The Effect of Black Tea on Blood Pressure: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

Objective

Epidemiological evidence has linked consumption of black tea, produced from Camellia sinensis, with a reduced risk of cardiovascular diseases. However, intervention studies on the effects of tea consumption on blood pressure (BP) have reported inconsistent results. Our objective was to conduct a systematic literature review with meta-analysis of controlled human intervention studies examining the effect of tea consumption on BP.

Methods

We systematically searched Medline, Biosis, Chemical Abstracts and EMBASE databases through July 2013. For inclusion, studies had to meet the following pre-defined criteria: 1) placebo controlled design in human adults, 2) minimum of 1 week black tea consumption as the sole intervention, 3) reported effects on systolic BP (SBP) or diastolic BP (DBP) or both. A random effects model was used to calculate the pooled overall effect of black tea on BP.

Results

Eleven studies (12 intervention arms, 378 subjects, dose of 4–5 cups of tea) met our inclusion criteria. The pooled mean effect of regular tea ingestion was −1.8 mmHg (95% CI: −2.8, −0.7; P = 0.0013) for SBP and −1.3 mmHg (95% CI: −1.8, −0.8; P<0.0001) for DBP. In covariate analyses, we found that the method of tea preparation (tea extract powders versus leaf tea), baseline SBP and DBP, and the quality score of the study affected the effect size of the tea intervention (all P<0.05). No evidence of publication bias could be detected.

Conclusions

Our meta-analysis indicates that regular consumption of black tea can reduce BP. Although the effect is small, such effects could be important for cardiovascular health at population level.     

Effect of Fruit Juice on Cholesterol and Blood Pressure in Adults: A Meta-Analysis of 19 Randomized Controlled Trials

Background

The effect of fruit juice on serum cholesterol and blood pressure in humans has generated inconsistent results. We aimed to quantitatively evaluate the effect of fruit juice on serum cholesterol and blood pressure in adults.

Methods

We performed a strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to October, 2012) for randomized controlled trials that evaluated the effects of fruit juice on serum cholesterol and blood pressure. Study quality was assessed by using the Jadad scale. Weighted mean differences were calculated for net changes in cholesterol and blood pressure by using fixed-effects model. Prespecified subgroup and sensitivity analyses were conducted to explore the potential heterogeneity.

Results

Nineteen trials comprising a total of 618 subjects were included in this meta-analysis. Fruit juice consumption borderlinely reduced the diastolic blood pressure (DBP) by 2.07 mm Hg (95% CI: −3.75, −0.39 mm Hg; p = 0.02), but did not show significant effects on total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) concentrations or systolic blood pressure (SBP) values. A significant reduction of TC concentration was observed in low-median intake of total polyphenols group. Subgroup analyses for HDL-C and LDL-C concentrations did not show statistically significant results. No significant heterogeneity was detected for all the measures.

Conclusion

This meta-analysis suggested that fruit juice had a borderline significant effect on reducing DBP, but had no effect on TC, HDL-C, LDL-C concentrations or SBP.     

Effect of Black Tea Consumption on Blood Cholesterol: A Meta-Analysis of 15 Randomized Controlled Trials

Background

The results of the studies that have investigated the effects of black tea on blood cholesterol are inconsistent. The aim of this study is to quantitatively assess the effects of black tea on cholesterol concentrations.

Methods

PubMed, Embase, MEDLINE, and Cochrane Library (through to July 2014) were searched for randomized controlled trials (RCTs) designed to investigate the effect of black tea on blood cholesterol concentrations. The study quality was assessed by the Jadad scoring criteria. Pooled effect of black tea consumption on blood cholesterol concentrations was evaluated by fixed-effects or random-effects model. Meta-regression analyses were conducted to estimate dose effects of black tea polyphenols on concentrations of blood cholesterol. Subgroup and sensitivity analyses were performed to assess the potential source of heterogeneity.

