The once-daily dose regimen of carvedilol: a meta-analysis approach

Establishing the overall efficacy or safety of a drug requires a unified methodological approach and analysis of all clinical trials that are intended to be summarized. As an example, this article presents the aggregated dose-response relationship and a subgroup analysis (by age) over all studies of the antihypertensive drug carvedilol. The clinical end points were change from baseline of blood pressure and pulse after 2-4 weeks of treatment with a once-daily dose regimen. All antihypertensive trials were reanalyzed using an intent-to-treat principle. Aggregated data (mean, standard deviation, sample size) for each random group within each study were then combined by means of meta-analysis. The results show that the main patient population can be treated adequately with 25 mg of carvedilol q.d. The dose-response curve shows a typical sigmoid shape: a steeper increase from 12.5 to 25 mg of carvedilol and a following flat part (25, 50, and 100 mg of carvedilol q.d.). There is a considerable variation of the results between studies, which is much bigger than the dose-response effect. Most of this variation is due to monocentric trials.