Impact of magnesium sulfate on serum magnesium concentrations and intracellular electrolyte concentrations among patients undergoing radio frequency catheter ablation.

BACKGROUND: We evaluated the impact of intravenous magnesium on intracellular magnesium (iMg) and serum magnesium (sMg) in patients undergoing radio frequency catheter ablation (RFCA) for atrial fibrillation (AF). METHOD: Patients with AF received 4g intravenous magnesium sulfate or normal saline in a randomized, double-blinded fashion. Venous blood and buccal cells were collected for evaluation of sMg and iMg at baseline, postinfusion, at the end of ablation procedure and six-hours posttherapy. RESULTS: All subjects (n = 18) had baseline sMg within normal range but iMg concentrations below normal in 89% of subjects. Baseline sMg and iMg concentrations were similar between groups. After infusion, the magnesium group had significantly higher sMg concentration than the placebo group over the six hours. In contrast, iMg concentrations were significantly higher than placebo immediately after the infusion (P = 0.007) but not at the end of RFCA or six-hours postinfusion (P = 0.187 and P = 0.267). CONCLUSION: iMg deficiencies exist despite normal sMg concentrations in patients undergoing RFCA. Intravenous magnesium sulfate corrects iMg deficiencies immediately postinfusion.

Impact of amiodarone on the ability of anterior fat pad retention to prevent postcoronary arterial bypass grafting atrial fibrillation incidence: a substudy of the AFIST III (Atrial Fibrillation Suppression Trial III).

BACKGROUND: In the AFIST III (Atrial Fibrillation Suppressions Trial III), anterior fat pad (AFP) retention did not decrease the incidence of postoperative atrial fibrillation (POAF), but prophylaxis with amiodarone did. In order to examine the inter-relationship between amiodarone with AFP retention on POAF, we performed a planned subgroup analysis of AFIST III. METHODS: Coronary artery bypass graft (CABG) patients were randomized to AFP maintenance or removal with prophylactic amiodarone used via the discretion of the caregiver. Patients were categorized into four groups: AFP retention alone, AFP retention plus amiodarone, AFP removal alone and AFP removal plus amiodarone. Multivariate logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals for development of POAF. RESULTS: Amiodarone was used in 28% of the 178 patients (mean age = 66 +/- 10, 80% male, 5% previous atrial fibrillation) undergoing CABG surgery. The overall POAF occurrence rate, regardless of subgroup designation was 35.4%. On multivariate logistic regression, amiodarone plus AFP retention was associated with an 81% reduction in the odds of the patient developing POAF (p = 0.015). Amiodarone prophylaxis without AFP retention was associated with a 68% reduction (p = 0.040). CONCLUSION: Amiodarone prophylaxis with or without AFP retention is an independent negative predictor of POAF. Combining amiodarone with AFP retention may provide a synergistic effect in the prevention of POAF. Further studies are needed to validate the results of this study.

Impact of statins on risk of stroke: a meta-analysis.

BACKGROUND: Evidence from randomized, controlled trials suggests that reduction of low-density lipoprotein cholesterol with hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) therapy in patients at high risk for cardiovascular disease reduces the incidence of ischemic stroke; however, data from large epidemiologic observational studies suggest an inverse relationship between risk of hemorrhagic stroke and cholesterol levels. OBJECTIVE: To perform a meta-analysis of randomized controlled trials to assess the effect of statin therapy on all cerebrovascular events (CVEs), ischemic stroke, and hemorrhagic stroke. METHODS: A systematic literature search of MEDLINE, EMBASE, Cumulative Index to Nursing & Allied Health Literature, and Web of Science citations from June 1975 through September 2006 was performed to identify randomized controlled trials of statin therapy. Trials were included if they met the following criteria: (1) controlled clinical trials of statin therapy versus placebo, (2) well-described protocol, and (3) data reported on incidence of all CVEs, ischemic stroke, or hemorrhagic stroke. All data were independently extracted by 3 investigators. RESULTS: Weighted averages are reported as relative risk with 95% confidence intervals. A total of 26 trials (N = 100,560) reported incidence on all CVEs. Six trials (n = 37,292) reported incidence of ischemic stroke and 9 trials (n = 57,895) were included in the hemorrhagic stroke analysis. Statin therapy significantly reduced the risk of all CVEs (RR 0.83; 95% CI 0.76 to 0.91) and the risk of ischemic stroke (RR 0.79; 95% CI 0.63 to 0.99). Statin therapy did not significantly reduce risk of hemorrhagic stroke (RR 1.11; 95% CI 0.77 to 1.60). CONCLUSIONS: Statin therapy significantly reduces risk of developing all CVEs and ischemic stroke; however, it is associated with a nonsignificant increase in risk of hemorrhagic stroke.