Results

The consumption of black tea did not significantly lower TC concentrations either in healthy subjects or patients with coronary artery diseases based on both fixed-effects and random-effects analysis. No significant change was observed in HDL-C concentrations in healthy participants or in subjects with coronary artery disease supplemented with black tea when compared with control participants. The pooled net change of LDL-C in healthy participants was −5.57 mg/dL (95% CI, −9.49 to −1.66 mg/dL; P = 0.005) in fixed-effects analysis and −4.56 (95% CI, −10.30 to 1.17 mg/dL; P = 0.12) in random-effects analysis. No significant net change was observed in LDL-C concentrations in patients with coronary artery disease. Subgroup and sensitivity did not significantly influence the overall outcomes of this meta-analysis. No significant dose effects of black tea polyphenols on blood cholesterol concentrations were detected in meta-regression analyses.

Conclusion

The meta-analysis suggests that the consumption of black tea might not have beneficial effects on concentrations of TC, HDL-C, and LDL-C. Further high quality RCTs are needed to definitively draw a causal interpretation of the findings.     

Effect of Antioxidant Vitamin Supplementation on Cardiovascular Outcomes: A Meta-Analysis of Randomized Controlled Trials

Background

Antioxidant vitamin (vitamin E, beta-carotene, and vitamin C) are widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamin on cardiovascular events remains unclear.

Methodology and Principal Findings

We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant literature. Eligible studies were randomized controlled trials that reported on the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo. Outcomes analyzed were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any possible adverse events. We used the I² statistic to measure heterogeneity between trials and calculated risk estimates for cardiovascular outcomes with random-effect meta-analysis. Independent extraction was performed by two reviewers and consensus was reached. Of 293 identified studies, we included 15 trials reporting data on 188209 participants. These studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation as compared to placebo had no effect on major cardiovascular events (RR, 1.00; 95%CI, 0.96–1.03), myocardial infarction (RR, 0.98; 95%CI, 0.92–1.04), stroke (RR, 0.99; 95%CI, 0.93–1.05), total death (RR, 1.03; 95%CI, 0.98–1.07), cardiac death (RR, 1.02; 95%CI, 0.97–1.07), revascularization (RR, 1.00; 95%CI, 0.95–1.05), total CHD (RR, 0.96; 95%CI, 0.87–1.05), angina (RR, 0.98; 95%CI, 0.90–1.07), and congestive heart failure (RR, 1.07; 95%CI, 0.96 to 1.19).

Conclusion/Significance

Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.     

Effect of B-vitamin Supplementation on Stroke: a Meta-Analysis of Randomized Controlled Trials

Background

B vitamins have been extensively used to reduce homocysteine levels; however, it remains uncertain whether B vitamins are associated with a reduced risk of stroke. Our aim was to evaluate the effects of B vitamins on stroke.

Methodology and Principal findings

We systematically searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials to identify studies for our analysis. Relative risk (RR) was used to measure the effect of B-vitamin supplementation on the risk of stroke. The analysis was further stratified based on factors that could affect the treatment effects. Of the 13,124 identified articles, we included 18 trials reporting data on 57,143 individuals and 2,555 stroke events. B-vitamin supplementation was not associated with a significant reduction in the risk of stroke (RR, 0.91, 95%CI: 0.82–1.01, P = 0.075; RD, -0.003, 95%CI: -0.007–0.001, P = 0.134). Subgroup analyses suggested that B-vitamin supplementation might reduce the risk of stroke if included trials had a man/woman ratio of more than 2 or subjects received dose of folic acid less than 1 mg. Furthermore, in a cumulative meta-analysis for stroke, the originally proposed nonsignificant B-vitamin effect was refuted by the evidence accumulated up to 2006. There is a small effect with borderline statistical significance based on data gathered since 2007.

Conclusions/Significance

Our study indicates that B-vitamin supplementation is not associated with a lower risk of stroke based on relative and absolute measures of association. Subgroup analyses suggested that B-vitamin supplementation can effectively reduce the risk of stroke if included trials had a man/woman ratio of more than 2 or subjects received dose of folic acid less than 1 mg.     

