Figure 3
Effect of Rosiglitazone on Adverse Clinical Outcomes. For each adverse clinical outcome, the pooled effect of rosiglitazone in different trial groupings is shown using Peto OR (which includes trials with events) and RD (which includes trials both with and without events). The RD analysis includes trials with 24 or more weeks of drug exposure listed on the manufacturer’s web site (http://ctr.gsk.co.uk/Summary/rosiglitazone/studylist.asp) meeting the inclusion criteria of the original meta-analysis [1]. In addition to trials included in the original meta-analysis [1], we also include 6 additional trials with an active control group (BRL 49653/282, BRL 49653/369, BRL 49653/392, BRL 49653/207, BRL 49653/325, 49653/109), 5 additional trials comparing rosiglitazone to placebo (49653/044, 49653/096, BRL 49653/131, 49653/390, 49653/452), and one additional 4-armed trial with some arms differing only by rosiglitazone therapy (SB-797620/004). For myocardial ischemia and cerebrovascular morbidity individual trials did not specify which patients had more than one adverse event. Consequently,if there were events in more than one category, we took the most conservative approach that the least number of patients in a particular trial arm had all these adverse events. Alternatively, using the least conservative approach by assuming that each adverse event occurred in a different patient, the cerebrovascular result did not significantly change and the p-value for the myocardial ischemia results decreased.
(1) Nissen and Wolski refers to the original meta-analysis [1].
(2) This analysis includes data from all trials in the original meta-analysis [1] in addition to the RECORD trial [5].
(3) This analysis includes only trials in which the sole difference between the intervention and control groups is rosiglitazone therapy. Compared to the original analysis, this excludes trials AVM100264, 49653/020, 49653/080, 49653/097, 49653/137, SB-712753/009, and ADOPT. It excludes one arm in each of the 3-armed trials 49653/093, 49653/079, and SB-712753/007. It also excludes RECORD.
Abbreviations: CI – confidence interval; N – number of trials included in each meta-analysis; OR – Odds Ratio; RD – Risk Difference; RSG – rosiglitazone.