Impact of statin dosing intensity on transaminase and creatine kinase.

PURPOSE: Higher intensity statin therapy reduces cardiovascular events more than lower intensity therapy, but the safety impact of higher intensity therapy is unknown. We performed a meta-analysis of randomized controlled trials comparing higher versus lower intensity therapy on liver and muscle safety. METHODS: A systematic literature search through January 2006 was conducted to identify randomized trials comparing higher versus lower intensity statin therapy meeting our criteria. Weighted averages were reported as relative risks (RRs) with 95% confidence intervals (random-effects model). Statistical heterogeneity scores were assessed with the Q statistic and L'Abbe plots. Publication bias was assessed with the Egger weighted regression and funnel plots. RESULTS: Higher intensity statin therapy increased the incidence of transaminase elevations (RR 3.10 [95% Confidence Interval [CI], 0.88-7.85]) versus lower intensity statin therapy. When studies of hydrophilic and lipophilic statins were evaluated separately, higher intensity hydrophilic statin therapy increased the risk for transaminase elevations (RR 3.54 [95% CI, 1.83-6.85]), but higher intensity lipophilic therapy did not (RR 1.58 [95% CI, 0.81-3.08]). The risk of creatine kinase (CK) elevations showed a trend toward an increase (RR 2.63 [95% CI, 0.88-7.85]) with higher intensity therapy. No occurrences of CK elevations occurred in studies evaluating hydrophilic statins, whereas lipophilic statins showed an increased risk with higher intensity therapy (RR 6.09 [95% CI, 1.36-27.35]). CONCLUSIONS: More aggressive statin therapy increases the incidence of transaminase elevations in clinical trials versus lower intensity therapy. Increases in transaminases may be more problematic when hydrophilic statins are used aggressively, whereas CK elevations are more problematic with higher intensity lipophilic statin therapy.

The use of protamine after radiofrequency catheter ablation: a pilot study.

OBJECTIVE: Evaluate the effect of administering intravenous protamine immediately post-radiofrequency catheter ablation (RFCA) on thrombotic and bleeding complications in heparinized patients. METHODS: Heparinized patients that had RFCA for atrial or ventricular arrhythmias at our institution between January 2001 and March 2006 and had a complete data set were included in this cohort evaluation. Patients receiving at least one dose of protamine within 15 min of RFCA were deemed the prophylactic group while those not receiving protamine within 15 min were the control group. Thrombotic (cerebrovascular event, transient ischemic attack, pulmonary embolism, deep vein thrombosis, or myocardial infarction) and bleeding events (blood loss requiring transfusion, hematoma requiring intervention, or intracranial hemorrhage) were compared between groups. RESULTS: Overall, 158 patients (74% male, 55 +/- 13.5) met inclusion criteria. Of these, 73.4% received prophylactic protamine (average dose = 39 mg +/- 17). Only one patient (0.9%) in the prophylactic protamine group and zero patients in the control group experienced a thrombotic event (p > 0.99). Only two patients (1.7%) in the protamine group (n = 2 blood transfusions) and zero patients in the control group experienced bleeding events (p = 0.839). CONCLUSIONS: Administering prophylactic intravenous protamine to allow for quicker catheter removal following RFCA in heparinized patients did not markedly impact thrombotic or bleeding complication rates in our population. The perceived benefit in our institution to protamine administration in this population is a reduction in postoperative patient immobilization and discomfort, reduced PACU nursing care, and earlier time to discharge. Given the low rate of thrombotic and bleeding events, a study of several thousand patients would be needed to fully evaluate the impact on these events.

Impact of epicardial anterior fat pad retention on postcardiothoracic surgery atrial fibrillation incidence: the AFIST-III Study.

