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Pharmacologic, Pharmacokinetic, and Therapeutic Differences among ACE Inhibitors

Angiotensin‐converting enzyme (ACE) inhibitors are a heterogeneous group of agents, and important pharmacologic, pharmacokinetic, and therapeutic differences among them must be understood to obtain optimal therapy. For patients with severe liver disease, lisinopril and captopril are not prodrugs (e.g., do not require hepatic activation), and lisinopril has almost solely renal elimination. Enalaprilat, the intravenous formulation of enalapril, is the only intravenously available ACE inhibitor and can be given to patients with severe liver dysfunction as it is also not a prodrug. Fosinopril is the only drug with compensatory dual routes of elimination, and it does not require dosage adjustment in patients with reduced renal function, as other ACE inhibitors do. Captopril and moexipril have potential drug‐food interactions and are the only agents that should be spaced from meals. The ACE inhibitors also differ in their dialyzability, half‐life, lipophilicity, trough:peak ratios, approved indications, and therapeutic information available for many indications.

Use of N-acetylcysteine to reduce post-cardiothoracic surgery complications: a meta-analysis

Post-cardiothoracic surgery (CTS) complications (e.g. myocardial injury, renal dysfunction, atrial fibrillation) may occur as a result of enhanced systemic inflammation, perhaps provoked by an oxidative stress response. N-acetylcysteine (NAC) is a free radical scavenger antioxidant agent that may attenuate this physiologic response and reduce post-CTS complications. Thus, a meta-analysis was performed to help characterize the potential beneficial effects of perioperative NAC administration in patients undergoing CTS. A systematic literature search in MEDLINE, EMBASE and the Cochrane Library was conducted through April 2008. A search strategy using medical subject headings and text keywords was performed. Results are reported as odds ratios or weighted mean differences with accompanying 95% confidence intervals (CIs). Studies were pooled using a fixed-effect model. The primary outcomes included atrial fibrillation (AF), myocardial infarction (MI), stroke, acute kidney injury (AKI), need for renal replacement therapy (RRT), mortality and total hospital length-of-stay (LOS). Upon meta-analysis of 13 trials (n=1338 subjects), the use of NAC appeared to statistically significantly lower the odds of developing post-CTS AF by 36% (95%CI 2-58%) (n=6 studies). This corresponded to an 8% (1-15%) pooled risk difference and a number-needed-to-treat of 13. NAC did not appear to significantly alter any of the other meta-analysis endpoints. The exclusion of the study utilizing only oral NAC therapy and the study with lower internal validity did not affect the overall conclusions of our meta-analysis. Currently, the most compelling data for using NAC in CTS patients is in post-CTS AF prevention. However, additional, larger randomized controlled trials evaluating this and other postoperative complication endpoints are needed.

The effect of testosterone on health‐related quality of life in elderly males – a pilot study

Objective: To assess the effect of short‐term testosterone supplementation on health‐related quality of life in elderly males.

A meta-analysis evaluating the impact of chitosan on serum lipids in hypercholesterolemic patients

Background/Objective: Chitosan is increasingly being used in the United States as an over-the-counter cholesterol-lowering agent. The positively charged amino groups of chitosan may have the ability to bind negatively charged molecules such as lipids and bile acids, inducing a greater fractional excretion in the feces. To better characterize the impact of chitosan on serum lipids in hypercholesterolemic patients, we performed a meta-analysis of randomized controlled trials. Methods: A systematic literature search of Medline, Embase, Cochrane Central and the Natural Medicines Comprehensive Database was conducted from the earliest possible date through May 2008. Trials were included in the analysis if they were randomized, placebo-controlled trials of chitosan in hypercholesterolemic patients and reported efficacy data on total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol or triglycerides. The weighted mean difference (WMD) of the change from baseline (in milligrams per deciliter) with 95% confidence interval was calculated as the difference between the mean in the chitosan and placebo groups using a random-effects model. Results: Six studies (n = 416 patients) met the inclusion criteria. Upon meta-analysis, the use of chitosan significantly lowered total cholesterol [WMD, –11.59 mg/dl (–21.45 to –1.73), p = 0.02] but not LDL cholesterol, HDL cholesterol or triglycerides. Conclusions: Based upon the currently available literature, we can only say that chitosan beneficially affects total cholesterol with 95% confidence. Additional, larger randomized controlled trials are needed to better characterize the effect of chitosan on other lipoproteins.

