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Efficacy of nicorandil on the prevention of contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention.
Zhang, X, Yang, S, Zhang, P, Fu, N
Coronary artery disease. 2020;(3):284-288
Abstract
OBJECTIVES The purpose of this study was to explore the effect of nicorandil on the incidence of contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention. METHODS This study randomized 300 patients undergoing percutaneous coronary intervention to receive conventional treatment in the control group (hydration only; n = 150) vs. nicorandil therapy (nicorandil 10 mg three times daily plus hydration; n = 150). The primary endpoint was the incidence of contrast-induced nephropathy, defined as rise in serum creatinine ≥44.2 μmol/L or >25% above baseline within 72 hours after exposure to contrast administered during percutaneous coronary intervention. Secondary endpoints included differences in post-percutaneous coronary intervention serum creatinine, blood urea nitrogen, creatinine clearance rate, cystatin-C, and occurrence of major adverse events. RESULTS Contrast-induced nephropathy incidence was 3.3% (5/150) in the nicorandil group vs. 10.7% (16/150) in the control group (P < 0.05). At 48 and 72 hours after contrast administration, cystatin-C levels were significantly lower and creatinine clearance rate were significantly higher with nicroandil therapy compared to conventional treatment (all P values <0.05). No statistical difference was observed in the incidence of major post-procedure side effect events in hospital and fourteen days of follow-up period between the nicorandil group and control group (3.3% vs. 4.0%, P > 0.05). CONCLUSION Compared to conventional treatment, oral nicorandil therapy was associated with less contrast-induced nephropathy and improved renal function following contrast administration during percutaneous coronary intervention.
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The effect of nicorandil in patients with cardiac syndrome X: A meta-analysis of randomized controlled trials.
Jia, Q, Shi, S, Yuan, G, Shi, J, Shi, S, Wei, Y, Hu, Y
Medicine. 2020;(37):e22167
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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.
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Effect of Calcium-Channel Blockade on the Cold-Induced Vasodilation Response.
Milliner, BHA, Brant-Zawadzki, G, McIntosh, SE
Wilderness & environmental medicine. 2020;(3):312-316
Abstract
INTRODUCTION Cold-induced vasodilation (CIVD) is seen in the extremities during exposure to cold. A strong vasodilation response has been associated with a decreased risk of cold injury. Increasing CIVD might further decrease this risk. The calcium-channel blocker nifedipine causes vasodilation and is used to treat Raynaud's syndrome and chilblains. Nifedipine is also used for high altitude pulmonary edema and could potentially serve a dual purpose in preventing frostbite. The effects of nifedipine on CIVD have not been studied. METHODS A double-blind crossover study comparing nifedipine (30 mg SR (sustained release) orally twice daily) to placebo was designed using 2 sessions of 4 finger immersion in 5°C water, with 24 h of medication pretreatment before each session. Finger temperatures were measured via nailbed thermocouples. The primary outcome was mean finger temperature; secondary outcomes were mean apex and nadir temperatures, first apex and nadir temperatures, subjective pain ranking, and time of vasodilation onset (all presented as mean±SD). RESULTS Twelve volunteers (age 29±3 [24-34] y) completed the study. No significant difference in finger temperature (9.2±1.1°C nifedipine vs 9.0±0.7°C placebo, P=0.38) or any secondary outcome was found. Pain levels were similar (2.8±1.6 nifedipine vs 3.0±1.5 placebo, P=0.32). The most common adverse event was headache (32% of nifedipine trials vs 8% placebo). CONCLUSIONS Pretreatment with 30 mg of oral nifedipine twice daily does not affect the CIVD response in healthy individuals under cold stress.
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Efficacy and safety of the injection of the traditional Chinese medicine salviae miltiorrhizae and ligustrazine hydrochloride for the treatment of perioperative period of fracture: A meta-analysis of randomized controlled trials.