The Effect of Statins on Mortality in Septic Patients: A Meta-Analysis of Randomized Controlled Trials

Objective

Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay.

Data sources and study selection

Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients.

Data extraction and synthesis

Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found.

Conclusions

Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic.     

Effect of Low-Frequency rTMS on Aphasia in Stroke Patients: A Meta-Analysis of Randomized Controlled Trials

Background

Small clinical trials have reported that low-frequency repetitive transcranial magnetic stimulation (rTMS) might improve language recovery in patients with aphasia after stroke. However, no systematic reviews or meta-analyses studies have investigated the effect of rTMS on aphasia. The objective of this study was to perform a meta-analysis of studies that explored the effects of low-frequency rTMS on aphasia in stroke patients.

Methods

We searched PubMed, CENTRAL, Embase, CINAHL, ScienceDirect, and Journals@Ovid for randomized controlled trials published between January 1965 and October 2013 using the keywords “aphasia OR language disorders OR anomia OR linguistic disorders AND repetitive transcranial magnetic stimulation OR rTMS”. We used fixed- and random-effects models to estimate the standardized mean difference (SMD) and a 95% CI for the language outcomes.

Results

Seven eligible studies involving 160 stroke patients were identified in this meta-analysis. A significant effect size of 1.26 was found for the language outcome severity of impairment (95% CI = 0.80 to 1.71) without heterogeneity (I² = 0%, P = 0.44). Further analyses demonstrated prominent effects for the naming subtest (SMD = 0.52, 95% CI = 0.18 to 0.87), repetition (SMD = 0.54, 95% CI = 0.16 to 0.92), writing (SMD = 0.70, 95% CI = 0.19 to 1.22), and comprehension (the Token test: SMD = 0.58, 95% CI = 0.07 to 1.09) without heterogeneity (I² = 0%). The SMD of AAT and BDAE comprehension subtests was 0.32 (95% CI = −0.08 to 0.72) with moderate heterogeneity (I² = 32%,P = 0.22). The effect size did not change significantly even when any one trial was eliminated. None of the patients from the 7 included articles reported adverse effects from rTMS.

Conclusions

Low-frequency rTMS with a 90% resting motor threshold that targets the triangular part of the right inferior frontal gyrus (IFG) has a positive effect on language recovery in patients with aphasia following stroke. Further well-designed studies with larger populations are required to ascertain the long-term effects of rTMS in aphasia treatment.     

Dezocine for Preventing Postoperative Pain: A Meta-Analysis of Randomized Controlled Trials

Background

Dezocine is considered to be an alternative medication for managing postoperative pain. The aim of this study was to assess the efficacy and safety of this drug in this regard.

Methods

Medline, EMBASE and the Cochrane Central Register of Control Trials (CENTRAL) were searched to identify all randomized controlled trials (RCTs) that compare dezocine with placebo or dezocine with morphine on postoperative pain. The data were extracted and pooled using Mantel-Haenszel random effects model. Heterogeneity was tested using the I ² statistic with values >50% and Chi² test with P ≤ 0.05 indicating obvious heterogeneity between the studies.

Results

Seven trials evaluating 665 patients were included. The number of patients with at least 50% pain relief was increased (N = 234; RR 3.04, 95% CI 2.27 to 4.08) and physician (N = 465; RR 2.84, 95% CI 1.66 to 4.84) and patient satisfaction (N = 390; RR 2.81, 95% CI 1.85 to 4.26) were improved following the administration of dezocine compared with the placebo. The effects of dezocine were similar to those of morphine in terms of the number of patients reporting at least 50% pain relief within 2–6 h after surgery (N = 235; RR 1.29, 95% CI 1.15 to 1.46) and physician (N = 234; RR 1.18, 95% CI 0.93 to 1.49) and patient (N = 158; RR 1.33, 95% CI 0.93 to 1.92) satisfaction. While, the number of patients with at least 50% pain relief within 0–1 h after surgery increased following dezocine compared with morphine treatment (N = 79; RR 1.45, 95% CI 1.18 to 1.77). There was no difference in the incidence of postoperative nausea and vomiting (PONV) following dezocine treatment compared with the placebo (N = 391; RR 1.06, 95% CI 0.42 to 2.68) or morphine treatment (N = 235; RR 0.65, 95% CI 0.14 to 2.93).

