Niacin for primary and secondary prevention of cardiovascular events.

BACKGROUND: Nicotinic acid (niacin) is known to decrease LDL-cholesterol, and triglycerides, and increase HDL-cholesterol levels. The evidence of benefits with niacin monotherapy or add-on to statin-based therapy is controversial. OBJECTIVES: To assess the effectiveness of niacin therapy versus placebo, administered as monotherapy or add-on to statin-based therapy in people with or at risk of cardiovascular disease (CVD) in terms of mortality, CVD events, and side effects. SEARCH METHODS: Two reviewers independently and in duplicate screened records and potentially eligible full texts identified through electronic searches of CENTRAL, MEDLINE, Embase, Web of Science, two trial registries, and reference lists of relevant articles (latest search in August 2016). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that either compared niacin monotherapy to placebo/usual care or niacin in combination with other component versus other component alone. We considered RCTs that administered niacin for at least six months, reported a clinical outcome, and included adults with or without established CVD. DATA COLLECTION AND ANALYSIS: Two reviewers used pre-piloted forms to independently and in duplicate extract trials characteristics, risk of bias items, and outcomes data. Disagreements were resolved by consensus or third party arbitration. We conducted random-effects meta-analyses, sensitivity analyses based on risk of bias and different assumptions for missing data, and used meta-regression analyses to investigate potential relationships between treatment effects and duration of treatment, proportion of participants with established coronary heart disease and proportion of participants receiving background statin therapy. We used GRADE to assess the quality of evidence. MAIN RESULTS: We included 23 RCTs that were published between 1968 and 2015 and included 39,195 participants in total. The mean age ranged from 33 to 71 years. The median duration of treatment was 11.5 months, and the median dose of niacin was 2 g/day. The proportion of participants with prior myocardial infarction ranged from 0% (4 trials) to 100% (2 trials, median proportion 48%); the proportion of participants taking statin ranged from 0% (4 trials) to 100% (12 trials, median proportion 100%).Using available cases, niacin did not reduce overall mortality (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.97 to 1.12; participants = 35,543; studies = 12; I2 = 0%; high-quality evidence), cardiovascular mortality (RR 1.02, 95% CI 0.93 to 1.12; participants = 32,966; studies = 5; I2 = 0%; moderate-quality evidence), non-cardiovascular mortality (RR 1.12, 95% CI 0.98 to 1.28; participants = 32,966; studies = 5; I2 = 0%; high-quality evidence), the number of fatal or non-fatal myocardial infarctions (RR 0.93, 95% CI 0.87 to 1.00; participants = 34,829; studies = 9; I2 = 0%; moderate-quality evidence), nor the number of fatal or non-fatal strokes (RR 0.95, 95% CI 0.74 to 1.22; participants = 33,661; studies = 7; I2 = 42%; low-quality evidence). Participants randomised to niacin were more likely to discontinue treatment due to side effects than participants randomised to control group (RR 2.17, 95% CI 1.70 to 2.77; participants = 33,539; studies = 17; I2 = 77%; moderate-quality evidence). The results were robust to sensitivity analyses using different assumptions for missing data. AUTHORS' CONCLUSIONS: Moderate- to high-quality evidence suggests that niacin does not reduce mortality, cardiovascular mortality, non-cardiovascular mortality, the number of fatal or non-fatal myocardial infarctions, nor the number of fatal or non-fatal strokes but is associated with side effects. Benefits from niacin therapy in the prevention of cardiovascular disease events are unlikely.

Fibrates for primary prevention of cardiovascular disease events.