Xie, J, Chen, S, Ding, S
Medicine. 2020;(16):e19777
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BACKGROUND The injection of the traditional Chinese patent medicine salviae miltiorrhizae and ligustrazine hydrochloride injection (SMLHI) has been widely used in treatment of various diseases such as angina pectoris or ischemic stroke in China. We aim to evaluate the efficacy and safety of SMLHI for the treatment of perioperative period of fracture. METHODS A systematic literature search was performed in seven medical databases from their inception until February 2019. 16 studies with randomized controlled trials, totaling 1589 patients, were included in this meta-analysis. The included studies were assessed by the cochrane risk of bias and analyzed by Review Manager 5.3 software. RESULTS The meta-analysis showed that SMLHI for the treatment of perioperative period of fracture was significantly better compared with the control group in terms of the total effective rate. The result showed that SMLHI could significantly reduce the risk of deep vein thrombosis and inflammatory cytokines. Furthermore, the result showed that SMLHI could significantly improve the coagulation function indexes such as prothrombin time, plasma fibrinogen and D-Dimer (P < .0001). CONCLUSIONS This meta-analysis demonstrated that SMLHI may be more effective and safe for the treatment of perioperative period of fracture. However, further and higher quality randomized controlled trials are required to prove treatment outcome.
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Use of vasoactive/vasodilating drugs for systemic sclerosis (SSc)-related digital ulcers (DUs) in expert tertiary centres: results from the analysis of the observational real-life DeSScipher study.
Blagojevic, J, Abignano, G, Avouac, J, Cometi, L, Frerix, M, Bellando-Randone, S, Guiducci, S, Bruni, C, Huscher, D, Jaeger, VK, et al
Clinical rheumatology. 2020;(1):27-36
Abstract
INTRODUCTION DeSScipher is the first European multicentre study on management of systemic sclerosis (SSc), and its observational trial 1 (OT1) evaluated the efficacy of different drugs for digital ulcer (DU) prevention and healing. The aim of this study was to assess current use of vasoactive/vasodilating agents for SSc-related DU in the expert centres by analysing the baseline data of the DeSScipher OT1. METHOD Baseline characteristics of patients enrolled in the OT1 and data regarding DU were analysed. RESULTS The most commonly used drugs, in both patients with and without DU, were calcium channel blockers (CCBs) (71.6%), followed by intravenous iloprost (20.8%), endothelin receptor antagonists (ERAs) (20.4%) and phosphodiesterase 5 (PDE-5) inhibitors (16.5%). Of patients, 32.6% with DU and 12.8% without DU received two drugs (p < 0.001), while 11.5% with DU and 1.9% without DU were treated with a combination of three or more agents (p < 0.001). Sixty-five percent of the patients with recurrent DU were treated with bosentan and/or sildenafil. However, 64 out of 277 patients with current DU (23.1%) and 101 (23.6%) patients with recurrent DU were on CCBs alone. CONCLUSIONS Our study shows that CCBs are still the most commonly used agents for DU management in SSc. The proportion of patients on combination therapy was low, even in patients with recurrent DU: almost one out of four patients with current and recurrent DU was on CCBs alone. Prospective analysis is planned to investigate the efficacy of different drugs/drug combinations on DU healing and prevention. Key Points • The analysis of DeSScipher, the first European multicentre study on management of SSc, has shown that the most commonly used vasoactive/vasodilating drugs for DU were CCBs, followed by intravenous Iloprost, ERAs and PDE-5 inhibitors. • More than half of the patients with recurrent DU received bosentan and/or sildenafil. • However, the proportion of patients on combination therapy of more than one vasoactive/vasodilating drug was low and almost one out of four patients with current and recurrent DU was on CCBs alone.
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Hypothesis: The potential therapeutic role of nicorandil in COVID-19.
Ashour, H, Elsayed, MH, Elmorsy, S, Harb, IA
Clinical and experimental pharmacology & physiology. 2020;(11):1791-1797
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At present, there is yet no specific antiviral treatment or immunization against the newly identified human severe acute respiratory syndrome virus (SARS-CoV2) that results in a rapidly progressive pandemic coronavirus disease 2019 (COVID-19). We believe in a crucial need for a clinical strategy to counteract this viral pandemic based on the known pathogenesis throughout the disease course. Evidence suggests that exaggerated patient's inflammatory response and oxidative stress are likely to aggravate the disease pathology. The resulting endothelial dysfunction further induces fibrosis and coagulopathy. These disturbances can generate severe acute respiratory distress syndrome (ARDS) that can progress into respiratory and circulatory failure. Nicorandil is an anti-anginal vasodilator drug acts by increasing nitric oxide bioavailability and opening of the KATP channel. Recently, nicorandil has been recognized to possess multiple protective effects against tissue injury. Here, we address a possible modulatory role of nicorandil against COVID-19 pathogenesis. We hypothesise nicorandil would be an effective form of adjuvant therapy against COVID-19.
