequently perpetuates AF. Dysfunction of mutated sarcKATP channels in atrial cells may lead to electrical instability and atrial fibrillation. We found expression of KATP in human atrial tissues. Furthermore, nicorandil directly shortened APD and the QT interval of cultured induced pluripotent stem cell (iPSC) derived cardiomyocytes (iPSC-CMs). Conclusion: Use of nicorandil, especially new use, was found to be associated with increased risk of AF or AFL. We also first showed the expression of KATP in human atria and use of nicorandil may promote or increase the risk of AF through activation of KATP and shortening of atrial APD.

The Efficacy and Safety of Nicorandil for Periprocedural Myocardial Injury in Patients Undergoing PCI: A Meta-Analysis

Purpose To evaluate the efficacy and safety of nicorandil for periprocedural myocardial injury in patients undergoing PCI through meta-analysis of randomized controlled trials. Methods We analyzed the clinical data of patients including the incidence of periprocedural myocardial injury (PMI) and major adverse cardiovascular events (MACE) from selected articles. RCTs were retrieved from medical literature databases. RR and 95% confidence intervals (CI) were calculated to compare the endpoints. Results In total, 15 articles (16 trial comparisons) were retrieved which contained 2221 patients. In general, 1130 patients (50.9%) were randomized to the experimental group, whereas 1091 patients (49.1%) were randomized to the control group. The result showed that nicorandil significantly reduced the incidence of PMI and MACE after PCI compared to the control group. Conclusions Overall, early use of nicorandil in patients undergoing percutaneous coronary intervention (PCI) was associated with a significant reduction of PMI and MACE.

Diagnostic utility and safety of intracoronary nicorandil as a hyperemic agent for the measurement of fractional flow reserve

We investigated the diagnostic utility and safety of intracoronary bolus administration of nicorandil compared with intravenous administration of adenosine for evaluating FFR in patients with intermediate (40–70%) coronary stenosis. The FFR values obtained with nicorandil and adenosine showed linear relationship. This correlation is statistically significant with regression coefficient of 0.932 (R2 = 0.834, p < 0.001). The side effects such as bronchospasm, hypotension, and bradycardia were significantly higher after administration of adenosine compared to nicorandil (20% vs. 1.66%, p = 0.001). Intracoronary use of nicorandil seems to be promising in offering the advantages of lesser side effects, similar efficacy, and lesser cost as compared to adenosine.

Efficacy, Safety and Long-term Outcomes of Nicorandil Use in Patients with Stable Ischemic Heart Disease According to the Results of Randomized and Observational Studies

