Colchicine for Secondary Prevention of Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

BackgroundReduction of inflammation with colchicine has emerged as a therapeutic option for secondary prevention of cardiovascular disease (CVD) in patients with coronary artery disease (CAD). Our objective was to consolidate evidence from randomized controlled trials (RCTs) evaluating the efficacy and safety of low-dose colchicine for secondary prevention of CVD among patients with CAD on standard medical therapy.MethodsRCTs comparing the incidence of cardiovascular (CV) events between patients with clinically manifest CAD randomized to colchicine vs placebo (or no colchicine) were included. The primary composite efficacy endpoint included CV mortality, myocardial infarction (MI), ischemic stroke, and urgent coronary revascularization. The DerSimonian and Laird random-effects model was used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsFour RCTs, with a pooled sample size of 11,594 patients, were included (colchicine n = 5774; placebo/no colchicine n = 5820). Included RCTs studied populations with stable CAD (N = 2) and acute coronary syndrome (N = 2). Compared with placebo or no colchicine, colchicine was associated with a statistically significant reduction in the incidence of the primary composite endpoint (pooled HR, 0.68; 95% CI, 0.54-0.81; I² = 37.7%). The reduction in CV events among patients randomized to colchicine was driven by statistically significant reductions in MIs, ischemic strokes, and urgent coronary revascularizations (P < 0.05 for all) and was relatively consistent among subgroups. The incidence of safety outcomes did not differ between groups (P > 0.05).ConclusionsIn secondary prevention of CV events, the addition of low-dose colchicine to standard medical therapy reduces the incidence of major CV events—except CV mortality—when compared with standard medical therapy alone.     

Laser Acupuncture for the Treatment of Asthma in Children: A Systematic Review of Randomized Controlled Trials

Background and objectives. Laser acupuncture has often been recommended as a treatment of asthma. The technique is noninvasive, and seems particularly suitable for children. However, the results from several clinical trials are contradictory. The objective of this review was to assess the effectiveness of laser acupuncture in the treatment of childhood asthma. Methods. Literature searches of electronic database were conducted in The Cochrane Library, Medline, EMBASE, AMED, CINAHL, and two Chinese literature databases (CNKI and VIP) up to February 2012. Randomized controlled trials (RCTs) testing laser acupuncture for asthma in children were included. No language restrictions were applied. Three authors independently selected articles, extracted data, and assessed trial quality. Results. Our searches identified 13 potential eligible studies, of which three with a total number of 176 patients met our inclusion criteria. The quality of included RCTs were low. One RCT with a parallel group design showed positive results, while two crossover RCTs generated negative results. There was variation in the type of patients, the interventions, and outcome measures. Because of the significant clinical and methodological heterogeneity, no meta-analysis was performed. Conclusions. The number of RCTs and their total sample sizes are small; and their methodological quality is low. Therefore, no compelling evidence exists to suggest that laser acupuncture is not an effective treatment for childhood asthma. Further rigorous studies are warranted.     

Yoga for Asthma? A Systematic Review of Randomized Clinical Trials

Objective. The objective of this systematic review was to assess the effectiveness of yoga as a treatment option for asthma. Method. Seven databases were searched from their inception to October 2010. Randomized clinical trials (RCTs) and non-randomized clinical trials (NRCTs) were considered, if they investigated any type of yoga in patients with asthma. The selection of studies, data extraction, and validation were performed independently by two reviewers. Results. Six RCTs and one NRCT met the inclusion criteria. Their methodological quality was mostly poor. Three RCTs and one NRCT suggested that yoga leads to a significantly greater reduction in spirometric measures, airway hyperresponsivity, dose of histamine needed to provoke a 20% reduction in forced expiratory volume in the first second, weekly number of asthma attacks, and need for drug treatment. Three RCTs showed no positive effects compared to various control interventions. Conclusions. The belief that yoga alleviates asthma is not supported by sound evidence. Further, more rigorous trials are warranted.     