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Effect of KATP channel blocker glibenclamide on levcromakalim-induced headache.
Al-Karagholi, MA, Ghanizada, H, Kokoti, L, Paulsen, JS, Hansen, JM, Ashina, M
Cephalalgia : an international journal of headache. 2020;(10):1045-1054
Abstract
INTRODUCTION Administration of ATP-sensitive potassium channel opener levcromakalim triggers headache in healthy volunteers and migraine attacks in migraine patients. Here, we investigated the effect of ATP-sensitive potassium channel blocker glibenclamide on levcromakalim-induced headache in healthy volunteers. METHODS In a randomized, double-blind, placebo-controlled, three-way cross-over study, 15 healthy volunteers aged 18-40 years were randomly allocated to receive glibenclamide and levcromakalim (day 1), glibenclamide and placebo (day 2), and placebo and placebo (day 3) on three different days separated by at least 1 week. The primary endpoints were the difference in incidence of headache and the difference in area under the curve for headache intensity scores (0-12 hours) between the days. RESULTS Fifteen healthy volunteers completed the 3 days of the study. More participants (12/15, 80%) developed headache on the glibenclamide-levcromakalim day compared to the glibenclamide-placebo day (5/15, 33%) (p = 0.01; mean difference 47%; 95% confidence interval 18-75%) and compared to the placebo-placebo day (1/15, 7%) (p = 0.001; mean difference 73%; 95% confidence interval 48-99%). We found no difference in headache incidence between glibenclamide-placebo day and placebo-placebo day (p = 0.12; mean difference 27%; 95% confidence interval 1.3-52%). The area under the curve for headache intensity was significantly larger on the glibenclamide-levcromakalim day compared to the glibenclamide-placebo day (p = 0.003); and compared to the placebo-placebo day (p = 0.001). We found no difference in the area under the curve between the glibenclamide-placebo day compared to the placebo-placebo day (p = 0.07). The median time to onset for headache after levcromakalim infusion with glibenclamide pretreatment was delayed (180 min) compared to levcromakalim without pretreatment (30 min) from a previously published study. CONCLUSION Glibenclamide administration did not cause headache, and glibenclamide pretreatment did not prevent levcromakalim-induced headache. However, glibenclamide delayed the onset of levcromakalim-induced headache. More selective blockers are needed to further elucidate the role of the ATP-sensitive potassium channel in headache initiation.Trial Registration: ClinicalTrials.gov NCT03886922.
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Comparison of the Effects of Milrinone, Sodium Nitroprusside, and Nitroglycerine for Induced Hypotension in Elderly Patients Undergoing Spine Surgery: A Randomized Controlled Trial.
Huh, J, Chung, H, Hwang, W
Clinical spine surgery. 2019;(8):E366-E371
Abstract
BACKGROUND The use of induced hypotension is limited because of concerns about hypoperfusion to major organs in elderly patients. The aim of this study was to compare the effects of milrinone with those of other vasodilating hypotensive agents on induced hypotension in elderly patients undergoing spine surgery. METHODS In total, 60 patients older than 60 years who underwent lumbar fusion surgeries were randomized to groups M (milrinone), S (sodium nitroprusside), and N (nitroglycerine). The study drug was infused after perivertebral muscle retraction until complete interbody fusion occurred. The infusion dose was adjusted to achieve a fall of 30% in systolic blood pressure or mean blood pressure to 60 to 65 mm Hg. Intraoperative blood loss, grade of the surgical field, and urine output were recorded. RESULTS Intraoperative blood loss per fused spine level was 288.5±94.4 mL in group M, 399.8±60.3 mL in group S, and 367.0±122.5 mL in group N (P=0.002). The grade of the surgical field was similar among the 3 groups (P=0.439). Hourly urine output was 1.4±0.5 mL in group M, 0.7±0.3 mL in group S, and 0.9±0.4 mL in group N (P<0.001). CONCLUSIONS The use of milrinone for induced hypotension led to less intraoperative blood loss and higher urine output than the use of sodium nitroprusside or nitroglycerine in elderly patients undergoing spine surgery.