Working Group of the NIKEA Study. Yekaterinburg: Akulina E.N., Reznik I.I.; Izhevsk: Grebnev S.A., Yezhov A., Shinkareva S.E.; Krasnodar: Kudryashov E.A., Skibitsky A.V., Skibitsky V.V., Fendrikova A.V.; Krasnoyarsk: Altayev V.D., Matyushin G.V., Nemik D.B., Pitaev R.R., Samokhvalov E.V., Stolbikov Yu.Yu.; Moscow: Balashov I.S., Voronina V.P., Gaisenok O.V., Dmitrieva N.A., Zagrebelny A.V., Zakharova A.V., Zelenova T.I., Kolganova E.V., Leonov A.S., Lerman O.V., Maximova M.A., Sladkova T.A., Shestakova G.N.; Novosibirsk: Kuimov A.D., Shurkevich A.A.; Omsk: Goodilin V.A., Loginova E.N., Nechaeva G.I.; Orel: Zhuravleva L.L., Lobanova G.N., Luneva M.M., Mitroshina T.N.; Orenburg: Kondratenko V.Yu., Libis R.A.; Rostov-on-Don: Dubishcheva N.F., Kalacheva N.M., Kolomatskaya O.E., Romadina G., Skarzhinskaya N.S., Chesnikova A.I., Chugunova I.B.; Ryazan: Dobrynina N.V., Nikolaev A.S., Trofimova Ya.M., Yakushin S.S.; Tula: Berberfish L.D., Gomova T.A., Gorina G.I., Dabizha V.G., Zubareva L.A., Nadezhkina K.N., Nikitina V.F., Renko I.E., Soin I.A., Yunusova K.N.Background. Nicorandil is an antianginal drug for which, the ability to positively influence the prognosis of patients (pts) with stable ischemic heart disease (IHD) was confirmed in a randomized controlled trial (RCT) of IONA (the Impact Of Nicorandil in Angina). To study whether the results of RCTs are reproduced in real clinical practice seems to be an actual scientific and practical task.Aim. To compare the data on the effectiveness and safety of nicorandil in pts with stable IHD obtained in the NIKEA observational study (OS) and in the IONA randomized study.Material and methods. 590 pts with IHD and stable angina pectoris were included in the OS NIKEA. All pts were recommended to take nicorandil in addition to the standard antiischemic therapy. 21 months after being included in the study, 524 pts received a phone call. During the telephone contact with pts or their relatives, the life status of pts was determined. According to these results of the survey data were obtained, that 15 people died and 509 pts were alive. The events included in the primary combined endpoint (PCEP) were also determined: death from all causes, new cases of acute myocardial infarction and acute cerebrovascular accident, unscheduled operations of myocardial revascularization, hospitalization for decompensation of chronic heart failure, atrial fibrillation, unstable angina, information on taking nicorandil and other drug therapy, adverse events of drug treatment have been reported. A comparative analysis of the results of the OS NIKEA and RCT IONA was carried out. The results of the IONA study were taken according to the publication in the Lancet 2002. A comparative analysis of the results of the effectiveness of nicorandil in real practice (according to the OS results) was performed with the data obtained in the RCT: the nicorandil/placebo groups in the RCT were compared with the adherent/non-adherent nicorandil groups in the OS.Results. The follow-up duration in both studies was similar and averaged 1.6±0.5 years at RCT IONA and 1.8±0.4 years at NIKEA study. The average age of pts was 67,0±8,0 years in RCT and 65.1±9.6 years in OS. In pts of OS more pronounced comorbidity was noted (cardiovascular diseases, diabetes mellitus). Drugs that favorably affect the prognosis in pts with IHD were more often prescribed to NIKEA study pts (p&lt;0.05). In both RCTs and OS, the antianginal effectiveness of nicorandil was confirmed. According to the OS results, a reduction in the number of angina attacks and a decrease in the need for short-acting nitrates were demonstrated. The frequency of PCEP components was higher in RCT.Conclusion. Long-term outcomes according to the NIKEA observational program for various components of the PCEP turned out to be similar to the results of RCT IONA. It is demonstrated the efficacy of nicorandil in real clinical practice.

PCV145 ASSOCIATION BETWEEN NICORANDIL AND GASTROINTESTINAL ULCERS: A POPULATION-BASED STUDY

The association between nicorandil (NCR) use, an antianginal drug, and the risk of gastrointestinal (GI) ulcers was evaluated in angina patients using Korean healthcare big data. A cross-sectional study was conducted using 2014 HIRA-NPS data including patients aged 40 years or more. A 3-month washout period was placed to identify new drug users and incident safety outcomes. A new NCR user was captured from a 3-month follow-up period followed by a 6-month period for detecting the safety outcome of GI ulcer. The association between NCR use and GI ulcers was evaluated using multivariate logistic regression analysis. The study population included 1,767 nicorandil users representing 58,900 Korean patients. Of the nicorandil users, 4,667 (8%) patients were reported to have one or more of GI ulcers as an adverse drug reactions (ADR). As compared to other anti-anginal medications including molsidomine, trimetazidine, nitrates, and calcium channel blockers, NCR was not found to increase the risk of GI ulcer (adjusted odds ratio [aOR] 1.119; 95% CI: 0.607 – 2.064) after adjusting confounders including age, sex, insurance type, and clinical comorbidities of diabetes, inflammatory bowel diseases, and any types of cancer. Among concurrent medications including corticosteroids, bisphosphonates, aspirin, anti-platelet agents, selective serotonin reuptake inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs), only corticosteroids (aOR 1.615; 95% CI: 1.124 – 2.319) and NSAIDs (aOR 1.776; 95% CI: 1.125 – 2.803) significantly increased the risk of GI ulcers. Using a 1-year real-world data available from the Korean healthcare insurance system, NCR did not significantly increase the risk of GI ulcers as compared to other anti-anginal medications. As the study only allowed a 6-month follow-up and the standard regimen did not exceed 15mg per day, which was lower than the ADR reported dosage of 60mg or higher, further research including longitudinal follow-ups and other real-world data are needed.