Conclusion

Dezocine is a promising analgesic for preventing postoperative pain, but further studies are required to evaluate its safety.     

Prevention Effect of Allopurinol on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Meta-Analysis of Prospective Randomized Controlled Trials

Background

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs) have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP). However, these results remained controversial.

Objective

To conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP.

Methods

Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ² test with the significance set P<0.10 or I²>50%.

Results

Six RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986) and 9.9%(98/988) respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39–1.42) with significant heterogeneity (I² = 70.4%, P = 0.005). When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (I_moderate ² = 82.3%, P_moderate = 0.018). Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (I_mild ² = 62.8%, P_mild = 0.068).

Conclusion

The prophylactic use of allopurinol in different dosages and administration time had no effect in preventing incidence and severity of PEP.     

Effect of Clazosentan in Patients with Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

Background

Cerebral vasospasm is the most important potentially treatable cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (aSAH). Clazosentan, a selective endothelinreceptor antagonist, has been suggested to help reduce the incidence of vasospasm in patients with aSAH. However, the results were controversial in previous trials. This meta-analysis attempts to assess the effect of clazosentan in patients with aSAH.

Methodology/Principal Findings

We systematically searched Pubmed, Embase, and the Cochrane Library from their inception until June, 2012. All randomized controlled trials (RCTs) related to the effect of clazosentan in aSAH were included. The primary outcomes included the incidence of angiographic vasospasm, new cerebral infarction (NCI), delayed ischemic neurological deficits (DIND), and vasospasm-related morbidity/mortality (M/M); the second outcomes included the occurrence of rescue therapy, all-cause-mortality, and poor outcome. 4 RCTs were included with a total of 2156 patients. The risk of angiographic vasospasm (relative risk [RR] = 0.58; 95% CI, 0.48 to 0.71), DIND (RR = 0.76; 95% CI, 0.62 to 0.92), and vasospasm-related M/M (RR = 0.80; 95% CI, 0.67 to 0.96) were statistically significantly reduced in the clazosentan group. Patients treated with clazosentan had a reduced occurrence of rescue therapy (RR = 0.62; 95% CI, 0.49 to 0.79). However, no statistically significant effects were observed in NCI (RR = 0.74; 95% CI, 0.52 to 1.04), mortality (RR = 1.03; 95% CI, 0.71 to 1.49), and poor outcome (RR = 1.12; 95% CI, 0.96 to 1.30).

Conclusions/Significance

Our pooling data supports that clazosentan is probably effective in preventing the occurrence of angiographic vasospasm, vasospasm-related DIND, vasospasm related M/M, and rescue therapy. However, no evidence lends significant supports to the benefits of clazosentan in decreasing the occurrence of NCI, mortality or improving the functional outcome.     

Pharmacogenetics-Based versus Conventional Dosing of Warfarin: A Meta-Analysis of Randomized Controlled Trials

Background

Recently, using the patient’s genotype to guide warfarin dosing has gained interest; however, whether pharmacogenetics-based dosing (PD) improves clinical outcomes compared to conventional dosing (CD) remains unclear. Thus, we performed a meta-analysis to evaluate these two strategies.

Methods

The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese VIP and Chinese Wan-fang databases were searched. The Cochrane Collaboration’s tool was used to assess the risk of bias in randomized controlled trials (RCTs). The primary outcome was time within the therapeutic range (TTR); the secondary end points were the time to maintenance dose and time to first therapeutic international normalized ratio (INR), an INR greater than 4, adverse events, major bleeding, thromboembolism and death from any cause.