Bupropion for Smoking Cessation in Patients Hospitalized With Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background

Smoking remains the most important modifiable risk factor for secondary prevention of cardiovascular events. We therefore performed a meta-analysis to determine the efficacy and safety of bupropion therapy started in-hospital for smoking cessation in patients with cardiovascular disease (CVD).

Methods

We systematically searched the medical literature to identify randomized controlled trials (RCTs) of in-hospital initiation of bupropion therapy for smoking cessation in patients with CVD. RCTs reporting smoking abstinence at 6 or 12 months were included.

Results

Three RCTs, including 773 patients, were included in our analyses. Participants were predominantly men (range of means, 69.0%-83.8%), and the majority were hospitalized with acute coronary syndrome (ACS) (range of means, 66%-100%). Treatment duration ranged from 8-12 weeks. At the end of treatment, bupropion was associated with a significant increase in point prevalence abstinence (relative risk [RR], 1.21; 95% confidence interval [CI], 1.02-1.45) but not continuous abstinence (RR, 1.19; 95% CI, 0.97-1.45). However, bupropion was not associated with a significant increase in point prevalence abstinence (RR, 1.17; 95% CI, 0.92-1.48) or continuous abstinence (RR, 1.16; 95% CI, 0.90-1.50) at 12 months. The results of the pooled analysis for major adverse cardiac and cerebrovascular events were inconclusive (RR, 1.28; 95% CI, 0.93-1.78).

Conclusions

We found that bupropion improved abstinence over placebo at the end of treatment but that this effect did not persist at 12 months. Because of inconsistent reporting of safety data, the safety profile of bupropion therapy in this patient population remains unclear.     

Duration of Dual Antiplatelet Therapy Following Drug-Eluting Stent Implantation: A Systematic Review and Meta-analysis of Randomized Controlled Trials

To evaluate the efficacy and safety of long-duration dual antiplatelet therapy (L-DAPT) compared to short-duration dual antiplatelet therapy (S-DAPT) after drug-eluting stent implantation. We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials assessing the clinical effect of L-DAPT vs S-DAPT after drug-eluting stent. Efficacy end points were all-cause mortality, cardiac mortality, myocardial infarction (MI), stent thrombosis (ST), and target vessel revascularization (TVR). Safety end points were TIMI major bleeding and stroke. Event rates were compared using a random-effects model. We identified 11 randomized controlled trials in which 33,520 patients were randomized to S-DAPT (N = 16,687) and L-DAPT (n = 16,833), respectively. Compared with L-DAPT, S-DAPT was associated with higher rate of MI and lower rate of TIMI major bleeding (1.40 [1.08-1.81] and 0.60 [0.41-0.89], respectively), without any significant differences in the rate of all-cause mortality, cardiac mortality, ST, TVR, and stroke (0.88 [0.75-1.04], 0.98 [0.79-1.22], 1.54 [0.95-2.50], 0.99 [0.73-1.34], and 1.01 [0.78-1.32], respectively). Our results showed that compared with L-DAPT, S-DAPT was associated with higher rate of MI and lower rate of major bleeding without any significant difference in the rates of all-cause mortality, cardiac mortality, ST, TVR, and stroke.     