BACKGROUND: Fibrates are effective for modifying atherogenic dyslipidaemia, and particularly for lowering serum triglycerides. However, evidence that fibrates reduce mortality and morbidity associated with cardiovascular disease (CVD), or overall mortality and morbidity, in the primary prevention of CVD is lacking. OBJECTIVES: This Cochrane Review and meta-analysis aimed to evaluate the clinical benefits and harms of fibrates versus placebo or usual care or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone for the primary prevention of cardiovascular disease (CVD) morbidity and mortality. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and Web of Science (all from inception to 19 May 2016). We searched four clinical trial registers (last searched on 3 August 2016) with the help of an experienced professional librarian. We searched the databases to identify randomised controlled trials (RCTs) evaluating the clinical effects of fibrate therapy in the primary prevention of CVD events. We did not impose any language restrictions. SELECTION CRITERIA: We aimed to include all RCTs comparing the effects of fibrate monotherapy versus placebo or usual care, or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone. Included studies had a follow-up of at least six months for the primary prevention of CVD events. We excluded trials with clofibrate, because it was withdrawn from the market in 2002. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for potential study inclusion. Two review authors independently retrieved the full-text papers and extracted data. Disagreements were resolved by consensus. We calculated risk ratios (RRs) and accompanying 95% confidence intervals (CIs) for aggregate data on primary and secondary outcomes. We tested for heterogeneity with the Cochrane Q-test and used the I2 statistic to measure inconsistency of treatment effects across studies. Using the GRADE approach, we assessed the quality of the evidence and used the GRADE profiler software (GRADEpro GDT) to import data from Review Manager 5 to create 'Summary of findings' tables. MAIN RESULTS: We identified six eligible trials including 16,135 individuals. The mean age of trial populations varied across trials; between 47.3 and 62.3 years. Four trials included individuals with diabetes mellitus type 2 only. The mean treatment duration and follow-up of participants across trials was 4.8 years. We judged the risks of selection and performance bias to be low; risks of detection bias, attrition bias, and reporting bias were unclear. Reporting of adverse effects by included trials was very limited; that is why we used discontinuation of therapy due to adverse effects as a proxy for adverse effects. Patients treated with fibrates had a reduced risk for the combined primary outcome of CVD death, non-fatal myocardial infarction, or non-fatal stroke compared to patients on placebo (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74 to 0.96; participants = 16,135; studies = 6; moderate-quality of evidence). For secondary outcomes we found RRs for fibrate therapy compared with placebo of 0.79 for combined coronary heart disease death or non-fatal myocardial infarction (95% CI 0.68 to 0.92; participants = 16,135; studies = 6; moderate-quality of evidence); 1.01 for overall mortality (95% CI 0.81 to 1.26; participants = 8471; studies = 5; low-quality of evidence); 1.01 for non-CVD mortality (95% CI 0.76 to 1.35; participants = 8471; studies = 5; low-quality of evidence); and 1.38 for discontinuation of therapy due to adverse effects (95% CI 0.71 to 2.68; participants = 4805; studies = 3; I2 = 74%; very low-quality of evidence). Data on quality of life were not available from any trial. Trials that evaluated fibrates in the background of statins (2 studies) showed no benefits in preventing cardiovascular events. AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests that fibrates lower the risk for cardiovascular and coronary events in primary prevention, but the absolute treatment effects in the primary prevention setting are modest (absolute risk reductions < 1%). There is low-quality evidence that fibrates have no effect on overall or non-CVD mortality. Very low-quality evidence suggests that fibrates are not associated with increased risk for adverse effects.

Colchicine for prevention of cardiovascular events.

BACKGROUND: Colchicine is an anti-inflammatory drug that is used for a wide range of inflammatory diseases. Cardiovascular disease also has an inflammatory component but the effects of colchicine on cardiovascular outcomes remain unclear. Previous safety analyses were restricted to specific patient populations. OBJECTIVES: To evaluate potential cardiovascular benefits and harms of a continuous long-term treatment with colchicine in any population, and specifically in people with high cardiovascular risk. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry, citations of key papers, and study references in January 2015. We also contacted investigators to gain unpublished data. SELECTION CRITERIA: Randomised controlled trials (parallel-group or cluster design or first phases of cross-over studies) comparing colchicine over at least six months versus any control in any adult population. DATA COLLECTION AND ANALYSIS: Primary outcomes were all-cause mortality, myocardial infarction, and adverse events. Secondary outcomes were cardiovascular mortality, stroke, heart failure, non-scheduled hospitalisations, and non-scheduled cardiovascular interventions. We conducted predefined subgroup analyses, in particular for participants with high cardiovascular risk. . MAIN RESULTS: We included 39 randomised parallel-group trials with 4992 participants. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; participants = 4174; studies = 30; I² = 27%; moderate quality of evidence). There is uncertainty surrounding the effect of colchicine in reducing cardiovascular mortality (RR 0.34, 95% CI 0.09 to 1.21, I² = 9%; participants = 1132; studies = 7; moderate quality of evidence). Colchicine reduced the risk for total myocardial infarction (RR 0.20, 95% CI 0.07 to 0.57; participants = 652; studies = 2; moderate quality of evidence). There was no effect on total adverse events (RR 1.52, 95% CI 0.93 to 2.46; participants = 1313; studies = 11; I² = 45%; very low quality of evidence) but gastrointestinal intolerance was increased (RR 1.83, 95% CI 1.03 to 3.26; participants = 1258; studies = 11; I² = 74%; low quality of evidence). Colchicine showed no effect on heart failure (RR 0.62, 95% CI 0.10 to 3.88; participants = 462; studies = 3; I² = 45%; low quality of evidence) and no effect on stroke (RR 0.38, 95% CI 0.09 to 1.70; participants = 874; studies = 3; I² = 45%; low quality of evidence). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects on other outcomes were very uncertain. Summary effects of RCTs specifically focusing on participants with high cardiovascular risk were similar (4 trials; 1230 participants). AUTHORS' CONCLUSIONS: There is much uncertainty surrounding the benefits and harms of colchicine treatment. Colchicine may have substantial benefits in reducing myocardial infarction in selected high-risk populations but uncertainty about the size of the effect on survival and other cardiovascular outcomes is high, especially in the general population from which most of the studies in our review were drawn. Colchicine is associated with gastrointestinal side effects based on low-quality evidence. More evidence from large-scale randomised trials is needed.

