Aim: To quantify the effects of hormone‐replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women.
Methods: Comprehensive searches of electronic databases were ...performed from April 1966 to October 2004. We included randomized controlled trials that were of at least 8 weeks duration and evaluated the effect of HRT on metabolic, inflammatory or thrombotic components. Insulin resistance was calculated by homeostasis model assessment (HOMA‐IR). Subgroup analysis evaluated the effects for transdermal and oral treatment and for diabetic and non‐diabetic women.
Results: Pooled results of 107 trials showed that HRT reduced abdominal fat −6.8% (CI, −11.8 to −1.9%), HOMA‐IR −12.9% (CI, −17.1 to −8.6%) and new‐onset diabetes relative risk 0.7 (CI, 0.6–0.9) in women without diabetes. In women with diabetes, HRT reduced fasting glucose −11.5% (CI, −18.0 to −5.1%) and HOMA‐IR −35.8% (CI, −51.7 to −19.8%). HRT also reduced low‐density lipoprotein/high‐density lipoprotein cholesterol ratio −15.7% (CI, −18.0 to −13.5%), lipoprotein(a) Lp(a) −25.0% CI, −32.9 to −17.1%), mean blood pressure −1.7% (CI, −2.9 to −0.5%), E‐selectin −17.3% (CI, −22.4 to −12.1%), fibrinogen −5.5% (CI, −7.8 to −3.2%) and plasminogen activator inhibitor‐1 −25.1% (CI, −33.6 to −15.5%). Oral agents produced larger beneficial effects than transdermal agents, but increased C‐reactive protein (CRP) 37.6% (CI, 17.4–61.3%) and decreased protein S −8.6% CI, −13.1 to −4.1%), while transdermal agents had no effect.
Conclusions: HRT reduces abdominal obesity, insulin resistance, new‐onset diabetes, lipids, blood pressure, adhesion molecules and procoagulant factors in women without diabetes and reduced insulin resistance and fasting glucose in women with diabetes. Oral agents adversely affected CRP and protein S, while transdermal agents had no effects.
Beta-blocker therapy has a proven mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have ...traditionally been considered contraindicated in patients with chronic obstructive pulmonary disease (COPD).
To assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD.
A comprehensive search of the Cochrane Airways Group Specialised Register (derived from systematic searches of CENTRAL, MEDLINE, EMBASE and CINAHL) was carried out to identify randomised blinded controlled trials from 1966 to May 2005. We did not exclude trials on the basis of language.
Randomised, blinded, controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1) or symptoms in patients with COPD.
Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug.
Eleven studies of single-dose treatment and 9 of treatment for longer durations, ranging from 2 days to 12 weeks, met selection criteria. Cardioselective beta-blockers, given as a single dose or for longer duration, produced no change in FEV1 or respiratory symptoms compared to placebo, and did not affect the FEV1 treatment response to beta2-agonists. A subgroup analysis revealed no change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component.
Cardioselective beta-blockers, given to patients with COPD in the identified studies did not produce adverse respiratory effects. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should not be routinely withheld from patients with COPD.
Abstract Background There is uncertainty over the risks and benefits of hormone therapy. We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy on total mortality in younger ...postmenopausal women. This analysis synthesizes evidence from different sources, taking into account varying views on the issue. Methods A comprehensive search from 1966 through January 2008 identified randomized controlled trials of at least 6 month's duration that evaluated hormone therapy in women with mean age <60 years and reported at least one death, and prospective observational cohort studies that evaluated the relative risk of mortality associated with hormone therapy after adjustment for confounding variables. Results The results were synthesized using a hierarchical random-effects Bayesian meta-analysis. The pooled results from 19 randomized trials, with 16,000 women (mean age 55 years) followed for 83,000 patient-years, showed a mortality relative risk of 0.73 (95% credible interval 0.52-0.96). When data from 8 observational studies were added to the analysis, the resultant relative risk was 0.72 (credible interval 0.62-0.82). The posterior probability that hormone therapy reduces total mortality in younger women is almost 1. Conclusions The synthesis of data using Bayesian meta-analysis indicates a reduction in mortality in younger postmenopausal women taking hormone therapy compared with no treatment. This finding should be interpreted taking into account the potential benefits and harms of hormone therapy.
Beta-blocker therapy has a mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been ...considered contraindicated in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. Comprehensive searches were performed of the EMBASE, MEDLINE and CINAHL databases from 1966 to May 2001, and identified articles and related reviews were scanned. Randomised, blinded, controlled trials that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1
s (FEV1) or symptoms in patients with COPD were included in the analysis. Interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. Outcomes measured were the change in FEV1 from baseline and the number of patients with respiratory symptoms. Eleven studies of single-dose treatment and 8 of continued treatment were included. Cardioselective beta-blockers produced no significant change in FEV1 or respiratory symptoms compared to placebo, given as a single dose (−2.05% 95% CI, −6.05% to 1.96%) or for longer duration (−2.55% CI, −5.94% to 0.84), and did not significantly affect the FEV1 treatment response to beta2-agonists. Subgroup analyses revealed no significant change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component. In conclusion, cardioselective beta-blockers given to patients with COPD do not produce a significant reduction in airway function or increase the incidence of COPD exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should be considered for patients with COPD.