Mavacamten Treatment for Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, yet pharmacological therapy has been unchanged for decades until the recent introduction of mavacamten, a first-in-class cardiac myosin inhibitor. We assessed the efficacy and safety of mavacamten in HCM. To date, only 3 randomized controlled trials (RCTs) compared the outcomes of mavacamten vs placebo for HCM. We used a fixed effects model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). The primary composite endpoint (PCE) was defined as either ≥1.5 mL/kg/min increase in peak oxygen consumption (pVO2) with ≥1 New York Heart Association functional class (NYHA-FC) improvement or ≥3.0 mL/kg/min increase in pVO2 without worsening of NYHA-FC. Secondary outcomes included ≥1 NYHA-FC improvement, septal reduction therapy (SRT) or guideline eligible for SRT, ≥1 serious adverse event (SAE), ≥1 treatment emergency adverse event (TEAE), atrial fibrillation (AF), and nonsustained ventricular tachycardia (NSVT). Three RCTs (n = 422, mean follow-up 24 weeks) were included. Compared to placebo, mavacamten achieved higher rates of PCE (RR 1.92; 95% CI 1.28-2.88; P = 0.002) and ≥1 NYHA-FC improvement (RR 2.10; 95% CI 1.66-2.67; P < 0.00001) and lower rates of SRT or guideline eligible for SRT (RR 0.29; 95% CI 0.22-0.39; P < 0.00001). There were no differences between both groups in ≥1 SAE, AF, and NSVT, however mavacamten had higher rates of ≥1 TEAE. In patients with HCM, mavacamten helps improve pVO2 and NYHA-FC and reduces SRT but may be associated with TEAE. Further research is warranted to evaluate the efficacy, safety, and long-term outcomes of mavacamten.     

The Effect of Computers for Weight Loss: A Systematic Review and Meta-analysis of Randomized Trials

BACKGROUND  

The use of computers to deliver education and support strategies has been shown to be effective in a variety of conditions. We conducted a systematic review and meta-analysis to evaluate the impact of computer-based technology on interventions for reducing weight.     

Quantifying the Impact of Algae Supplement on Blood Pressure: Systematic Review and Meta-analysis of Randomized Controlled Trials

The impact of Algae supplements and its extract on blood pressure has not concluded yet. The aim of this systematic review meta-analysis is to evaluate the antihypertensive activity of this group marine organism on human. Alga was used in some studies as capsules (from 500-mg to 8-g) and the follow-up duration changed from 17 days to 9 months. The difference in standardized mean and its corresponding 95% confidence interval (CI) was applied as the effect size of algae supplementation on systolic and diastolic blood pressure. Based on the results, a meta-analysis of 10 studies with baseline effect control demonstrated that there was no difference in the mean systolic blood pressure in the 2 groups SMD (95%CI): -1.05 (-2.85,0.76), but a significant difference in the mean diastolic blood pressure was observed and showed that the mean diastolic blood pressure in the treatment group was lower than the control group SMD(95%CI): -2.23 (-4.35,-0.11). A meta-analysis of 4 studies with no baseline control effect did not show significant results on both blood pressure. The evidence to support this systematic review meta-analysis requires more investigation and future large scale RCT clinical trial to confirm the results.     

Herbal Treatments of Asthma: A Systematic Review

Background: Asthma is a condition, often chronic, characterized by respiratory symptoms, variable airflow limitation and/or airway hyper-reactivity with symptoms causally related to family history, environmental influences, exposure to viruses and allergens as examples. The high economic burden associated with asthma is associated primarily with health care costs, missed work or school days. This systematic review was conducted to determine the study quality of articles investigating ayurvedic/collateral herbs, the effectiveness/efficacy and safety profile, as reported in the studies. Methods: Literature searches were conducted using PubMed, EMBASE, Mantis, Ovid, Annotated Bibliography of Indian Medicine, and Cochrane library to identify published trials on herbal medicines for asthma of which Ayruvedic herbals are a subset. Randomized Controlled Trials (RCTs) and Quasi-Experimental Designs (QEDs) were included in this systematic review. The classic Jadad Scale, Singh RCT Scale with additional domains than Jadad, Safety Scoring Scale for clinical trials and the Singh QED Scale based on expanded features of QEDs were used to assess study quality. Herbs included in Traditional Chinese Medicine were excluded from this review. Forty-two articles were retrieved and 37 studies were ultimately reviewed utilizing 3 independent evaluators/1 arbitrator. Results: Articles reviewed indicated benefit from most of the herbs used either as a primary or adjunctive treatment for Asthma. Study quality was mixed and therefore caution in interpretation of findings of usefulness of these herbals must be suggested. Limited safety information was mixed and generally was related to GI symptoms, though one herbal investigated reported more serious side effects. Conclusions: Herbs may be useful in treatment of asthma. There is insufficient evidence to make recommendations for or against the use of these herbals. Established effectiveness must be balanced with study quality and safety profile for the herb.     