OBJECTIVES: We conducted a randomized, blinded, controlled study evaluating the impact of anterior fat pad (AFP) maintenance on postoperative atrial fibrillation (POAF) incidence. BACKGROUND: Drugs with antiadrenergic effects reduce POAF. Because the epicardial AFP is parasympathetically innervated, its routine excision during coronary artery bypass grafting (CABG) might precipitate autonomic imbalance and induce POAF. METHODS: Patients (n = 180, mean age = 66 +/- 10 years, 80% men, 5% with previous atrial fibrillation) undergoing CABG surgery were randomized to either AFP maintenance or AFP removal. Routine prophylaxis against POAF with beta-blockers (85%) and amiodarone (28%) was allowed on the basis of caregivers' discretion. The development of POAF, total hospital costs, and heart rate variability was compared between groups. RESULTS: Anterior fat pad maintenance did not reduce POAF incidence (34.8% vs. 35.2%, p = 0.950) or total hospital costs (data as medians with 25%, 75% percentiles: 22,940 dollars [17,629 dollars, 29,274 dollars] vs. 23,866 dollars [18,602 dollars, 30,370 dollars], p = 0.647) but was associated with higher heart rate variability (SD of normal-to-normal RR intervals [SDNN]: 31.7 +/- 24.6 vs. 22.7 +/- 8.3, p = 0.05 and SD of all 5-min mean RR intervals [SDANN 5]: 17.1 +/- 11.9 vs. 10.1 +/- 5.5, p = 0.003) than AFP removal. CONCLUSIONS: Maintaining the AFP prevents attenuation of parasympathetic tone after CABG but does not reduce POAF or total hospital costs in any appreciable way.

Thiazolidinediones and risk of repeat target vessel revascularization following percutaneous coronary intervention: a meta-analysis.

OBJECTIVE: Thiazolidinediones (TZDs) (rosiglitazone and pioglitazone) are a class of antidiabetes agents that have a high affinity for peroxisome proliferator-activated receptor-gamma. TZDs initiate a multitude of physiologic processes that may elicit benefits as systemic agents for the prevention of restenosis requiring revascularization following percutaneous coronary intervention (PCI). Numerous trials have evaluated the impact of TZDs on repeat target vessel revascularization (TVR) in patients following PCI; however, several limitations (small sample size, inconclusive results, and risk factor stratification) complicate definitive conclusions. A meta-analysis was performed to evaluate the impact of TZDs on repeat TVR following PCI. RESEARCH DESIGN AND METHODS: Included trials met the following criteria: 1) prospective, randomized controlled trials evaluating available TZDs versus standards of care; 2) well-described protocol; 3) minimum of 6 months of follow-up; and 4) data provided on repeat TVR. Data are presented as relative risks (RRs) with 95% CIs. RESULTS: Seven clinical trials (n = 608) met the inclusion criteria. Upon meta-analysis, the risk of repeat TVR was significantly reduced in patients who received TZD therapy compared with standards of care (RR 0.35 [95% CI 0.22-0.57]). In studies using rosiglitazone (0.45 [0.25-0.83]) and pioglitazone (0.24 [0.11-0.51]), risk of repeat TVR was significantly reduced. Risk of repeat TVR was also significantly reduced among patients with (0.34 [0.19-0.63]) and without (0.37 [0.18-0.77]) diabetes. CONCLUSIONS: Results from this meta-analysis suggest that TZDs effectively reduce the risk of repeat TVR following PCI.

An evaluation of the impact of oral magnesium lactate on the corrected QT interval of patients receiving sotalol or dofetilide to prevent atrial or ventricular tachyarrhythmia recurrence.

BACKGROUND: Intravenous magnesium reduces the QTc interval of patients receiving ibutilide. Whether oral magnesium can reduce the QTc interval associated with oral sotalol and dofetilide is not known. This study was undertaken to evaluate the impact of oral magnesium on the QTc interval and whether an inherent intracellular magnesium deficiency exists among patients with arrhythmias. METHODS: Participants receiving sotalol or dofetilide for atrial or ventricular arrhythmias were randomized to receive magnesium l-lactate (504 mg elemental magnesium daily, Niche Pharmaceuticals, Roanoke, TX) or placebo for 48 hours. A 12-lead electrocardiogram (ECG) was obtained at baseline, 3 hours, and 51 hours after dosing to correspond to the Tmax after oral ingestion. The QTc interval was measured from the ECGs and compared between groups. Intracellular magnesium concentrations were determined by energy-dispersive x-ray analysis at baseline and 51 hours after dosing (Intracellular Diagnostics, Inc., Foster City, CA). RESULTS: The QTc interval reductions from baseline were greater in the magnesium group than placebo at 3 and 51 hours (P = 0.015 and P < 0.001, respectively). Sixty-three percent of patients (regardless of experimental group) had baseline intracellular magnesium concentrations below the normal reference range of 33.9-41.9 mEq/IU, with an average level of 32.6 +/- 2.2 mEq/IU. CONCLUSIONS: Oral magnesium l-lactate raises intracellular magnesium concentrations and lowers the QTc interval of patients receiving sotalol or dofetilide.