Abstract Purpose We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for ...diabetes. Methods We performed comprehensive English- and non–English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes. Results Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (−5.3%, 95% confidence interval CI, −6.7-−4.0), fasting glucose (−4.5%, CI, −6.0-−3.0), fasting insulin (−14.4%, CI, −19.9-−8.9), calculated insulin resistance (−22.6%, CI, −27.3-−18.0), triglycerides (−5.3%, CI, −10.5-−0.03), and low-density lipoprotein cholesterol (−5.6%, CI, −8.3-−3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years. Conclusion Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials.
beta-Adrenergic agonists exert physiologic effects that are the opposite of those of beta-blockers. beta-Blockers are known to reduce morbidity and mortality in patients with cardiac disease. ...beta(2)-Agonist use in patients with obstructive airway disease has been associated with an increased risk for myocardial infarction, congestive heart failure, cardiac arrest, and acute cardiac death.
To assess the cardiovascular safety of beta(2)-agonist use in patients with obstructive airway disease, defined as asthma or COPD.
A meta-analysis of randomized placebo-controlled trials of beta(2)-agonist treatment in patients with obstructive airway disease was performed, to evaluate the short-term effect on heart rate and potassium concentrations, and the long-term effect on adverse cardiovascular events. Longer duration trials were included in the analysis if they reported at least one adverse event. Adverse events included sinus and ventricular tachycardia, syncope, atrial fibrillation, congestive heart failure, myocardial infarction, cardiac arrest, or sudden death.
Thirteen single-dose trials and 20 longer duration trials were included in the study. A single dose of beta(2)-agonist increased the heart rate by 9.12 beats/min (95% confidence interval CI, 5.32 to 12.92) and reduced the potassium concentration by 0.36 mmol/L (95% CI, 0.18 to 0.54), compared to placebo. For trials lasting from 3 days to 1 year, beta(2)-agonist treatment significantly increased the risk for a cardiovascular event (relative risk RR, 2.54; 95% CI, 1.59 to 4.05) compared to placebo. The RR for sinus tachycardia alone was 3.06 (95% CI, 1.70 to 5.50), and for all other events it was 1.66 (95% CI, 0.76 to 3.6).
beta(2)-Agonist use in patients with obstructive airway disease increases the risk for adverse cardiovascular events. The initiation of treatment increases heart rate and reduces potassium concentrations compared to placebo. It could be through these mechanisms, and other effects of beta-adrenergic stimulation, that beta(2)-agonists may precipitate ischemia, congestive heart failure, arrhythmias, and sudden death.
OBJECTIVE: To assess the effect of hormone therapy (HT) on coronary heart disease (CHD) events in younger and older postmenopausal women.
DESIGN: A comprehensive database search identified ...randomized‐controlled trials of HT of at least 6 months' duration that reported CHD events, defined as myocardial infarction or cardiac death.
MEASUREMENTS: The pooled odds ratios (ORs) for CHD events were reported separately for younger and older women, defined as participants with mean time from menopause of less than or greater than 10 years, or mean age less than or greater than 60 years.
MAIN RESULTS: Pooled data from 23 trials, with 39,049 participants followed for 191,340 patient‐years, showed that HT significantly reduced CHD events in younger women (OR 0.68 confidence interval (C I), 0.48 to 0.96), but not in older women (OR 1.03 CI, 0.91 to 1.16). Hormone therapy reduced events in younger women compared with older women (OR 0.66 CI, 0.46 to 0.95). In older women, HT increased events in the first year (OR 1.47 CI, 1.12 to 1.92), then reduced events after 2 years (OR 0.79 CI, 0.67 to 0.93).
CONCLUSIONS: Hormone therapy reduces the risk of CHD events in younger postmenopausal women. In older women, HT increases, then decreases risk over time.
To assess mortality associated with hormone replacement in younger and older postmenopausal women.
A comprehensive search of MEDLINE, CINAHL, and EMBASE databases was performed to identify randomized ...controlled trials of hormone replacement therapy from 1966 to September 2002. The search was augmented by scanning selected journals through April 2003 and references of identified articles. Randomized trials of greater than 6 months' duration were included if they compared hormone replacement with placebo or no treatment, and reported at least 1 death.