Stem Cell Therapy for the Treatment of Nonischemic Cardiomyopathy: A Systematic Review of the Literature and Meta-analysis of Randomized Controlled Trials

Background

Stem cell (SC) therapy improves left ventricular function and dimensions in ischemic heart disease. Few small-scale trials have studied the effects of SC therapy on nonischemic cardiomyopathy (CMP), the leading cause of heart transplantation in the adults. The objectives were to gain a better insight into the effects of SC therapy for nonischemic CMP by conducting a systematic review of the literature and meta-analysis of randomized controlled trials.

Methods

Medline, EBM Reviews–Cochrane Central Register of Controlled Trials, Embase, and the ClinicalTrials.gov databases were screened for randomized controlled trials involving SC for treatment of nonischemic CMP. Weighted mean differences of improvement of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) were calculated using a random effect analysis model.

Results

Four trials were included in this meta-analysis (244 patients). The weighted mean LVEF improvement was 4.87% (95% confidence interval, 1.32-8.43%) in the treatment group compared with the control group (P = 0.01). The weighted mean decrease of LVEDD in the treatment group was of −2.19 mm (95% confidence interval, −5.69 to 1.30) compared with the control group (P = 0.22). On subgroup analysis, results were similar in studies involving peripheral CD34-positive or bone marrow-derived mononuclear cells (P = 0.33 for subgroup differences).

Conclusions

This is the first meta-analysis to show that for the treatment of nonischemic CMP, SC therapy might improve LVEF, but not LVEDD. Further trials should aim to circumscribe the optimal SC regimen in this setting, and to assess long-term clinical outcomes as primary end points.     

Clinical Decision Support Tools for Osteoporosis Disease Management: A Systematic Review of Randomized Controlled Trials

BACKGROUND  Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. OBJECTIVE  To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. DATA SOURCES  Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. REVIEW METHODS  Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. RESULTS  Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). CONCLUSION  Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

Selexipag in Patients With Pulmonary Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Despite the availability of treatments for all subgroups of pulmonary hypertension (PH), the prognosis for PH remains poor. This systematic review and meta-analysis aimed to determine the efficacy and safety of selexipag in patients with PH. A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with selexipag, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs). Selexipag was safe and significantly improved hospitalization for worsening of PH, WHO FC, mPAP, NT-proBNP, and cardiac index in patients with PH. Selexipag should be considered in patients with pulmonary arterial hypertension or chronic thromboembolic PH.     

Therapeutic Hypothermia and the Risk of Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Current guidelines recommend a period of moderate therapeutic hypothermia (TH) for comatose patients after cardiac arrest to improve clinical outcomes. However, in-vitro studies have reported platelet dysfunction, thrombocytopenia, and coagulopathy, results that might discourage clinicians from applying TH in clinical practice. We aimed to quantify the risks of hemorrhage observed in clinical studies.Medline and Embase were searched from inception to October 2015.Randomized controlled trials (RCTs) comparing patients undergoing TH with controls were selected, irrespective of the indications for TH. There were no restrictions for language, population, or publication year.Data on study characteristics, which included patients, details of intervention, and outcome measures, were extracted.Forty-three trials that included 7528 patients were identified from 2692 potentially relevant references. Any hemorrhage was designated as the primary outcome and was reported in 28 studies. The pooled results showed no significant increase in hemorrhage risk associated with TH (risk difference [RD] 0.005; 95% confidence interval [CI] −0.001–0.011; I², 0%). Among secondary outcomes, patients undergoing TH were found to have increased risk of thrombocytopenia (RD 0.109; 95% CI 0.038–0.179; I² 57.3%) and transfusion requirements (RD 0.021; 95% CI 0.003–0.040; I² 0%). The meta-regression analysis indicated that prolonged duration of cooling may be associated with increased risk of hemorrhage.TH was not associated with increased risk of hemorrhage despite the increased risk of thrombocytopenia and transfusion requirements. Clinicians should cautiously assess each patient''s risk-benefit profile before applying TH.     