Results

A total of 11 trials involving 2,678 patients were included in our meta-analysis. The results showed that PD did not improve the TTR compared to CD, although PD significantly shortened the time to maintenance dose (MD = -8.80; 95% CI: -11.99 to -5.60; P<0.00001) and the time to first therapeutic INR (MD = -2.80; 95% CI: -3.45 to -2.15; P<0.00001). Additionally, PD significantly reduced the risk of adverse events (RR = 0.86; 95% CI: 0.75 to 0.99; P = 0.03) and major bleeding (RR = 0.36; 95% CI: 0.15 to 0.89, P = 0.03), although it did not reduce the percentage of INR greater than 4, the risk of thromboembolic events and death from any cause. Subgroup analysis showed that PD resulted in a better improvement in the endpoints of TTR and over-anticoagulation at a fixed initial dosage rather than a non-fixed initial dosage.

Conclusions

The use of genotype testing in the management of warfarin anticoagulation was associated with significant improvements in INR-related and clinical outcomes. Thus, genotype-based regimens can be considered a reliable and accurate method to determine warfarin dosing and may be preferred over fixed-dose regimens.

Trial Registration PROSPERO

Database registration: CRD42015024127.     

Merocel versus Nasopore for Nasal Packing: A Meta-Analysis of Randomized Controlled Trials

Objective

To compare the clinical outcomes, including efficacy and complications, of Merocel versus Nasopore as a nasal packing material after nasal surgery.

Methods

Relevant randomized controlled trials were identified from electronic databases (The Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure and Chinese Biomedical Database). Conference proceedings and references from identified trials and review articles were also searched. Outcome measures were pain during nasal packing, pain and bleeding upon packing removal, pressure sensation, nasal blockage, formation of synechiae, mucosal healing, and patients'' general satisfaction.

Results

Seven randomized controlled trials met criteria for analysis. Compared with Merocel, Nasopore significantly reduced patients'' subjective symptoms including in situ pain (pain experienced while packing is in place), nasal pressure, pain and bleeding during packing removal, and increased patients'' general satisfaction with nasal packing. There were no significant differences in nasal obstruction, adhesion and mucosal healing between the Merocel and Nasopore groups.

Conclusions

Preliminary evidence suggests that Nasopore may be superior to Merocel as a nasal packing material with regard to in situ pain, pain and bleeding upon removal, pressure, and general satisfaction and does not differ from Merocel in terms of nasal obstruction, tissue adhesion, and long-term mucosal healing.     

Effect of Combination Therapy on Joint Destruction in Rheumatoid Arthritis: A Network Meta-Analysis of Randomized Controlled Trials

Background

Despite significant cost differences, the comparative effect of combination treatments of disease modifying anti-rheumatic drugs (DMARDs) with and without biologic agents has rarely been examined. Thus we performed a network meta-analysis on the effect of combination therapies on progression of radiographic joint erosions in patients with rheumatoid arthritis (RA).

Methods and Findings

The following combination drug therapies compared versus single DMARD were investigated: Double DMARD: 2 DMARDs (methotrexate, sulfasalazine, leflunomide, injectable gold, cyclosporine, chloroquine, azathioprin, penicillamin) or 1 DMARD plus low dose glucocorticoid (LDGC); triple DMARD: 3 DMARDs or 2 DMARDs plus LDGC; biologic combination: 1 DMARD plus biologic agent (tumor necrosis factor α inhibitor (TNFi) or abatacept or tocilizumab or CD20 inhibitor (CD20i)). Randomized controlled trials were identified in a search of electronic archives of biomedical literature and included in a star-shaped network meta-analysis and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. Effects are reported as standardized mean differences (SMD). The effects of data from 39 trials published in the period 1989–2012 were as follows: Double DMARD: −0.32 SMD (CI: −0.42, −0.22); triple DMARD: −0.46 SMD (CI: −0.60, −0.31); 1 DMARD plus TNFi: −0.30 SMD (CI: −0.36, −0.25); 1 DMARD plus abatacept: −0.20 SMD (CI: −0.33, −0.07); 1 DMARD plus tocilizumab: −0.34 SMD (CI: −0.48, −0.20); 1 DMARD plus CD20i: −0.32 SMD (CI: −0.40, −0.24). The indirect comparisons showed similar effects between combination treatments apart from triple DMARD being significantly better than abatacept plus methotrexate (−0.26 SMD (CI: −0.45, −0.07)) and TNFi plus methotrexate (−0.16 SMD (CI: −0.31, −0.01)).