Statins for acute coronary syndrome.

BACKGROUND: The early period following the onset of acute coronary syndrome (ACS) represents a critical stage of coronary heart disease, with a high risk of recurrent events and deaths. The short-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from ACS are unclear. This is an update of a review previously published in 2011. OBJECTIVES: To assess the effects, both harms and benefits, of early administered statins in patients with ACS, in terms of mortality and cardiovascular events. SEARCH METHODS: We updated the searches of CENTRAL (2013, Issue 3), MEDLINE (Ovid) (1946 to April Week 1 2013), EMBASE (Ovid) (1947 to 2013 Week 14), and CINAHL (EBSCO) (1938 to 2013) on 12 April 2013. We applied no language restrictions. We supplemented the search by contacting experts in the field, by reviewing the reference lists of reviews and editorials on the topic, and by searching trial registries. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing statins with placebo or usual care, with initiation of statin therapy within 14 days following the onset of ACS, follow-up of at least 30 days, and reporting at least one clinical outcome. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias and extracted data. We calculated risk ratios (RRs) for all outcomes in the treatment and control groups and pooled data using random-effects models. MAIN RESULTS: Eighteen studies (14,303 patients) compared early statin treatment versus placebo or no treatment in patients with ACS. The new search did not identify any new studies for inclusion. There were some concerns about risk of bias and imprecision of summary estimates. Based on moderate quality evidence, early statin therapy did not decrease the combined primary outcome of death, non-fatal myocardial infarction, and stroke at one month (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08) or four months (RR 0.93, 95% CI 0.81 to 1.06) of follow-up when compared to placebo or no treatment. There were no statistically significant risk reductions from statins for total death, total myocardial infarction, total stroke, cardiovascular death, revascularization procedures, and acute heart failure at one month or at four months, although there were favorable trends related to statin use for each of these endpoints. Moderate quality evidence suggests that the incidence of unstable angina was significantly reduced at four months following ACS (RR 0.76, 95% CI 0.59 to 0.96). There were nine individuals with myopathy (elevated creatinine kinase levels more than 10 times the upper limit of normal) in statin-treated patients (0.13%) versus one (0.015%) in the control groups. Serious muscle toxicity was mostly limited to patients treated with simvastatin 80 mg. AUTHORS' CONCLUSIONS: Based on moderate quality evidence, due to concerns about risk of bias and imprecision, initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months, but reduces the occurrence of unstable angina at four months following ACS. Serious side effects were rare.

Fibrates for primary prevention of cardiovascular disease events.

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the clinical benefit and harm of fibrates versus placebo or usual care or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone for the primary prevention of CVD events and mortality.

Statins for acute coronary syndrome.