The effect of continuous nitrate intake on the disease prognosis in patients with vasospastic angina pectoris according to prolonged outpatient monitoring

Aim . Although nitrates are widely used as a concomitant therapy with calcium channel blockers (CCBs) for vasospastic angina (VSA), their prognostic contribution remains unclear. The present study aimed to examine the prognostic impact of chronic nitrate therapy in patients with VSA. Material and methods . 129 patients with VSA, registrated in clinical diagnostic center, were enrolled in the study (median 66 years, male/ female, 90/39). The primary endpoint was defined as major adverse cardiac events (MACE). The propensity score matching and multivariable Cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. Among the patients, 65 people (49%) were treated with nitrates, including conventional nitrates (for example, nitroglycerin, isosorbide mono- and dinitrate). 36 people received nicorandil. CCBs were used in >90% of patients. Results . During the median follow-up period — 19 months — 21 patients (19%) reached the primary endpoint. Conformity analysis by screening showed that the total incidence of MACE is comparable between patients with and without nitrates (11 vs. 8% at 1 year; risk ratio (RR): 1,28; 95% confidence interval (CI): 0,72-2,28, P=0,40). Although nicorandil has a neutral prognostic effect on VSA (RR: 0,80, 95% CI: 0,28-2,27, P=0,67), the Cox multivariate model has identified potential harm from co-use of conventional nitrates and nicorandil (RR: 2,14, 95% CI: 1,02-4,47, P=0,044), especially with simultaneous treatment with nitroglycerin and nicorandil. Conclusion . Permanent nitrate therapy in combination with CCBs did not improve long-term prognosis in patients with VSA. The additional use of nicorandil has a neutral prognostic effect.

Bevacizumab Versus Anti-preeclamptic Drugs: Evaluation With Three-dimensionally Co-cultured Human Mini Tumors.

Both bevacizumab (BEV) and soluble fms-like tyrosine kinase-1 (sFlt-1) have demonstrated anti-angiogenic effects, thereby causing hypertension and proteinuria. We hypothesized that anti-preeclamptic drugs that combat the action of sFlt-1 may reduce BEV's anti-tumor efficacy. 3D co-cultured human mini-tumors consisting of endothelial cells, fibroblasts, and cancer cells were developed. The influence of anti-preeclamptic drugs and BEV on the invasion of mini-tumors embedded in collagen gel was evaluated. Mini-tumor spheroids that contained MDA-MB-231 cells showed higher invasion ability than spheroids with A549. Among the six anti-preeclamptic drugs investigated, only nicorandil enhanced the invasion of mini-tumors and inhibited the action of BEV. Glibenclamide, an ATP-sensitive potassium channel inhibitor, completely quenched the action of nicorandil on mini-tumors. In the human mini-tumor model, nicorandil aggravated the invasion of mini-tumors. These data raise the possibility that concomitant use of nicorandil counteracts the efficacy of BEV therapy.

Effect of sequential nicorandil on myocardial microcirculation and short-term prognosis in acute myocardial infarction patients undergoing coronary intervention

This study aims to observe the effects of the intracoronary and peripheral venous administration of nicorandil for the postoperative myocardial microcirculation and short-term prognosis of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) treatment. A total of 140 STEMI patients were divided into three groups according to different patterns of administration: sequential nicorandil group, intracoronary nicorandil group and control group. The main observation indexes included coronary blood flow and myocardial perfusion immediately after PPCI, while the secondary observation indexes included major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF) during the period of hospitalization. After PPCI, the difference in the proportion of patients with thrombolysis in myocardial infarction (TIMI) flow grade 3 among the three groups was statistically significant (P=0.036), where this proportion was higher in the sequential nicorandil group and intracoronary nicorandil group than in the control group (P=0.022 and P=0.047); The difference in corrected TIMI frame count (CTFC) among the three groups was statistically significant (P=0.022), where CTFC was lower in the sequential nicorandil group and intracoronary nicorandil group than in the control group (P=0.010, P=0.031); The differences in the proportion of patients with complete ST resolution (STR) and advancing of enzyme peak time to within 12 h between each two groups were statistically significant (P<0.001), where this proportion was the highest in the sequential nicorandil group; The difference in the CK-MB peak among the three groups was statistically significant (P=0.036), where the CK-MB peak was lower in the sequential nicorandil group than in the control group (P=0.012); The difference in the incidence of MACE between each two groups was statistically significant (P<0.001), where this incidence was the lowest in the sequential nicorandil group; The differences in the proportion of patients with advancing of enzyme peak time to within 14 h and LVEF among the three groups were not statistically significant (P=0.722 and P=0.284). Compared with intracoronary use alone, the intracoronary and peripheral intravenous use of nicorandil can better improve myocardial microcirculation and short-term prognosis.