Conclusion

Combination treatment of a biologic agent with 1 DMARD is not superior to 2–3 DMARDs including or excluding LDGC in preventing structural joint damage. Future randomized studies of biologic agents should be compared versus a combination of DMARDs.     

Effect of Pioglitazone on In-Stent Restenosis after Coronary Drug-Eluting Stent Implantation: A Meta-Analysis of Randomized Controlled Trials

Background

In-stent restenosis (ISR) remains a common life-threatening complication and some studies have shown that pioglitazone can reduce the incidence of ISR in patients with drug-eluting stents (DES) implantation. We conducted a meta-analysis to assess the effect of pioglitazone in preventing ISR after DES implantation.

Methods

Randomized controlled trials (RCTs) investigating the effects of pioglitazone for ISR after DES implantation were identified by systematic searches of multiple online databases and manual searches of related reference lists of identified trials through May 2014. The primary endpoint was the rate of ISR. Secondary endpoints included minimum lumen diameter, percentage stenosis of stented vessels, late loss, in-stent neointimal volume, target vessel revascularization (TVR), target lesion revascularization, myocardial infarction, stent thrombosis and death.

Results

Five studies, comprising 255 pioglitazone-treated patients and 245 controls, were identified in the current meta-analysis. Pioglitazone did not significantly reduce the rate of ISR (P = 0.20) with low heterogeneity (I² = 13.3%, P = 0.32). For the secondary outcomes, pioglitazone did not substantially affect the pooled estimates of these endpoints except late loss (P = 0.01) and TVR (P = 0.04).

Conclusions

The limited evidence indicates that pioglitazone does not demonstrate markedly beneficial effect in patients subjected to coronary DES implantation. However, the results should be interpreted with care given the small sample size. Further large-scale RCTs are needed.     

Bleeding Risk and Mortality of Edoxaban: A Pooled Meta-Analysis of Randomized Controlled Trials

Objective(s)

Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unexplored.

Methods

Medline, Embase and Web of Science were searched to March 8, 2014 for prospective, randomized controlled trials (RCTs) that assessed the safety profile of edoxaban with warfarin. Safety outcomes examined included bleeding risk and mortality.

Results

Five trials including 31,262 patients that met the inclusion criteria were pooled. Overall, edoxaban was associated with a significant decrease in major or clinically relevant nonmajor bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74 to 0.82, p<0.001] and any bleeding events [RR 0.82, 95% CI 0.79 to 0.85, p<0.001]. Edoxaban also showed superiority to warfarin both in all-cause mortality [RR 0.92, 95% CI0.85 to0.99, p = 0.02] and cardiovascular mortality [RR 0.87, 95% CI0.79 to 0.96, p = 0.004]. Subgroup analyses indicated that RRs of edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p = 0.004) respectively in major or clinically relevant nonmajor bleeding; 0.71 (p<0.001), 0.89 (p<0.001) and 2.29 (p = 0.002) respectively in any bleeding; as well as 0.86 (p = 0.01), 0.87 (p = 0.01) and 0.28 (p = 0.41) respectively in cardiovascular death… Meanwhile, paramount to note that pooled results other than the largest trial showed edoxaban was still associated with a decrease in the rate of major or clinically relevant nonmajor bleeding event (p = 0.02) and any bleeding (p = 0.002), but neither in all-cause death (p = 0.66) nor cardiovascular death (p = 0.70).

Conclusions

Edoxaban, a novel orally available direct factor Xa inhibitor, seems to have a favorable safety profiles with respect to bleeding risk and non-inferior in mortality when compared to warfarin. Further prospective RCTs are urgently needed to confirm the results of this meta-analysis.     