BACKGROUND: The early period following the onset of acute coronary syndromes (ACS) represents a critical stage of coronary heart disease with a high risk for recurrent events and deaths. The short-term effects of early treatment with statins in patients suffering from ACS on patient-relevant outcomes are unclear. OBJECTIVES: To assess the benefits and harms of early administered statins in patients with ACS from randomized controlled trials (RCTs). SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL (to 1 February 2010). No language restrictions were applied. We supplemented the search by contacting experts in the field, by reviewing reference lists of reviews and editorials on the topic, and by searching trial registries. SELECTION CRITERIA: RCTs comparing statins with placebo or usual care, initiation of statin therapy within 14 days following the onset of ACS, and follow-up of at least 30 days reporting at least one clinical outcome. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. We pooled treatment effects and calculated risk ratios (RRs) for all outcomes in the treatment and control groups using a random effects model. MAIN RESULTS: Eighteen studies (14,303 patients) compared early statin treatment versus placebo or usual care in patients with ACS. Compared to placebo or usual care, early statin therapy did not decrease the combined primary outcome of death, non-fatal myocardial infarction (MI), and stroke at one month (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08) and four months (RR 0.93, 95% CI 0.81 to 1.06) of follow-up. There were no statistically significant risk reductions from statins for total death, total MI, total stroke, cardiovascular death, revascularization procedures, and acute heart failure at one month and at four months, although there were favorable trends related to statin use for each of these endpoints. The incidence of episodes of unstable angina was significantly reduced at four months following ACS (RR 0.76, 95% CI 0.59 to 0.96). There were nine individuals with myopathy (elevated creatinine kinase levels > 10 times the upper limit of normal) in statin treated patients (0.13%) versus one (0.015%) in the control groups. Serious muscle toxicity was mostly limited to patients treated with simvastatin 80 mg. AUTHORS' CONCLUSIONS: Based on available evidence, initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months, but reduces the occurrence of unstable angina at four months following ACS.

Randomisation to protect against selection bias in healthcare trials.

BACKGROUND: Randomised trials use the play of chance to assign participants to comparison groups. The unpredictability of the process, if not subverted, should prevent systematic differences between comparison groups (selection bias). Differences due to chance will still occur and these are minimised by randomising a sufficiently large number of people. OBJECTIVES: To assess the effects of randomisation and concealment of allocation on the results of healthcare studies. SEARCH STRATEGY: We searched the Cochrane Methodology Register, MEDLINE, SciSearch and reference lists up to September 2009. In addition, we screened articles citing included studies (ISI Science Citation Index) and papers related to included studies (PubMed). SELECTION CRITERIA: Eligible study designs were cohorts of studies, systematic reviews or meta-analyses of healthcare interventions that compared random allocation versus non-random allocation or adequate versus inadequate/unclear concealment of allocation in randomised trials. Outcomes of interest were the magnitude and direction of estimates of effect and imbalances in prognostic factors. DATA COLLECTION AND ANALYSIS: We retrieved and assessed studies that appeared to meet the inclusion criteria independently. At least two review authors independently appraised methodological quality and extracted information. We prepared tabular summaries of the results for each comparison and assessed the results across studies qualitatively to identify common trends or discrepancies. MAIN RESULTS: A total of 18 studies (systematic reviews or meta-analyses) met our inclusion criteria. Ten compared random allocation versus non-random allocation and nine compared adequate versus inadequate or unclear concealment of allocation within controlled trials. All studies were at high risk of bias.For the comparison of randomised versus non-randomised studies, four comparisons yielded inconclusive results (differed between outcomes or different modes of analysis); three comparisons showed similar results for random and non-random allocation; two comparisons had larger estimates of effect in non-randomised studies than in randomised trials; and two comparisons had larger estimates of effect in randomised than in non-randomised studies.Five studies found larger estimates of effect in trials with inadequate concealment of allocation than in trials with adequate concealment. The four other studies did not find statistically significant differences. AUTHORS' CONCLUSIONS: The results of randomised and non-randomised studies sometimes differed. In some instances non-randomised studies yielded larger estimates of effect and in other instances randomised trials yielded larger estimates of effect. The results of controlled trials with adequate and inadequate/unclear concealment of allocation sometimes differed. When differences occurred, most often trials with inadequate or unclear allocation concealment yielded larger estimates of effects relative to controlled trials with adequate allocation concealment. However, it is not generally possible to predict the magnitude, or even the direction, of possible selection biases and consequent distortions of treatment effects from studies with non-random allocation or controlled trials with inadequate or unclear allocation concealment.

Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis.

CONTEXT: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. OBJECTIVE: To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect. DATA SOURCES: Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008. STUDY SELECTION: Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs. DATA EXTRACTION: Reviewers with methodological expertise conducted data extraction independently. RESULTS: The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit. CONCLUSIONS: Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.

Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis.

BACKGROUND: Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents. METHODS: We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. FINDINGS: Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel-eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66-0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel-eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021). INTERPRETATION: The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents.

Accuracy of drug advertisements in medical journals under new law regulating the marketing of pharmaceutical products in Switzerland.

