Continuous infusion versus intermittent bolus furosemide in ADHF: an updated meta-analysis of randomized control trials.

OBJECTIVE: Administering intermittent boluses of furosemide to patients with acute decompensated heart failure (ADHF) often leads to unfavorable hemodynamic changes. Continuous infusion may induce similar or greater diuresis without adverse hemodynamic consequences. We conducted a systemic review and meta-analysis of randomized clinical trials that compared the effects of continuous infusion and intermittent bolus of furosemide in patients hospitalized with ADHF. METHODS: We searched PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials databases from their inception until March 2011. Two investigators independently abstracted data on study characteristics, quality, and selected outcomes. Differences between investigators were resolved by mutual consensus. Comparisons were reported as the weighted mean difference (WMDs). RESULTS: Ten trials involving a total of 564 patients were included. When administered as a continuous infusion, furosemide resulted in greater diuresis (WMD, -240.54 mL/24 hours/100 mg furosemide; 95% confidence interval [CI], -462.42 to -18.66) and reduction in total body weight (WMD, -0.78 kg; 95% CI, -1.54 to -0.03), than when administered in intermittent boluses. Urinary sodium excretion (WMD, -20.26 mmol/24 hours; 95% CI, -60.48 to 19.96) and duration of hospital stay (WMD, 0.99 days; 95% CI, -2.08 to 4.06) were not different between the 2 groups. CONCLUSION: This meta-analysis showed statistical support for administering furosemide as a continuous infusion for greater diuresis and reduction in total body weight in patients hospitalized with ADHF. With the exception of greater diuresis, available data are homogenous for the reported outcomes but lack information on clinical endpoints. Larger studies are needed to provide robust recommendations for clinical practice.

Systematic review: comparing routine and selective invasive strategies for the acute coronary syndrome.

BACKGROUND: Patients with non-ST-segment elevation acute coronary syndrome (ACS) are managed with either a routine invasive strategy, in which all patients receive coronary angiography, or a selective invasive strategy, in which only patients with refractory or inducible ischemia receive coronary angiography. PURPOSE: To evaluate whether a routine invasive strategy improves cardiovascular outcomes more than a selective invasive strategy in patients with non-ST-segment elevation ACS. DATA SOURCES: English-language publications in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from 1966 to 18 September 2007. STUDY SELECTION: Two investigators independently reviewed searches and selected trials that compared death or myocardial infarction outcomes among adults with non-ST-segment elevation ACS by randomly assigning patients to either a routine invasive strategy or a selective invasive strategy. DATA EXTRACTION: Three investigators independently abstracted data from trial reports by using standardized forms. DATA SYNTHESIS: 10 trials with a total of 10,648 patients (mean age, 62 years; 71% male; median follow-up, 16.5 months) were found. Trial participants had typical symptoms of unstable angina and frequently had a positive electrocardiogram or marker evidence of myocardial ischemia. Of the 5330 participants assigned to the routine invasive strategy group, 847 had the composite outcome of death or nonfatal myocardial infarction, compared with 928 of 5318 participants assigned to the selective invasive strategy group (relative risk, 0.90 [95% CI, 0.74 to 1.08]). Four hundred thirty-eight patients in the routine invasive strategy group and 463 in the selective invasive strategy group died (relative risk, 0.95 [CI, 0.80 to 1.14]). Four hundred ninety and 569 nonfatal myocardial infarctions, respectively, occurred in the 2 groups (relative risk, 0.86 [CI, 0.68 to 1.08]). LIMITATIONS: Methodology, protocols, and outcome definitions differed substantially among the trials. The lower bound of the CI for the pooled results did not rule out the superiority of the routine invasive strategy. CONCLUSION: Available trial evidence is heterogeneous and insufficient for comparing routine and selective invasive strategies. Therefore, in patients with non-ST-segment elevation ACS a routine invasive strategy cannot be proven to reduce deaths or nonfatal myocardial infarction.

Effect of raloxifene therapy on venous thromboembolism in postmenopausal women. A meta-analysis.

Raloxifene, a selective estrogen receptor modulator, is indicated for the prevention of osteoporosis in postmenopausal women. However, its effect on the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) is unclear. Therefore, we conducted a meta-analysis to evaluate the effect of raloxifene on these outcomes. To identify randomized controlled trials of raloxifene, a systematic search of PubMed, EMBASE, and Cochrane Collaboration databases was performed from the date of inception of these databases to October 2007. Search was limited to trials that were published in peer-reviewed English-language medical journals. Articles were included in the meta-analysis if they had reported on DVT, PE, or thromboembolic events. Nine trials, including 24,523 postmenopausal women, (median age 59.4 years, range 55 to 67 years; median follow-up 24 months, range 3 to 67 months) met inclusion criteria. Therapy with raloxifene was associated with a 62% increase in odds of either DVT or PE (odds ratio = 1.62; 95% confidence interval = 1.25 to 2.09; p-value < 0.001). Similarly, raloxifene therapy was associated with 54% increase in odds of DVT (odds ratio = 1.54; 95% confidence interval = 1.13 to 2.11; p-value = 0.006) and 91% increase in odds of PE alone (odds ratio = 1.91;95% confidence interval = 1.05 to 3.47; p-value = 0.03). Raloxifene increases the risk of DVT and PE in postmenopausal women.

Meta-analysis of the effect of thiazolidinediones on serum C-reactive protein levels.

We conducted a meta-analysis of randomized clinical trials to evaluate the effect of thiazolidinediones on serum C-reactive protein levels. Compared with placebo, treatment with thiazolidinediones significantly decreased the serum C-reactive protein levels (mean -0.82 mg/L, 95% confidence interval -1.15 to -0.49 mg/L, p <0.0001). In a subgroup analysis, the effect of thiazolidinediones on the serum C-reactive protein levels was more pronounced in diabetic patients (mean -1.24 mg/L, 95% confidence interval -2.15 to -0.32 mg/L, p = 0.008) compared with nondiabetic patients (mean -0.27 mg/L, 95% confidence interval -0.41 to -0.14 mg/L, p <0.0001).

A meta-analysis of the effect of thiazolidinediones on blood pressure.

In epidemiologic studies, insulin resistance is associated with hypertension. Thiazolidinediones (TZDs) are antidiabetic agents that decrease insulin resistance. Multiple clinical trials have evaluated the effect of TZDs on blood pressure (BP) with inconsistent results. The aim of this study was to estimate the effect of TZDs on BP. The authors searched PubMed for clinical trials published in English. A total of 37 clinical trials that reported a change in BP were included in the analysis. Trials with independent-group design and trials with pre-post design were evaluated separately. When compared with baseline, TZDs lowered systolic BP by 4.70 mm Hg (95% confidence interval, -6.13 to -3.27) and diastolic BP by 3.79 mm Hg (95% confidence interval, -5.82 to -1.77). When compared with placebo, TZDs lowered systolic BP by 3.47 mm Hg (95% confidence interval, -4.91 to -2.02) and diastolic BP by 1.84 mm Hg (95% confidence interval, -3.43 to -0.25). Thus, TZDs lower both systolic and diastolic BP, albeit the BP-lowering effect is small and may not be of clinical significance.