Statins and cancer risk: a meta-analysis.

CONTEXT: Statins are cholesterol-lowering drugs that have been proven in randomized controlled trials to prevent cardiac events. Recent retrospective analyses have suggested that statins also prevent cancer. OBJECTIVES: To investigate the effect of statin therapy on cancer incidence and cancer death and to analyze the effect of statins on specific cancers and the effect of statin lipophilicity or derivation. DATA SOURCES: A systematic literature search of MEDLINE, EMBASE, CINAHL, Web of Science, CANCERLIT, and the Cochrane Systematic Review Database through July 2005 was conducted using specific search terms. A review of cardiology and cancer abstracts and manual review of references was also performed. STUDY SELECTION: Twenty-seven of the 8943 articles (n = 86,936 participants) initially identified met the inclusion criteria, reporting 26 randomized controlled trials of statins, with a mean duration of follow-up of at least 1 year, enrolling a minimum of 100 patients, and reporting data on either cancer incidence (n = 20 studies) or cancer death (n = 22 studies). DATA EXTRACTION: All data were independently extracted by 3 investigators using a standardized data abstraction tool. Weighted averages were reported as odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model (DerSimonian and Laird methods). Statistical heterogeneity scores were assessed with the Q statistic. DATA SYNTHESIS: In meta-analyses including 6662 incident cancers and 2407 cancer deaths, statins did not reduce the incidence of cancer (OR, 1.02; 95% CI, 0.97-1.07) or cancer deaths (OR, 1.01; 95% CI, 0.93-1.09). No reductions were noted for any individual cancer type. This null effect on cancer incidence persisted when only hydrophilic, lipophilic, naturally derived, or synthetically derived statins were evaluated. CONCLUSIONS: Statins have a neutral effect on cancer and cancer death risk in randomized controlled trials. We found that no type of cancer was affected by statin use and no subtype of statin affected the risk of cancer.

Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis.

Postoperative atrial fibrillation can occur in 25% to 40% of patients undergoing cardiothoracic surgery. Although the majority of postoperative atrial fibrillation is benign, it has been associated with prolonged hospital length of stay. Magnesium prophylaxis against postoperative atrial fibrillation has been evaluated in several clinical trials; however these trials were small in size and therefore conveyed mixed or inconclusive results. In an attempt to better understand magnesium's role in this setting, we conducted a meta-analysis. A systematic literature search was conducted from January 1999 through August 2004 to identify trials of prophylactic magnesium in the setting of cardiothoracic surgery. The primary outcome measure was the incidence of postoperative atrial fibrillation. Trials were further analyzed based on cumulative doses of magnesium and perioperative time of initiation of prophylaxis, as well as length of stay. Seven randomized trials were identified. Upon meta-analysis, magnesium was found to prevent postoperative atrial fibrillation with an odds ratio of 0.66 and 95% confidence interval of 0.51 to 0.87. The incidence of postoperative atrial fibrillation was also significantly reduced in the low dose with an odds ratio of 0.36 and 95% confidence interval of 0.23 to 0.56, and in the preoperative groups with an odds ratio of 0.46 and 95% confidence interval of 0.31 to 0.67. Prophylactic magnesium reduced length of stay (n = 6 studies) by a weighted mean difference of 0.29 days, with a 95% confidence interval 0.54 to 0.05. Prophylactic magnesium reduced cardiothoracic surgery patients' risk of postoperative atrial fibrillation and length of stay. Administering lower doses and initiating prophylaxis in the preoperative period achieved the greatest reduction in postoperative atrial fibrillation.