BACKGROUND: New legal regulations for the marketing of pharmaceutical products were introduced in 2002 in Switzerland. We investigated whether claims in drug advertisements citing published scientific studies were justified by these studies after the introduction of these new regulations. METHODS: In this cross-sectional study, two independent reviewers screened all issues of six major Swiss medical journals published in the year 2005 to identify all drug advertisements for analgesic, gastrointestinal and psychopharmacologic drugs and evaluated all drug advertisements referring to at least one publication. The pharmaceutical claim was rated as being supported, being based on a potentially biased study or not to be supported by the cited study according to pre-specified criteria. We also explored factors likely to be associated with supported advertisement claims. RESULTS: Of 2068 advertisements 577 (28%) promoted analgesic, psychopharmacologic or gastrointestinal drugs. Among them were 323 (56%) advertisements citing at least one reference. After excluding multiple publications of the same drug advertisement and advertisements with non-informative references, there remained 29 unique advertisements with at least one reference to a scientific study. These 29 advertisements contained 78 distinct pairs of claims of analgesic, gastrointestinal and psychopharmacologic drugs and referenced studies. Thirty-seven (47%) claims were supported, 16 (21%) claims were not supported by the corresponding reference, and 25 (32%) claims were based on potentially biased evidence, with no relevant differences between drug groups. Studies with conflict of interest and studies stating industry funding were more likely to support the corresponding claim (RR 1.52, 95% CI 1.07-2.17 and RR 1.50, 95% CI 0.98-2.28) than studies without identified conflict of interest and studies without information on type of funding. CONCLUSION: Following the introduction of new regulations for drug advertisement in Switzerland, 53% of all assessed pharmaceutical claims published in major medical journals are not supported by the cited referenced studies or based on potentially biased study information. In light of the discrepancy between the new legislation and the endorsement of these regulations, physicians should not trust drug advertisement claims even when they seem to refer to scientific studies.

Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials.

BACKGROUND: Low-carbohydrate diets have become increasingly popular for weight loss. However, evidence from individual trials about benefits and risks of these diets to achieve weight loss and modify cardiovascular risk factors is preliminary. METHODS: We used the Cochrane Collaboration search strategy to identify trials comparing the effects of low-carbohydrate diets without restriction of energy intake vs low-fat diets in individuals with a body mass index (calculated as weight in kilograms divided by the square of height in meters) of at least 25. Included trials had to report changes in body weight in intention-to-treat analysis and to have a follow-up of at least 6 months. Two reviewers independently assessed trial eligibility and quality of randomized controlled trials. RESULTS: Five trials including a total of 447 individuals fulfilled our inclusion criteria. After 6 months, individuals assigned to low-carbohydrate diets had lost more weight than individuals randomized to low-fat diets (weighted mean difference, -3.3 kg; 95% confidence interval [CI], -5.3 to -1.4 kg). This difference was no longer obvious after 12 months (weighted mean difference, -1.0 kg; 95% CI, -3.5 to 1.5 kg). There were no differences in blood pressure. Triglyceride and high-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-carbohydrate diets (after 6 months, for triglycerides, weighted mean difference, -22.1 mg/dL [-0.25 mmol/L]; 95% CI, -38.1 to -5.3 mg/dL [-0.43 to -0.06 mmol/L]; and for high-density lipoprotein cholesterol, weighted mean difference, 4.6 mg/dL [0.12 mmol/L]; 95% CI, 1.5-8.1 mg/dL [0.04-0.21 mmol/L]), but total cholesterol and low-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-fat diets (weighted mean difference in low-density lipoprotein cholesterol after 6 months, 5.4 mg/dL [0.14 mmol/L]; 95% CI, 1.2-10.1 mg/dL [0.03-0.26 mmol/L]). CONCLUSIONS: Low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered.

Effects of early treatment with statins on short-term clinical outcomes in acute coronary syndromes: a meta-analysis of randomized controlled trials.

CONTEXT: The short-term effects of early treatment with statins in patients after the onset of acute coronary syndromes (ACS) for the outcomes of death, myocardial infarction (MI), and stroke are unclear. OBJECTIVE: To evaluate relevant outcomes of patients from randomized controlled trials comparing early statin therapy with placebo or usual care at 1 and 4 months following ACS. DATA SOURCES AND STUDY SELECTION: Systematic search of electronic databases (MEDLINE, EMBASE, PASCAL, Cochrane Central Register) from their inception to August 2005, which was supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of randomized controlled trials that compared treatment with statins with a control, were initiated within 14 days after onset of ACS, and had a minimal follow-up of 30 days. Trials with cerivastatin were only included in a sensitivity analysis. DATA EXTRACTION: Information on baseline characteristics of included trials and patients, reported methodological quality, lipid levels, and clinical outcome was independently extracted by 2 investigators. Investigators from each included trial contributed additional data if necessary. DATA SYNTHESIS: Twelve trials involving 13 024 patients with ACS were included in the meta-analysis. The risk ratios for the combined end point of death, MI, and stroke for patients treated with early statin therapy compared with control therapy were 0.93 (95% confidence interval [CI], 0.80-1.09; P = .39) at 1 month and 0.93 (95% CI, 0.81-1.07; P = .30) at 4 months following ACS. There were no statistically significant risk reductions from statins for total death, total MI, total stroke, cardiovascular death, fatal or nonfatal MI, or revascularization procedures (percutaneous coronary intervention or coronary artery bypass graft surgery). Sensitivity analyses with restriction to trials of high quality or with additional data from a large trial using cerivastatin indicated summary risk ratios even closer to 1. CONCLUSION: Based on available evidence, initiation of statin therapy within 14 days following onset of ACS does not reduce death, MI, or stroke up to 4 months.

Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis.

Colchicine is an old anti-inflammatory drug that has shown substantial cardiovascular benefits in recent trials. We systematically reviewed cardiovascular benefits and harms of colchicine in any population and specifically in patients with high cardiovascular risk. We evaluated randomised controlled trials comparing colchicine over at least 6 months versus any control in any adult population. Primary outcomes were all-cause mortality, myocardial infarction and adverse events. Cardiovascular mortality was a secondary outcome. We included 39 trials with 4992 patients. The quality of evidence for mortality outcomes and myocardial infarction was moderate but lower for adverse events. Colchicine had no effect on all-cause mortality (RR 0.94, 95% CI 0.82 to 1.09; I(2)=27%; 30 trials). Cardiovascular mortality was reduced in some but not all meta-analytical models (random-effects RR 0.34, 0.09 to 1.21, I(2)=9%; Peto's OR 0.24, 0.09 to 0.64, I(2)=15%; Mantel-Haenszel fixed-effect RR 0.20, 0.06 to 0.68, I(2)=0%; 7 trials). The risk for myocardial infarction was reduced (RR 0.20, 0.07 to 0.57; 2 trials). There was no effect on total adverse events (RR 1.52, 0.93 to 2.46, I(2)=45%; 11 trials) but gastrointestinal intolerance was increased (RR 1.83, 1.03 to 3.26, I(2)=74%; 11 trials). Reporting of serious adverse events was inconsistent; no event occurred over 824 patient-years (4 trials). Effects in high cardiovascular risk populations were similar (4 trials; 1230 patients). We found no evidence supporting colchicine doses above 1 mg/day. Colchicine may have substantial cardiovascular benefits; however, there is sufficient uncertainty about its benefit and harm to indicate the need for large-scale trials to further evaluate this inexpensive, promising treatment in cardiovascular disease.

A systematic review and metaanalysis on the effects of garlic preparations on blood pressure in individuals with hypertension.

BACKGROUND: Many patients prefer herbal medications to conventional drugs. Limited trial evidence suggests that garlic preparations reduce high blood pressure (BP). METHODS: We searched electronic databases through March 2014 to identify all randomized controlled trials that compared a garlic preparation to placebo in hypertensive patients. Trials were required to report BP values at baseline and after a follow-up of at least 4 weeks. RESULTS: Nine double-blind trials with 482 individuals fulfilled our inclusion criteria. Included trials were rather small, and the quality of the majority of included trials was moderate. Follow-up ranged from 8 to 26 weeks. All trials reported office BP measurements. Systolic BP and diastolic BP (SBP and DBP) were more effectively reduced in individuals treated with garlic preparations than in individuals treated with placebo. However, heterogeneity was high (weighted mean difference (WMD) for SBP was -9.1 mm Hg; 95% confidence interval (CI), -12.7 to -5.4; P for heterogeneity = 0.0006; and I2 = 71%; WMD for BP was -3.8 mm Hg; 95% CI, -6.7 to -1.0; P for heterogeneity = 0.00001; I2 = 80%). When analyses were restricted to higher-quality trials using intention-to-treat analysis or to trials with concealed treatment allocation and standardized and blinded BP measurement, effect sizes for SBP but not for DBP were lower and heterogeneity disappeared. CONCLUSIONS: Although evidence from this review suggests that garlic preparations may lower BP in hypertensive individuals, the evidence is not strong. A well-conducted and powered trial of longer duration is needed to confirm these findings.

Balloon angioplasty or medical therapy for hypertensive patients with atherosclerotic renal artery stenosis? A meta-analysis of randomized controlled trials.