Single Incision versus Conventional Laparoscopic Cholecystectomy Outcomes: A Meta-Analysis of Randomized Controlled Trials

Background

Previous meta-analyses that compared the outcome of SILC and CLC have not presented consistent conclusions. This meta-analysis was performed after adding many recent RCTs, to clarify this issue.

Methods

Relevant articles published in English were identified by searching PubMed, Embase, Web of Knowledge, and the Cochrane Controlled Trial Register from January 1997 to February 2013. Reference lists of the retrieved articles were reviewed to identify additional articles. Primary outcomes (postoperative pain scores, cosmetic score, and length of incision) and secondary outcomes (operating time, blood loss, conversion rates, postoperative complications, postoperative hospital stay, time to initial oral intake, and time to resume work) were pooled. Quantitative variables were calculated using the weighted mean difference (WMD), and qualitative variables were pooled using odds ratios (OR).

Results

25 appropriate RCTs were identified from 2128 published articles. 1841 patients were treated, 944 with SILC and 897 with CLC. SILC was superior to CLC in cosmetic score (WMD = 1.155, P<0.001), shorter length of incision (WMD = -3.285, P = 0.029), and postoperative pain within 12 h (VAS in 3-4 h, WMD = -0.704, P = 0.026; VAS in 6-8 h, WMD = -0.613, P = 0.010). CLC was superior to SILC in operating time (OT) (WMD = 13.613, P<0.001) and need of additional instruments (OR = 7.448, P<0.001). Other secondary outcomes were similar.

Conclusions

SILC offered a better cosmetic result and less postoperative pain for patients with uncomplicated cholelithiasis or polypoid lesions of the gallbladder. However, SILC was associated with a longer OT and required additional instruments.     

Hypertonic Saline for Brain Relaxation and Intracranial Pressure in Patients Undergoing Neurosurgical Procedures: A Meta-Analysis of Randomized Controlled Trials

Background

A wealth of evidence from randomized controlled trials (RCTs) has indicated that hypertonic saline (HS) is at least as effective as, if not better than, mannitol in the treatment of increased intracranial pressure(ICP). However, there is little known about the effects of HS in patients during neurosurgery. Thus, this meta-analysis was performed to compare the intraoperative effects of HS with mannitol in patients undergoing craniotomy.

Methods

According to the research strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries and conference proceedings were also searched. After literature searching, two investigators independently performed literature screening, quality assessment of the included trials and data extraction. The outcomes included intraoperative brain relaxation, intraoperative ICP, total volume of fluid required, diuresis, hemodynamic parameters, electrolyte level, mortality or dependence and adverse events.

Results

Seven RCTs with 468 participants were included. The quality of the included trials was acceptable. HS could significantly increase the odds of satisfactory intraoperative brain relaxation (OR: 2.25, 95% CI: 1.32–3.81; P = 0.003) and decrease the mean difference (MD) of maximal ICP (MD: −2.51mmHg, 95% CI: −3.39—1.93mmHg; P<0.00001) in comparison with mannitol with no significant heterogeneity among the study results. Compared with HS, mannitol had a more prominent diuretic effect. And patients treated with HS had significantly higher serum sodium than mannitol-treated patients.

Conclusions

Considering that robust outcome measures are absent because brain relaxation and ICP can be influenced by several factors except for the hyperosmotic agents, the results of present meta-analysis should be interpreted with cautions. Well-designed RCTs in the future are needed to further test the present results, identify the impact of HS on the clinically relevant outcomes and explore the potential mechanisms of HS.     

Endoscopic Vascular Harvest in Coronary Artery Bypass Grafting Surgery: A Meta-Analysis of Randomized Trials and Controlled Trials

