CiteULike: omalbam's meta-analysis

Antiandrogens for the Treatment of Hirsutism: A Systematic Review and Metaanalyses of Randomized Controlled Trials

Brian Swiglo — 2008-04-21T17:04:06-00:00

J Clin Endocrinol Metab, Vol. 93, No. 4. (1 April 2008), pp. 1153-1160.

Context: The relative efficacy of antiandrogens for the treatment of hirsutism remains unclear. Objective: We performed a systematic review and metaanalyses of randomized controlled trials (RCTs) evaluating the effect of antiandrogens on hirsutism. Data Sources: We used librarian-designed search strategies for MEDLINE, EMBASE, and Cochrane CENTRAL (up to May 2006), review of reference lists, and contact with hirsutism experts to identify eligible RCTs. Study Selection: Eligible studies were RCTs of at least 6 months of antiandrogen use in women with hirsutism. Reviewers, with acceptable chance-adjusted agreement (kappa = 0.72), independently assessed eligibility. Data Extraction: Reviewers used structured forms to assess and collect methodological quality (allocation concealment, blinding, and loss to follow-up) and study data. Data Synthesis: Of 348 candidate studies, 12 were eligible (18 comparisons). Their methodological quality was low. Random-effects metaanalyses showed that compared with placebo, antiandrogens reduce Ferriman-Gallwey scores by 3.9 [95% confidence interval (CI), 2.35.4; inconsistency (I2) = 0%]. When compared with metformin, spironolactone reduced hirsutism scores by 1.3 (CI, 0.032.6) and flutamide by 5.0 (CI, 3.07.0; I2 = 0%). For these interventions, two to five women need to receive treatment for one to notice improvement. Spironolactone or finasteride in combination with contraceptives (1.7; CI, 0.13.3; I2 = 0%) or flutamide with metformin (4.6; CI, 1.37.9; I2 = 40%) appear superior to monotherapy with contraceptives and metformin, respectively. Only three RCTs reported patient self-assessments of hirsutism. Conclusions: Weak evidence suggests antiandrogens are mildly effective agents for the treatment of hirsutism. 10.1210/jc.2007-2430

Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials

Robin Christensen — 2008-02-18T04:17:32-00:00

The Lancet, Vol. 370, No. 9600., pp. 1706-1713.

SummaryBackground Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant.Methods We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo.Findings Patients given rimonabant had a 4[middle dot]7 kg (95% CI 4[middle dot]1-5[middle dot]3 kg; p<0[middle dot]0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1[middle dot]4; p=0[middle dot]0007; number needed to harm=25 individuals [95% CI 17-58]), and 1[middle dot]4 times more serious adverse events (OR=1[middle dot]4; p=0[middle dot]03; number needed to harm=59 [27-830]). Patients given rimonabant were 2[middle dot]5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2[middle dot]5; p=0[middle dot]01; number needed to harm=49 [19-316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3[middle dot]0; p=0[middle dot]03; number needed to harm=166 [47-3716]).Interpretation Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety--despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.

Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials

Giovanni Strippoli — 2008-03-22T20:38:36-00:00

BMJ, Vol. 336, No. 7645. (22 March 2008), pp. 645-651.

Objective To analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations). Design Meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006). Study selection Randomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease. Data extraction and analysis Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model. Results Fifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference 42.28 mg/dl (1.10 mmol/l), 95% confidence interval 47.25 to 37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; 43.12 mg/dl (1.12 mmol/l), 47.85 to 38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; 0.73 g/24 hour, 0.95 to 0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), 2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only. Conclusion Statins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias. 10.1136/bmj.39472.580984.AE

Paclitaxel-eluting coronary stents in patients with diabetes mellitus: pooled analysis from 5 randomized trials.

AJ Kirtane — 2008-03-11T16:02:02-00:00

J Am Coll Cardiol, Vol. 51, No. 7. (19 February 2008), pp. 708-715.

