When is a meta-analysis conclusive? A guide to Trial Sequential Analysis with an example of remote ischemic preconditioning for renoprotection in patients undergoing cardiac surgery

The pooled estimate of a recent meta‐analysis concluded that rate of reoperation at 1 year was significantly higher in Aortic valve repair (8.82% vs 3.70%) as compared with aortic valve replacement in patients with aortic regurgitation (odds ratio = 2.67, 95% confidence interval [1.08, 3.62], P = .03). We performed a trial sequential analysis using the published data of the meta‐analysis and found the evidence is not strong enough for the conclusion.

No abstract

In this third update of the Cochrane review, there were no differences in effects of homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo on myocardial infarction, death from any cause or adverse events. In terms of stroke, this review found a small difference in effect favouring to homocysteine-lowering interventions in the form of supplements of vitamins B6, B9 or B12 given alone or in combination comparing with placebo.There were uncertain effects of enalapril plus folic acid compared with enalapril on stroke; approximately 143 (95% CI 85 to 428) people would need to be treated for 5.4 years to prevent 1 stroke, this evidence emerged from one mega-trial.Trial sequential analyses showed that additional trials are unlikely to increase the certainty about the findings of this issue regarding homocysteine-lowering interventions versus placebo. There is a need for additional trials comparing homocysteine-lowering interventions combined with antihypertensive medication versus antihypertensive medication, and homocysteine-lowering interventions at high doses versus homocysteine-lowering interventions at low doses. Potential trials should be large and co-operative.