OBJECTIVE:: This meta-analysis sought to determine whether endoscopic vascular graft harvesting (EVH) improves clinical and resource outcomes compared with conventional open graft harvesting (OVH) in adults undergoing coronary artery bypass surgery. METHODS:: A comprehensive search was undertaken to identify all randomized and nonrandomized trials of EVH versus OVH up to April 2005. The primary outcome was wound complications. Secondary outcomes included any other clinical morbidity and resource utilization. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences (SMD) and their 95% confidence intervals (95% CI) were analyzed. RESULTS:: Thirty-six trials of 9,632 patients undergoing saphenous vein harvest met the inclusion criteria (13 randomized; 23 nonrandomized). Risk of wound complications was significantly reduced by EVH compared with OVH (OR 0.31, 95% CI 0.23-0.41). Similarly, the risk of wound infections was significantly reduced (OR 0.23, 95% CI 0.20-0.53; P < 0.0001). Need for surgical wound intervention was also significantly reduced (OR 0.16, 95% CI 0.08-0.29). The incidence of pain, neuralgia, and patient satisfaction was improved with EVH compared with OVH. Postoperative myocardial infarction, stroke, reintervention for ischemia or angina recurrence, and mortality were not significantly different. Operative time was significantly increased (WMD 15.26 minutes; 95% CI 0.01, 30.51), hospital length of stay was reduced (WMD -0.85 days; 95% CI -1.55, -0.15), and readmissions were reduced (OR 0.53, 95% CI 0.29-0.98). Costs were insufficiently reported to allow for aggregate analysis. CONCLUSIONS:: Endoscopic vascular graft harvesting of the saphenous vein reduces wound complications and improves patient satisfaction and resource utilization. Further research is required to determine the incremental cost-effectiveness of EVH versus OVH.     

Intravenous N-Acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of Randomized,Controlled Trials

Background

Contrast-induced nephropathy (CIN) is one of the common causes of acute renal insufficiency after contrast procedures. Whether intravenous N-acetylcysteine (NAC) is beneficial for the prevention of contrast-induced nephropathy is uncertain. In this meta-analysis of randomized controlled trials, we aimed to assess the efficacy of intravenous NAC for preventing CIN after administration of intravenous contrast media.

Study Design

Relevant studies published up to September 2012 that investigated the efficacy of intravenous N-acetylcysteine for preventing CIN were collected from MEDLINE, OVID, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and the conference proceedings from major cardiology and nephrology meetings. The primary outcome was CIN. Secondary outcomes included renal failure requiring dialysis, mortality, and length of hospitalization. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Meta-regression analyses were also performed.

Results

Ten trials involving 1916 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-induced nephropathy was 0.68 (95% CI, 0.46 to 1.02), a nonsignificant trend towards benefit in patients treated with intravenous NAC. There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I² = 48%). Meta-regression revealed no significant relation between the relative risk of CIN and identified differences in participant or study characteristics.

Conclusion

This meta-analysis showed that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy. A large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for intravenous NAC in CIN prevention.     

Factors Affecting Blood Pressure Variability: Lessons Learned from Two Systematic Reviews of Randomized Controlled Trials

Systematic reviews can often reveal much more than the original objective of the work. The objectives of this retrospective analysis were to answer three basic questions about blood pressure variability: 1) Does blood pressure entry criterion have an effect on baseline blood pressure variability? 2) Do thiazide diuretics have a significant effect on blood pressure variability? and 3) Does systolic blood pressure vary to the same degree as diastolic blood pressure? This analysis of blood pressure variability is based on resting standardized research setting BP readings from two systematic reviews evaluating blood pressure lowering efficacy of thiazide diuretics from double blind randomized controlled trials in 33,611 patients with primary hypertension. The standard deviation reported in trials was the focus of the research and the unit of analysis. When a threshold systolic or diastolic blood pressure value is used to determine entry into a trial, baseline variability is significantly decreased, systolic from 14.0 to 9.3 mmHg and diastolic from 8.4 to 5.3 mmHg. Thiazides do not change BP variability as the standard deviation and coefficient of variation of systolic blood pressure and diastolic blood pressure did not differ between thiazide and placebo groups at end of treatment. The coefficient of variation of systolic blood pressure was significantly greater than the coefficient of variation of diastolic blood pressure. Entry criterion decreases the baseline blood pressure variability. Treatment with a thiazide diuretic does not affect blood pressure variability. Systolic blood pressure varies to a greater degree than diastolic blood pressure.