Effect of nicorandil, on blood glucose level in alloxan induced diabetic rats and its pharmacodynamic interaction with glibenclamide

Background: Diabetes increases the risk of macrovascular complications and is often associated with angina in patient. Currently nicorandil, a potassium channel opener is being frequently used for the prevention and long-term treatment of angina pectoris. Glibenclamide exerts its antidiabetic action by closing the ATP sensitive potassium channels. Simultaneous use of nicorandil may antagonizes this action and may worsens the existing diabetes. To evaluate the pharmacodynamic interaction present study has been taken to study the effect of Nicorandil, a potassium channel opener on blood glucose level of alloxan induced diabetic rats and its pharmacodynamics interaction with Glibenclamide.Methods: Albino rats, weighing 150-200gm of male sex were used for the study. Diabetes was induced by injecting alloxan monohydrate 2% solution intra peritoneally in a dose of 150mg/kg body weight. Animal with Fasting Blood Sugar level between 250-300g/dl was selected for study and they were divided into 4 groups of 5 animals each. Group I- serving as control received 0.5ml normal saline orally for 28 days. Group II was given glibenclamide (0.5mg/kg body wt) for 28 days. Group III was treated orally with nicorandil (0.3mg/kg body wt) for 28 days. Group IV was given glibenclamide (0.5mg/kg) and nicorandil (0.3mg/kg) for 28 days. Fasting Blood Sugar level was recorded in all rats on 1st,3rd,7th,14th,21st and 28th day of the treatments.Results: results showed that glibenclamide significantly reduce blood sugar level (p &lt;0.05) Wherase nicorandil showed rise in blood glucose level (p &lt;0.05) While the combination (glibenclamide + nicorandil) showed rise in blood glucose (p &lt;0.05) overall.Conclusions: Nicorandil worsen the existing diabetes and to be avoided or replaced with alternative drug in case of diabetes being treated with sulfonyl urease group of drugs.

Nicorandil-induced ulcerations: a 10-year observational study of all cases spontaneously reported to the French pharmacovigilance network.

Nicorandil-induced ulcers remain often poorly recognised, with a late diagnosis and an inadequate management. We aimed to provide a clinical overview of the 148 spontaneously reported cases of nicorandil-induced ulcers to the French pharmacovigilance network between 2005 and 2014 and to complete this picture with worldwide published cases over the same period. Spontaneously reported nicorandil-induced ulcers were mainly mucosal (oral and anal) with a previous trauma in 23·0% of patients, revealed by a severe complication in 12·8% of cases. The mean cumulative dose of nicorandil was higher in serious cases. The median delay between the start of nicorandil use and the onset of the ulcer was 23·4 months, and after the ulcer was diagnosed, the median time to incriminate nicorandil was still 3·3 months, being shorter for mucosal ulcerations than for cutaneous ulcerations (5·2 versus 14·0 months, P = 0·001). The anatomic distribution in the 199 published cases differed slightly, but delays were similar. The hypothesis of mechanism becomes more precise, leaving no doubt about the necessity to discontinue the treatment. Practitioners need to be aware that nicorandil-induced ulcers can occur in many locations, possibly multiple and complicated, and should be simply managed by discontinuing treatment with no further reintroduction of nicorandil.

Correction of morphofunctional disturbances arising when modelling Preeclampsia with resveratrol and nicorandil

Introduction: Preeclampsia is one of the most serious diseases of the second half of pregnancy and is surely amongst the top three causes of maternal mortality. Therefore, the creation of new drugs for preventing and correcting preeclampsia is an urgent task.&#x0D; Methods: In the experiment, an ADMA-like L-NAME-induced model of preeclampsia was reproduced. To assess the emerging morphofunctional disorders, the following parameters were used: blood pressure, endothelial dysfunction coefficient, microcirculation in the placenta, proteinuria, fluid content in the large omentum, concentration of terminal metabolites in the blood plasma, morphological state of the placenta and kidneys and morphometric parameters of the foetus.&#x0D; Results and Discussion: Injection of L-NAME into the animals from the 14th to the 20th day of pregnancy causes disorders: an increase in systolic and diastolic blood pressure by 1.4 and 1.5 times, an increase in proteinuria by 3.3 times and an increase in the fluid content in a large omentum from 45.82 ± 1.82% to 54.73 ± 1.96%, which correspond to disorders due to preeclampsia in pregnant women. There was also a disturbance of endothelial function, as evidenced by an increase in the coefficient of endothelial dysfunction (CED) by 2.9 times. The use of resveratrol leads to a pronounced correction in the changes that occur: a decrease in systolic and diastolic arterial pressure by 1.2 and 1.3 times, a decrease in proteinuria by a factor of 1.9 and a decrease in the fluid content in the large omentum to 50.00 ± 1.25%. The use of nicorandil leads to a pronounced correction in the resulting changes: a decrease in the diastolic blood pressure by 1.14 times, a decrease in proteinuria by a factor of 1.7 and a decrease in the fluid content in the large omentum to 50.57 ± 2.08%. CED decreased 1.7 times. When combining their use with amlodipine, the positive effects increased: systolic and diastolic blood pressure decreased 1.13 and 1.24 times and 1.14 and 1.23 times, respectively, proteinuria decreased 2.7 and 2.3 times, the fluid content in the large omentum was reduced to 44.54 ± 1.80% and 46.73 ± 1.30%. CED decreased 1.7 and 2.3 times. The administration of glibenclamide together with resveratrol and nicorandil removes a significant part of their positive effects.&#x0D; Conclusion: Resveratrol and nicorandil have a significant positive effect in the correction of morphofunctional disorders in animals with ADMA-like preeclampsia. Activation of K+ATP channels plays a significant role in the realisation of their positive effects.