OBJECTIVES: We sought to examine the safety and efficacy of paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM). BACKGROUND: Compared with patients without DM, patients with DM undergoing percutaneous coronary intervention are at increased risk for mortality and restenosis. The safety of drug-eluting stents in diabetic patients has recently been called into question by a published meta-analysis of randomized trials. METHODS: Patient-level data were pooled from 5 prospective, double-blind, randomized trials of PES versus bare-metal stents (BMS) (n = 3,513). Safety and efficacy outcomes through 4 years of follow-up were assessed among the 827 randomized patients (23.6%) with DM. RESULTS: Patients treated with PES and BMS has similar baseline characteristics among both the diabetic and nondiabetic cohorts within these trials. At 4-year follow-up, there were no significant differences between PES and BMS among diabetic patients in the rates of death (8.4% vs. 10.3%, respectively, p = 0.61), myocardial infarction (6.9% vs. 8.9%, p = 0.17), or stent thrombosis (1.4% vs. 1.2%, p = 0.92). Treatment of diabetic patients with PES compared with treatment with BMS was associated with a significant and durable reduction in target lesion revascularization over the 4-year follow-up period (12.4% vs. 24.7%, p < 0.0001). The relative safety and efficacy of PES compared with the relative safety and efficacy of BMS in diabetic patients extended to both those requiring and not requiring insulin. CONCLUSIONS: In these 5 randomized trials in which patients with single, primarily noncomplex lesions were enrolled, treatment with PES compared with treatment with BMS was safe and effective, resulting in markedly lower rates of target lesion revascularization at 4 years, with similar rates of death, myocardial infarction, and stent thrombosis.

Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus.

S Bolen — 2008-02-04T18:55:56-00:00

Ann Intern Med, Vol. 147, No. 6. (18 September 2007), pp. 386-399.

BACKGROUND: As newer oral diabetes agents continue to emerge on the market, comparative evidence is urgently required to guide appropriate therapy. PURPOSE: To summarize the English-language literature on the benefits and harms of oral agents (second-generation sulfonylureas, biguanides, thiazolidinediones, meglitinides, and alpha-glucosidase inhibitors) in the treatment of adults with type 2 diabetes mellitus. DATA SOURCES: The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched from inception through January 2006 for original articles and through November 2005 for systematic reviews. Unpublished U.S. Food and Drug Administration and industry data were also searched. STUDY SELECTION: 216 controlled trials and cohort studies and 2 systematic reviews that addressed benefits and harms of oral diabetes drug classes available in the United States. DATA EXTRACTION: Using standardized protocols, 2 reviewers serially abstracted data for each article. DATA SYNTHESIS: Evidence from clinical trials was inconclusive on major clinical end points, such as cardiovascular mortality. Therefore, the review was limited mainly to studies of intermediate end points. Most oral agents (thiazolidinediones, metformin, and repaglinide) improved glycemic control to the same degree as sulfonylureas (absolute decrease in hemoglobin A1c level of about 1 percentage point). Nateglinide and alpha-glucosidase inhibitors may have slightly weaker effects, on the basis of indirect comparisons of placebo-controlled trials. Thiazolidinediones were the only class that had a beneficial effect on high-density lipoprotein cholesterol levels (mean relative increase, 0.08 to 0.13 mmol/L [3 to 5 mg/dL]) but a harmful effect on low-density lipoprotein (LDL) cholesterol levels (mean relative increase, 0.26 mmol/L [10 mg/dL]) compared with other oral agents. Metformin decreased LDL cholesterol levels by about 0.26 mmol/L (10 mg/dL), whereas other oral agents had no obvious effects on LDL cholesterol levels. Most agents other than metformin increased body weight by 1 to 5 kg. Sulfonylureas and repaglinide were associated with greater risk for hypoglycemia, thiazolidinediones with greater risk for heart failure, and metformin with greater risk for gastrointestinal problems compared with other oral agents. Lactic acidosis was no more common in metformin recipients without comorbid conditions than in recipients of other oral diabetes agents. LIMITATIONS: Data on major clinical end points were limited. Studies inconsistently reported adverse events other than hypoglycemia, and definitions of adverse events varied across studies. Some harms not assessed in trials or observational studies may have been overlooked. CONCLUSIONS: Compared with newer, more expensive agents (thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides), older agents (second-generation sulfonylureas and metformin) have similar or superior effects on glycemic control, lipids, and other intermediate end points. Large, long-term comparative studies are needed to determine the comparative effects of oral diabetes agents on hard clinical end points.

Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis

George Krasopoulos — 2008-01-25T15:46:06-00:00

BMJ, Vol. 336, No. 7637. (26 January 2008), pp. 195-198.

Objective To determine if there is a relation between aspirin "resistance" and clinical outcomes in patients with cardiovascular disease. Design Systematic review and meta-analysis. Data source Electronic literature search without language restrictions of four databases and hand search of bibliographies for other relevant articles. Review methods Inclusion criteria included a test for platelet responsiveness and clinical outcomes. Aspirin resistance was assessed, using a variety of platelet function assays. Results 20 studies totalling 2930 patients with cardiovascular disease were identified. Most studies used aspirin regimens, ranging from 75-325 mg daily, and six studies included adjunct antiplatelet therapy. Compliance was confirmed directly in 14 studies and by telephone or interviews in three. Information was insufficient to assess compliance in three studies. Overall, 810 patients (28%) were classified as aspirin resistant. A cardiovascular related event occurred in 41% of patients (odds ratio 3.85, 95% confidence interval 3.08 to 4.80), death in 5.7% (5.99, 2.28 to 15.72), and an acute coronary syndrome in 39.4% (4.06, 2.96 to 5.56). Aspirin resistant patients did not benefit from other antiplatelet treatment. Conclusion Patients who are resistant to aspirin are at a greater risk of clinically important cardiovascular morbidity long term than patients who are sensitive to aspirin. 10.1136/bmj.39430.529549.BE

Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis

Andrea Isidori — 2005-08-18T10:48:04-00:00

Clinical Endocrinology, Vol. 63, No. 3. (September 2005), pp. 280-293.

Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis

David Jenkins — 2008-01-15T00:49:10-00:00

CMAJ, Vol. 178, No. 2. (15 January 2008), pp. 157-164.

Background: A recent Cochrane meta-analysis did not confirm the benefits of fish and fish oil in the secondary prevention of cardiac death and myocardial infarction. We performed a meta-analysis of randomized controlled trials that examined the effect of fish-oil supplementation on ventricular fibrillation and ventricular tachycardia to determine the overall effect and to assess whether heterogeneity exists between trials. Methods: We searched electronic databases (MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, CINAHL) from inception to May 2007. We included randomized controlled trials of fish-oil supplementation on ventricular fibrillation or ventricular tachycardia in patients with implantable cardioverter defibrillators. The primary outcome was implantable cardioverter defibrillator discharge. We calculated relative risk [RR] for outcomes at 1-year follow-up for each study. We used the DerSimonian and Laird random-effects methods when there was significant heterogeneity between trials and the Mantel-Hanzel fixed-effects method when heterogeneity was negligible. Results: We identified 3 trials of 12 years' duration. These trials included a total of 573 patients who received fish oil and 575 patients who received a control. Meta-analysis of data collected at 1 year showed no overall effect of fish oil on the relative risk of implantable cardioverter defibrillator discharge. There was significant heterogeneity between trials. The second largest study showed a significant benefit of fish oil (relative risk [RR] 0.74, 95% confidence interval [CI] 0.560.98). The smallest showed an adverse tendency at 1 year (RR 1.23, 95% CI 0.921.65) and significantly worse outcome at 2 years among patients with ventricular tachycardia at study entry (log rank p = 0.007). Conclusion: These data indicate that there is heterogeneity in the response of patients to fish-oil supplementation. Caution should be used when prescribing fish-oil supplementation for patients with ventricular tachycardia. 10.1503/cmaj.070261