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Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction.
Al-Mohammad, A
ESC heart failure. 2019;(4):878-883
Abstract
Hydralazine and nitrate combination was the first treatment that showed improved survival of patients with heart failure with reduced left ventricular ejection fraction (HFREF) in the Vasodilator Heart Failure Trial (V-HeFT trial) in 1986. This showed a 34% reduction of mortality at 2 years of follow-up in patients with advanced heart failure (New York Heart Association Class IV). The angiotensin-converting enzyme inhibitor (ACEi), beta-blockers, mineralocorticoid receptor antagonists, and most recently sacubitril-valsartan have superseded the combination of hydralazine and nitrates. However, the latter combination does have a place bridging the survival gap of Black patients with HFREF when added to their standard therapy. This was demonstrated in the African-American Heart Failure Trial (A-HeFT trial) in 2004 when the risk reduction in the Black patients was 43% compared with that in the placebo. This combination may have a potential use in patients with contraindications to the use of ACEi, angiotensin receptor blockers, and sacubitril-valsartan. This is suggested by both the European Society of Cardiology (ESC) Guidelines and the guidelines of the National Institute for Health and Care Excellence (NICE). In this perspective, the role of the combination of hydralazine and nitrates in the treatment of HFREF is reviewed through a synopsis of the evidence base consisting of three randomized controlled studies, several further analyses of subgroups within those trials, a systemic review, and two large observational studies of registry cohorts. The place of the combination in the treatment cascades proposed by heart failure guidelines of the ESC and NICE is explored. This perspective is to remind us of their appropriate roles, particularly given the findings of underuse of this combination in people of African ancestry in Europe.
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Effects of Nicorandil Versus Nitroglycerin on Arterial Oxygenation During Two-Lung Ventilation and One-Lung Ventilation in Patients With Risk Factors for Myocardial Ischemia: A Prospective, Randomized, Double-Blind Study.
Murakami, C, Kawano, H, Kinoshita, M, Kondo, A, Inoue, M
Journal of cardiothoracic and vascular anesthesia. 2019;(3):702-709
Abstract
OBJECTIVES To compare the effects of nicorandil and nitroglycerin on arterial oxygenation during two-lung ventilation (TLV) and one-lung ventilation (OLV) in patients with risk factors for myocardial ischemia. DESIGN A prospective, randomized, double-blind study. SETTING A tertiary care hospital. PARTICIPANTS Fifty-six patients scheduled for elective video-assisted thoracic surgery were assigned randomly to either the nicorandil group or the nitroglycerin group. INTERVENTIONS Patients in the nicorandil group received a bolus dose of nicorandil, 0.08 mg/kg during induction of anesthesia, followed by a continuous infusion at a rate of 0.08 mg/kg/h. Patients in the nitroglycerin group received a continuous infusion of nitroglycerin at a rate of 1 µg/kg/min from the induction of anesthesia. MEASUREMENTS AND MAIN RESULTS Arterial blood gas analysis was performed at the following points: before induction of anesthesia; during TLV; at 5, 10, 20, and 30 minutes after the initiation of OLV. PaO2 at TLV (479.7 ± 57.1 v 408.2 ± 70.9 mmHg, p < 0.001); and at 5 minutes (344.8 ± 85.1 v 282.6 ± 85.8 mmHg, p = 0.012), 20 minutes (215.7 ± 103.0 v 158.2 ± 74.5 mmHg, p = 0.027), and 30 minutes (198.8 ± 103.5 v 147.5 ± 64.1 mmHg, p = 0.039) after OLV was significantly higher in the nicorandil group than in the nitroglycerin group. CONCLUSION This study demonstrated that oxygenation during TLV and OLV was significantly higher in patients receiving nicorandil than in those receiving nitroglycerin.