PURPOSE: The optimal treatment for hypertensive patients with atherosclerotic renal artery stenosis is controversial. We performed a meta-analysis comparing the effects of balloon angioplasty and medical therapy in these patients. METHODS: We searched MEDLINE, EMBASE, the Science Citation Index, the Cochrane Controlled Trials Registry, and reference lists. Authors of published trials were contacted. RESULTS: We identified three trials involving a total of 210 patients with moderate-to-severe (> or = 50%) unilateral or bilateral atherosclerotic renal artery stenosis and poorly controlled hypertension who were followed for at least 3 months after intervention. Balloon angioplasty was significantly more effective in reducing blood pressure than was medical therapy; the weighted mean difference between the two treatments was -7 mm Hg (95% confidence interval [CI]: -12 to -1 mm Hg) for systolic blood pressure and -3 mm Hg (95% CI: -6 to -1 mm Hg) for diastolic blood pressure. There was no consistent difference in changes in renal function. Patients treated with balloon angioplasty were more likely to have patent renal arteries after 12 months (52% vs. 19%; odds ratio [OR] = 4.2; 95% CI: 1.8 to 9.8), used fewer antihypertensive medications, and appeared to have fewer major cardiovascular and renovascular complications (OR = 0.27; 95% CI: 0.06 to 1.23; P = 0.09). CONCLUSION: Balloon angioplasty has a modest but significant effect on blood pressure and should be considered for patients with atherosclerotic renal artery stenosis and poorly controlled hypertension. There is no evidence supporting its use in improving or preserving renal function, although none of the trials were designed to address this issue.

Clinical outcomes of primary stenting versus balloon angioplasty in patients with myocardial infarction: a meta-analysis of randomized controlled trials.

PURPOSE: To examine whether primary stenting as compared with primary balloon angioplasty reduces clinical outcomes in patients with myocardial infarction. METHODS: Major medical databases from 1979 to March 2002 were searched for randomized controlled trials that compared primary stenting with balloon angioplasty in patients with myocardial infarction. Two independent reviewers selected and extracted data from identified trials. The outcomes were mortality at 30 days, 6 months, and 12 months; recurrent events; and bleeding. RESULTS: Nine trials with a total of 4433 patients fulfilled the inclusion criteria. The odds ratios for mortality after stenting as compared with balloon angioplasty were 1.17 (95% confidence interval [CI]: 0.78 to 1.74) at 30 days, 1.07 (95% CI: 0.76 to 1.52) at 6 months, and 1.09 (95% CI: 0.80 to 1.50) at 12 months (P for heterogeneity >0.1 for each comparison). The odds ratios for reinfarction after stenting as compared with balloon angioplasty were 0.52 (95% CI: 0.31 to 0.87) at 30 days, 0.67 (95% CI: 0.45 to 1.00) at 6 months, and 0.67 (95% CI: 0.45 to 0.99) at 12 months; for target vessel revascularization, they were 0.46 (95% CI: 0.34 to 0.61) at 30 days, 0.42 (95% CI: 0.35 to 0.51) at 6 months, and 0.48 (95% CI: 0.39 to 0.59) at 12 months (P for heterogeneity >0.1 for all estimates with the exception of reinfarction at 12 months where P=0.08). The odds ratio for postinterventional bleeding complications after stenting as compared with balloon angioplasty was 1.34 (95% CI: 0.95 to 1.88; P for heterogeneity >0.1). CONCLUSION: Compared with balloon angioplasty, primary stenting is not associated with lower mortality, but is associated with a lower risk of reinfarction and target vessel revascularization.

The cost effectiveness of ACE inhibitors as first-line antihypertensive therapy.