Nicorandil and cutaneous ulcerations, their misdiagnosis and consequences: Illustration by five cases reports and a review of the French pharmacovigilance database

While physicians increasingly recognize nicorandil-related mucocutaneous ulcerations, there are still misdiagnoses, particularly in the case of unusual location and late onset ulceration after nicorandil introduction. The goal of our study was to remind clinicians about the link between nicorandil use and the development of cutaneous ulcerations and to highlight the risk of misdiagnosis. We describe five reports diagnosed by the same dermatologist, complemented by an analysis of the French pharmacovigilance database (FPVD) from 1 January 1994 to 5 January 2017. During this period, 28 reports of strict cutaneous ulcerations due to nicorandil, in addition to our five reports, were registered in the FPVD. For those 28 reports, the time to onset between nicorandil introduction and cutaneous ulcerations was quite long and exceeded one year in 16 reports (information specified in 25 reports). The delay between ulcerations observation and nicorandil discontinuation was variable, with immediate diagnosis in seven reports, but ranged from fifteen days to twelve years in 21 reports. The main locations were lower limbs, thorax and face. Ulcerations could be localized on surgery or trauma scars. Regression after nicorandil discontinuation was observed in all but two reports and ranged from three days to three months. Characteristics were comparable in our five patient's series. All patients exposed to nicorandil and healthcare practitioners prescribing nicorandil should be aware of the risk of cutaneous ulcerations to enable early diagnosis and drug withdrawal. The risk of misdiagnosis of this serious adverse drug reaction, along with the risk of sequelae, the costs of unnecessary additional investigations and the recent update on nicorandil as second-line treatment for stable angina, with existing alternative drugs, question about the benefit/risk balance of nicorandil.

Effect of nicorandil on ventricular arrhythmia in patients with acute ST-segment elevation myocardial infarction underwent emergent percutaneous coronary intervention treatment

Objective: To investigate the effect of nicorandil on ventricular arrhythmia in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with emergent percutaneous coronary intervention (PCI). Methods: A total of 120 acute STEMI patients treated with emergent PCI in our hospital from January 2015 to June 2016 were randomly divided into control group and experiment group (n=60 each). Patients in both groups received conventional therapy.Patients in experiment group took 10 mg nicorandil orally before PCI and received oral nicorandil treatment (15 mg/d, three times daily) for 3 days.QT disperse(QTd), correct QTd(QTcd) and the occurrence rate of ventricular arrhythmia were compared between two groups. Results: QTd at 6, 24, 48 and 72 hours((70.6±4.4), (67.2±5.3), (55.7±8.5), (48.2±8.2) ms, respectively) after PCI was significantly lower in the experiment group than those of control group ((77.1±7.1), (71.3±6.5), (65.1±8.1), (57.2±5.4) ms, all P<0.05). The level of QTd was also significantly lower in the experiment group at 6, 24, 48 and 72 hours((77.5±7.7), (67.7±8.6), (61.2±7.5), (52.9±8.4) ms, respectively) after PCI comared to those of control group ((88.6±8.1), (79.2±7.8), (74.4±7.4), (69.6±8.6) ms, all P<0.05). There was no significant difference in the incidence of reperfusion arrhythmia during PCI procedure between the two groups.The prevalence of the ventricular premature beat in the experiment group (25/60, 41.7%) was significantly lower than in the control group(45/60, 75.0%) within 3 days after PCI(P<0.01), the prevalence of the no sustained ventricular tachycardia and ventricular fibrillation in the experiment group(6/60, 10.0%) was also significantly lower than in the control group (18/60, 30.0%, P<0.01) within 3 days after PCI. Conclusions: Nicorandil use prior and post PCI could decrease the occurrence rate of ventricular arrhythmia in STEMI patients undergoing emergent PCI, and this effect might be related with reduced QTd and QTcd post medication.