Outcomes measured were total deaths and deaths due to cardiovascular disease, cancer, or other causes. Odds ratios (OR) for total and cause-specific mortality were reported separately for trials with mean age of participants less than and greater than 60 years at baseline.
Pooled data from 30 trials with 26,708 participants showed that the OR for total mortality associated with hormone replacement was 0.98 (95% confidence interval CI, 0.87 to 1.12). Hormone replacement reduced mortality in the younger age group (OR, 0.61; CI, 0.39 to 0.95), but not in the older age group (OR, 1.03; CI, 0.90 to 1.18). For all ages combined, treatment did not significantly affect the risk for cardiovascular or cancer mortality, but reduced mortality from other causes (OR, 0.67; CI, 0.51 to 0.88).
Hormone replacement therapy reduced total mortality in trials with mean age of participants under 60 years. No change in mortality was seen in trials with mean age over 60 years.
Long-acting beta-agonists may increase the risk for fatal and nonfatal asthma exacerbations.
To assess the risk for severe, life-threatening, or fatal asthma exacerbations associated with long-acting ...beta-agonists.
English- and non-English-language searches of MEDLINE, EMBASE, and Cochrane databases; the U.S. Food and Drug Administration Web site; and references of selected reviews through December 2005.
Randomized, placebo-controlled trials that lasted at least 3 months and evaluated long-acting beta-agonist use in patients with asthma. All trials allowed the use of as-needed short-acting beta-agonists.
Outcomes measured were Peto odds ratio (OR) and risk difference of severe exacerbations requiring hospitalization, life-threatening exacerbations requiring intubation and ventilation, and asthma-related deaths. The OR for asthma-related deaths was obtained from the Salmeterol Multi-center Asthma Research Trial (SMART).
Pooled results from 19 trials with 33 826 participants found that long-acting beta-agonists increased exacerbations requiring hospitalization (OR, 2.6 95% CI, 1.6 to 4.3) and life-threatening exacerbations (OR, 1.8 CI, 1.1 to 2.9) compared with placebo. Hospitalizations were statistically significantly increased with salmeterol (OR, 1.7 CI, 1.1 to 2.7) and formoterol (OR, 3.2 CI, 1.7 to 6.0) and in children (OR, 3.9 CI, 1.7 to 8.8) and adults (OR, 2.0 CI, 1.1 to 3.9). The absolute increase in hospitalization was 0.7% (CI, 0.1% to 1.3%) over 6 months. The risk for asthma-related deaths was increased (OR, 3.5 CI, 1.3 to 9.3), with a pooled risk difference of 0.07% (CI, 0.01% to 0.1%).
The small number of deaths limited the reliability in assessing this risk, and 28 studies did not report information on the outcomes of interest.
Long-acting beta-agonists have been shown to increase severe and life-threatening asthma exacerbations, as well as asthma-related deaths.
To assess the effect of cardioselective beta-blockers on respiratory function of patients with reactive airway disease.
Comprehensive searches of the EMBASE, MEDLINE, and CINAHL databases from 1966 ...to May 2001 and scanning of references of the identified articles and related reviews.
Randomized, blinded, placebo-controlled trials that studied the effects of cardioselective beta-blockers on FEV1, symptoms, and the use of inhaled beta2-agonists in patients with reactive airway disease were selected. Interventions studied were the administration of a cardioselective beta-blocker and administration of beta2-agonist after the study drug.
Outcomes measured were the change in FEV1 from baseline, the number of patients with respiratory symptoms, and the use of inhaled beta2-agonists with active treatment compared with placebo.
Nineteen studies on single-dose treatment and 10 studies on continued treatment were included. Administration of a single dose of a cardioselective beta-blocker was associated with a 7.46% (95% CI, 5.59% to 9.32%) decrease in FEV(1) and a 4.63% (CI, 2.47% to 6.78%) increase in FEV1 response to beta-agonist compared with placebo, with no increase in symptoms. Trials lasting from 3 days to 4 weeks produced no significant change in FEV1 (-0.42% CI, -3.74% to 2.91%), symptoms, or inhaler use compared with placebo but maintained an 8.74% (CI, 1.96% to 15.52%) increase in beta-agonist response. No significant treatment effect in terms of FEV1 was found in patients with concomitant chronic obstructive pulmonary disease, whether single doses (change in FEV1, -5.28% CI, -10.03% to -0.54%) or continued treatment (change in FEV1, 1.07% CI, -3.3% to 5.44%) was given.
Cardioselective beta-blockers do not produce clinically significant adverse respiratory effects in patients with mild to moderate reactive airway disease. The results were similar for patients with concomitant chronic airways obstruction. Given their demonstrated benefit in such conditions as heart failure, cardiac arrhythmias, and hypertension, cardioselective beta-blockers should not be withheld from patients with mild to moderate reactive airway disease.
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