BACKGROUND: Current hypertension guidelines differ in their recommendations for first-line antihypertensive therapy. OBJECTIVE: To evaluate the cost effectiveness of ACE inhibitor therapy as antihypertensive first-line therapy as compared with conventional antihypertensive therapy with beta-adrenoceptor antagonists or diuretics. STUDY DESIGN: Cost-effectiveness analysis based on data from randomised trials and observational studies comparing the effectiveness of ACE inhibitor and conventional antihypertensive therapy, we constructed a Markov model to compare four strategies in the management of uncomplicated hypertension: (i) prescribing ACE inhibitor therapy to all patients; (ii) prescribing conventional therapy to all patients; (iii) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on electrocardiography (ECG); or (iv) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on echocardiography. METHODS: Cost data were derived from the medical literature and focus groups, and utility values were derived from patients on antihypertensive monotherapy. All costs were calculated in 1999 Canadian dollars, but are reported in US dollars according to the 1999 purchasing power parity rate for medical and healthcare. The effectiveness of ACE inhibitor therapy in the presence of left ventricular hypertrophy was derived from observational studies. The time horizon was over a lifetime. PERSPECTIVE: Third-party payer. PATIENTS/PARTICIPANTS: A cohort of men aged 40 years without cardiovascular comorbidity requiring antihypertensive drug therapy. MAIN OUTCOME MEASURES AND RESULTS: In the baseline analysis, all four strategies resulted in expected discounted QALYs that differed from each other only at the third decimal point (i.e. less than 0.003). Given the uncertainties in the variable estimates and the small size of the differences, these differences are extremely small and unlikely to represent real differences. Even accepting the small gains as real, the resulting cost-effectiveness ratios are unattractively high: $US 200,000 per QALY gained for the echocardiography strategy (compared with ECG), and $US 700,000 for the "ACE inhibitor for all" strategy (compared with ECG). The incremental cost effectiveness of prescribing ACE inhibitor therapy to everybody was never less than $US 100,000/QALY in the sensitivity analysis. CONCLUSIONS: Prescribing ACE inhibitors as antihypertensive first-line therapy in patients without cardiovascular morbidity cannot be recommended at the present time unless the acquisition costs of ACE inhibitors become substantially more attractive.

Assessing work ability--a cross-sectional study of interrater agreement between disability claimants, treating physicians, and medical experts.

OBJECTIVES: It is unclear to what extent assessments of work ability differ between disability claimants, their treating physicians, and multidisciplinary medical expert teams. METHODS: We compared assessments of work ability for consecutive disability claimants referred to a multidisciplinary assessment center in Switzerland over a 4-year period. Assessments were made for the last job (LJ) prior to claiming a disability benefit and an alternative job (AJ) thought to suit the claimant's physical and mental abilities. Mean differences (MD) in percentage work ability between assessments from claimants, physicians, and experts were then estimated in a linear regression model. RESULTS: The 3562 claims made during the study period were mostly due to musculoskeletal and depressive disorders. Assessments differed little between claimants and physicians [LJ MD 1.3% (95% confidence interval [95% CI] 0.5-2.2%); AJ MD 11% (95% CI 10-12%)]. Experts on average assessed a claimant's work ability higher than either the claimant or physician, particularly in the AJ [MD between expert and claimant 57% (95% CI 56-58%) and between expert and physician 46% (95% CI 45-48%)]. CONCLUSIONS: Assessments of work ability differed substantially between experts in multidisciplinary medical teams and both claimants and their treating physicians. A careful evaluation of the disability assessment process is needed in an effort to reduce disagreement between expert teams and treating physicians and so improve acceptance of the process.

Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To quantify the overall effects of bariatric surgery compared with non-surgical treatment for obesity. DESIGN: Systematic review and meta-analysis based on a random effects model. DATA SOURCES: Searches of Medline, Embase, and the Cochrane Library from their inception to December 2012 regardless of language or publication status. ELIGIBILITY CRITERIA: Eligible studies were randomised controlled trials with ≥ 6 months of follow-up that included individuals with a body mass index ≥ 30, compared current bariatric surgery techniques with non-surgical treatment, and reported on body weight, cardiovascular risk factors, quality of life, or adverse events. RESULTS: The meta-analysis included 11 studies with 796 individuals (range of mean body mass index at baseline 30-52). Individuals allocated to bariatric surgery lost more body weight (mean difference -26 kg (95% confidence interval -31 to -21)) compared with non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 22.1 (3.2 to 154.3) in a complete case analysis; 5.3 (1.8 to 15.8) in a conservative analysis assuming diabetes remission in all non-surgically treated individuals with missing data) and metabolic syndrome (relative risk 2.4 (1.6 to 3.6) in complete case analysis; 1.5 (0.9 to 2.3) in conservative analysis), greater improvements in quality of life and reductions in medicine use (no pooled data). Plasma triglyceride concentrations decreased more (mean difference -0.7 mmol/L (-1.0 to -0.4) and high density lipoprotein cholesterol concentrations increased more (mean difference 0.21 mmol/L (0.1 to 0.3)). Changes in blood pressure and total or low density lipoprotein cholesterol concentrations were not significantly different. There were no cardiovascular events or deaths reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15% of individuals undergoing malabsorptive bariatric surgery) and reoperations (8%). CONCLUSIONS: Compared with non-surgical treatment of obesity, bariatric surgery leads to greater body weight loss and higher remission rates of type 2 diabetes and metabolic syndrome. However, results are limited to two years of follow-up and based on a small number of studies and individuals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012003317 (www.crd.york.ac.uk/PROSPERO).