Different dosage regimens of nifedipine, labetalol, and hydralazine for the treatment of severe hypertension during pregnancy: a network meta-analysis of randomized controlled trials.

OBJECTIVES: This network meta-analysis aimed to compare the efficacy and safety of intravenous (IV) hydralazine, oral nifedipine, and IV labetalol with different dosage regimens in the treatment of severe hypertension during pregnancy. METHODS: A comprehensive literature search was performed on PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) exploring the effects of hydralazine, nifedipine, and labetalol in the treatment of severe hypertension during pregnancy. RESULTS: A total of 21 RCTs with 2183 patients comparing 7 regimens (oral nifedipine 50,60,90 mg; hydralazine 15,25 mg; and labetalol 220,300 mg) were identified. Compared with IV labetalol 300 mg, nifedipine 50,60, and 90 mg significantly improved the successful treatment rate of severe hypertension during pregnancy, nifedipine 50 and 90 mg and IV hydralazine 25 mg required significantly fewer doses to achieve target blood pressure (BP), and nifedipine 50 mg took significantly shorter time to achieve target BP. Subgroup analysis showed that only nifedipine 50 mg tablets, not capsules, required a significantly shorter time and fewer doses to achieve target BP than IV labetalol 300 mg. Moreover, nifedipine 60,90 mg showed superior effectiveness than IV hydralazine 15,25 mg in the successful treatment rate of severe hypertension during pregnancy. SUCRA analysis suggested that nifedipine 50,60,90 mg as the better regimens with the lower rates of overall ADR and neonatal complications. CONCLUSION: These findings demonstrated the superiority of oral nifedipine 50,60,90 mg, especially oral nifedipine 50 mg tablets, in the treatment of severe hypertension during pregnancy than IV labetalol 300 mg, while oral nifedipine 60,90 mg also showed superiority in the successful treatment rate of severe hypertension during pregnancy than IV hydralazine 15,25 mg. However, the limitations of the underlying data indicate that future large-scale and rigorous RCTs are needed to confirm such findings.

Arctigenin Attenuates Ischemia/Reperfusion Induced Ventricular Arrhythmias by Decreasing Oxidative Stress in Rats.

BACKGROUND/AIMS: Arctigenin (ATG) has been shown to possess anti-inflammatory, immunemodulatory, anti-viral, anti-microbial, anti-carcinogenic, vasodilatory and anti-platelet aggregation properties. However, the protective role of ATG in prevention of arrhythmias induced by myocardial ischemia/reperfusion is unknown. The aim of this study was to investigate the anti-arrhythmia effect of ATG in an ischemia/reperfusion injured rat heart model and explore the related mechanisms. METHODS: Rats were randomly exposed to sham operation, myocardial ischemia/ reperfusion (MI/R) alone, ATG+ MI/R, pretreated with ATG in low (12.5 mg/kg/day), medium (50 mg/kg/day) and high dose (200 mg/kg/day), respectively. Ventricular arrhythmias were assessed. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde (MDA) in myocardial tissue were determined by chemical analysis. RESULTS: Compared to MI/R, rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/day showed significantly reduced incidence and duration of ventricular fibrillation, ventricular tachycardia and ventricular ectopic beat (VEB), and decreased the arrhythmia score during the 30-min ischemia. Incidence and duration of ventricular tachycardia, infarction size and arrhythmia scores in these groups were significantly decreased during the 120-min reperfusion. No ventricular fibrillation occurred during the period of reperfusion. Rats pretreated with ATG in doses of 50 mg/kg/day and 200 mg/kg/ day markedly enhanced the activities of antioxidant enzymes SOD and GSH-Px, reduced the level of MDA. No differences were observed between the group pretreated with a low dose of ATG and the sham group. Administration of ATG significantly increased the expression of antioxidant stress protein Nrf2, Trx1 and Nox1. CONCLUSION: Our data suggested that ATG plays anti-arrhythmia role in ischemia/reperfusion injury, which is probably associated with attenuating oxidative stress by Nrf2 signaling pathway.

