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Magnesium status and magnesium therapy in cardiac surgery: A systematic review and meta-analysis focusing on arrhythmia prevention.
Fairley, JL, Zhang, L, Glassford, NJ, Bellomo, R
Journal of critical care. 2017;:69-77
Abstract
PURPOSE To investigate magnesium as prophylaxis or treatment of postoperative arrhythmias in cardiac surgery (CS) patients. To assess impact on biochemical and patient-centered outcomes. MATERIALS AND METHODS We searched MEDLINE, CENTRAL and EMBASE electronic databases from 1975 to October 2015 using terms related to magnesium and CS. English-Language RCTs were included involving adults undergoing CS with parenterally administered magnesium to treat or prevent arrhythmias, compared to control or standard antiarrythmics. We extracted incidence of postoperative arrhythmias, termination following magnesium administration and secondary outcomes (including mortality, length of stay, hemodynamic parameters, biochemistry). RESULTS Thirty-five studies were included, with significant methodological heterogeneity. Atrial fibrillation (AF) was most commonly reported, followed by ventricular, supraventricular and overall arrhythmia frequency. Magnesium appeared to reduce AF (RR 0.69, 95% confidence interval (95%CI) 0.56-0.86, p=0.002), particularly postoperatively (RR 0.51, 95%CI 0.34-0.77, p=0.003) for longer than 24h. Maximal benefit was seen with bolus doses up to 60mmol. Magnesium appeared to reduce ventricular arrhythmias (RR=0.46, 95%CI 0.24-0.89, p=0.004), with a trend to reduced overall arrhythmias (RR=0.80, 95%CI 0.57-1.12, p=0.191). We found no mortality effect or significant increase in adverse events. CONCLUSIONS Magnesium administration post-CS appears to reduce AF without significant adverse events. There is limited evidence to support magnesium administration for prevention of other arrhythmias.
2.
QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors.
Ghatalia, P, Je, Y, Kaymakcalan, MD, Sonpavde, G, Choueiri, TK
British journal of cancer. 2015;(2):296-305
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Abstract
BACKGROUND Multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are known to cause cardiac toxicity, but the relative risk (RR) of QTc interval prolongation and serious arrhythmias associated with them are not reported. METHODS We conducted a trial-level meta-analysis of randomised phase II and III trials comparing arms with and without a US Food and Drug Administration-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib and regorafenib). A total of 6548 patients from 18 trials were selected. Statistical analyses were conducted to calculate the summary incidence, RR and 95% CIs. RESULTS The RR for all-grade and high-grade QTc prolongation for the TKI vs no TKI arms was 8.66 (95% CI 4.92-15.2, P<0.001) and 2.69 (95% CI 1.33-5.44, P=0.006), respectively, with most of the events being asymptomatic QTc prolongation. Respectively, 4.4% and 0.83% of patients exposed to VEGFR TKI had all-grade and high-grade QTc prolongation. On subgroup analysis, only sunitinib and vandetanib were associated with a statistically significant risk of QTc prolongation, with higher doses of vandetanib associated with a greater risk. The rate of serious arrhythmias including torsades de pointes did not seem to be higher with high-grade QTc prolongation. The risk of QTc prolongation was independent of the duration of therapy. CONCLUSIONS In the largest study to date, we show that VEGFR TKI can be associated with QTc prolongation. Although most cases were of low clinical significance, it is unclear whether the same applies to patients treated off clinical trials.