The impact of gender on survival amongst patients with implantable cardioverter defibrillators for primary prevention against sudden cardiac death

Background.  Implantable cardioverter defibrillators (ICDs) are a life‐saving therapy for many patients with cardiovascular disease at increased risk of fatal dysrhythmias. As men comprise the majority of the study population (67–92%) in clinical trials, the benefit to women is unknown. We performed a meta‐analysis of primary prevention trials to evaluate the impact of ICDs in men and women on death from any cause.

An evaluation of the change in electrocardiographic P-wave variables after acute caffeine ingestion in normal volunteers

Background: Caffeine’s effect on supraventricular dysrhythmias is poorly understood, and establishing a marker to predict atrial fibrillation may help to explain supraventricular dysrhythmias caused by caffeine.

Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis

CONTEXT: Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear. OBJECTIVE: To review the effectiveness of rhGH in the treatment of patients with CF. METHODS: Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high. RESULTS: Ten unique controlled trials (n = 312) and 8 observational studies (n = 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, health-related quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control. CONCLUSIONS: rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.

Antiplatelet agents for the prevention of arteriovenous fistula and graft thrombosis: a meta analysis

Aims:  The aim of this study was to evaluate the impact of antiplatelet agents on the thrombosis rates of arteriovenous fistulae and grafts used for haemodialysis access.

Association between statin therapy and reductions in atrial fibrillation or flutter and inappropriate shock therapy.

AIMS In patients without implantable cardioverter defibrillators (ICDs), statins have been shown to reduce the incidence of atrial fibrillation and atrial flutter (AF/AFL). We sought to determine if statin therapy could reduce the occurrence of AF/AFL with rapid ventricular rates with and without inappropriate shock therapy among a large heterogeneous ICD cohort. METHODS AND RESULTS We prospectively followed 1445 consecutive patients receiving an ICD for the primary (n = 833) or secondary (n = 612) prevention from December 1997 through January 2007. Outcome measures include incidence of AF/AFL that initiated ICD therapy or was detected during ICD interrogation. Cox hazard regression analyses were conducted to determine the predictors of AF/AFL with and without inappropriate shock delivery and did not include inappropriate shocks resulting from lead dysfunction or other exogenous factors. Patients in this study (n = 1445) were followed over a mean follow-up period of (mean +/- SD) 874 +/- 805 days. There were 563 episodes of AF/AFL detected, with 200 episodes resulting in inappropriate shock therapy. Overall, 745 patients received statin therapy and 700 did not. The use of statin therapy was associated with an adjusted hazard ratio of 0.472 [95% confidence interval (CI), 0.349-0.638, P < 0.001] for the development of AF/AFL with shock therapy and 0.613 (95% CI, 0.496-0.758, P < 0.001) without shock therapy when compared with the group without statin use. CONCLUSION Among a cohort with ICDs at high risk for cardiac arrhythmias, statin therapy was associated with a reduction in AF/AFL tachyarrhythmia detection and inappropriate shock therapy.

Effect of Nonergot Dopamine Agonists on Symptoms of Restless Legs Syndrome

PURPOSE We performed a meta-analysis of randomized placebo-controlled trials of nonergot dopamine agonists (NEDAs) for the treatment of restless legs syndrome. METHODS A systematic literature search was conducted through July 2007. The primary outcome measures assessed were the percentage of responders to medication as determined by the Clinical Global Impression-Improvement (CGI-I) scale and the adjusted mean change in the International Restless Legs Syndrome Study Group Scale (IRLS) score from baseline compared with placebo. Meta-regression analysis was performed to evaluate the impact of study duration on the primary outcomes. Safety endpoints were also evaluated. RESULTS A total of 14 trials (n = 3,197 subjects) were included in the meta-analysis. NEDA use resulted in greater response as measured by the CGI-I scale (relative risk [RR] 1.36; 95% CI, 1.24 to 1.49; P <.001), and greater reductions in IRLS scores (weighted mean difference [WMD] −4.93; 95% CI, −6.42 to −3.43; P <.001) from baseline vs placebo. Meta-regression analysis showed an inverse relationship between study duration and reduction in IRLS score. NEDAs were associated with a significant risk of adverse events (including nausea, dizziness, somnolence, and fatigue.) CONCLUSIONS Use of NEDAs in patients with moderate-to-severe restless legs syndrome results in significant reductions in symptom severity, but a significant portion of patients will discontinue their use as a result of adverse events.