Preventive effects of anisodamine against contrast-induced nephropathy in type 2 diabetics with renal insufficiency undergoing coronary angiography or angioplasty.

BACKGROUND: Anisodamine is widely used in therapy for treating acute glomerulonephritis and diabetic nephropathy because it can improve renal microcirculation. We performed a study to evaluate the preventive effects of anisodamine against contrast-induced nephropathy (CIN) in type 2 diabetics with renal insufficiency undergoing coronary angiography or angioplasty. METHODS: A total of 260 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) of 60 ml(-1)×min(-1)×1.73 m(-2) or less, who were undergoing coronary angiography or angioplasty, were randomly assigned to receive an infusion of either sodium chloride (control group, n = 128) or anisodamine (treatment group, n = 132). Patients in the treatment group received an infusion of anisodamine at a rate of 0.2 µg×kg(-1)×min(-1) from 12 hours before to 12 hours after coronary angiography or angioplasty, while patients in the control group received an infusion of sodium chloride with the same volume as the treatment group. All patients received intravenous sodium chloride hydration. CIN was defined as a 25% increase in serum creatinine from baseline or an absolute increase of > 0.5 mg/dl within three days after contrast exposure. The primary end point was the incidence of CIN. The secondary end point was a 25% or greater reduction in eGFR. RESULTS: There were no significant differences between the two groups with regard to age, gender, risk factors, laboratory results, medications and interventions. The incidence of CIN was 9.8% (13/132) in the treatment group and 20.3% (26/128) in the control group (P < 0.05). The secondary end point was 6.0% (8/132) in the treatment group and 16.4% (21/128) in the control group (P < 0.05). CONCLUSION: These results indicate the preventive effects of anisodamine against CIN in type 2 diabetics with renal insufficiency who are undergoing coronary angiography or angioplasty.

Safety and efficacy of anisodamine on prevention of contrast induced nephropathy in patients with acute coronary syndrome.

BACKGROUND: Previous studies have proved the renal protective effects of anisodamine in patients with septic shock. The aim of this study was to investigate anisodamine for the prevention of contrast induced nephropathy (CIN) in patients with acute coronary syndrome (ACS). METHODS: Consecutive ACS patients undergoing elective percutaneous coronary intervention (PCI) were randomly assigned to one of two groups: patients in the anisodamine group (ANI group) were assigned to receive intravenous infusions of anisodamine by an adjusted-dose (0.1 - 0.2 µg × kg(-1)× min(-1)) from the PCI procedure to 24 hours after PCI, and the control group (CON group) received 0.9% isotonic saline of the same volume. All patients were hydrated for 6 to 12 hours before and 12 hours after PCI. Blood samples were taken on the day of PCI and at 24, 48 and 72 hours after PCI to measure the serum creatinine (SCr). RESULTS: A total of 177 patients were involved in the study, 88 in the ANI group and 89 in the CON group. In both groups, the SCr concentrations significantly increased after PCI, with the peak value occurring at 48 hours. At 72 hours, the SCr concentration in the ANI group retuned to the baseline level (P > 0.05), but the SCr concentration in CON group was still higher than baseline level (P < 0.01). The SCr concentrations at 48 and 72 hours after PCI were much lower in the ANI group than those in the CON group (both P < 0.01). The estimated glomerular filtration rate (eGFR) significantly decreased after PCI, the lowest value occurred at 48 hours. In the ANI group, the eGFR at 72 hours was similar to the baseline level. In the CON group, the eGFR failed to return to baseline at 72 hours (P < 0.01). The eGFR at 24, 48 and 72 hours after PCI were higher in the ANI group (all P < 0.05). The incidence of CIN in the ANI group was lower than that in the CON group within 72 hours after PCI (P < 0.05). The results of multiple Logistic regression proved that both diabetes and left ventricular ejection fraction (LVEF) were independent predictors of CIN, and treatment with anisodamine was an independent preventive factor of CIN (OR 0.369 and 95%CI 0.171 to 0.794, P = 0.011). No serious side effects were found in the ANI group. CONCLUSION: Intravenous infusion of anisodamine during and after elective PCI may safely prevent the occurrence of CIN in ACS patients.