Efficacy and Safety of E-Cigarette Use for Smoking Cessation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundPeople who smoke conventional cigarettes are increasingly turning to electronic cigarettes (e-cigarettes) as a pathway to quitting. However, the efficacy and safety of e-cigarettes for smoking cessation remains controversial.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), identified through a systematic search of the MEDLINE, EMBASE, and Cochrane CENTRAL databases. Inclusion was restricted to RCTs with a follow-up duration ≥6 months. The primary endpoint was the most rigorous criterion of biochemically validated abstinence at maximum follow-up, and the primary comparison was nicotine e-cigarettes versus any conventional (ie, non-e-cigarette) smoking cessation therapy. The Cochrane Risk of Bias Tool was used to assess bias. Count data were pooled across trials using random-effects models with inverse variance weighting to estimate relative risks (RRs) and corresponding 95% confidence intervals (CIs). We registered the study protocol with the Open Science Framework Registries (osf.io/26fkq).ResultsA total of 5 RCTs (n = 3253) were included. Compared with conventional smoking cessation therapies, the use of nicotine e-cigarettes was associated with an increase in abstinence, defined by the most rigorous criterion of abstinence reported (RR 1.77; 95% CI, 1.29-2.44). Nicotine e-cigarettes also increased abstinence (defined by the most rigorous criterion) compared with non-nicotine e-cigarettes (RR 1.56; 95% CI, 1.13-2.15). The incidence of death or serious adverse events was low across all trials at maximum follow-up.ConclusionsAmong individuals attempting to quit smoking, nicotine e-cigarettes are more efficacious than conventional nicotine replacement or behavioral smoking cessation therapies, and may prove beneficial in reducing smoking-related health risks.     

Strategies to Make Ramadan Fasting Safer in Type 2 Diabetics: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Observational Studies

Ramadan is the holy month for Muslims whereby they fast from predawn to after sunset and is observed by all healthy Muslim adults as well as a large population of type 2 diabetic Muslims.To determine the comparative effectiveness of various strategies that have been used for type 2 diabetic Muslim who fast during Ramadan.A systematic review and network meta-analysis of randomized controlled studies (RCT) as well as observational studies for patients with type 2 diabetes who fasted during Ramadan was conducted. Eight databases were searched from January 1980 through October 2015 for relevant studies. Two reviewers independently screened and assessed study for eligibility, assessed the risk of bias, and extracted relevant data. A network meta-analysis for each outcome was fitted separately, combining direct and indirect evidence for each comparison.Twenty-nine studies, 16 RCTs and 13 observational studies each met the inclusion criteria. The most common strategy used was drug changes during the Ramadan period, which found that the use of DPP-4 (Dipeptidyl peptidase inhibitor -4) inhibitors were associated with a reduction in incidence of experiencing hypoglycemia during Ramadan in both RCTs (pooled relative risk: 0.56; 95% confidence interval: 0.44–0.72) as well as in observational studies (pooled relative risk: 0.27; 0.09–0.75). Ramadan-focused education was shown to be beneficial in reducing hypoglycemia in observational studies but not RCTs (0.25 versus 1.00). Network meta-analyses suggest that incretin mimetics can reduce the risk of hypoglycemia by nearly 1.5 times.The newer antidiabetic agents appear to lower the risk of hypoglycemia and improved glycemic control when compared with sulfonylureas. Ramadan-focused education shows to be a promising strategy but more rigorous examination from RCTs are required.