Are cardiovascular trial results systematically different between North America and Europe? A study based on intra-meta-analysis comparisons.

Background: It is often assumed that differences in the efficacy of treatments between countries (or regions) will be neither negligible nor minor and therefore cannot be overlooked when assessing the potential benefit of treatments in one country (or region) on the basis of trials conducted in another country (or region).

Aim: To assess differences in the results of cardiovascular trials between Europe and North America on the basis of data from an extensive collection of trials.

Methods: A systematic search was conducted of Medline (from the year 2005 to 2008) and the Cochrane Library (from 2000 to 2008) for all meta-analyses of randomized controlled trials aimed at treating and preventing cardiovascular disease. Within each meta-analysis that satisfied given criteria, trial results were compared between Europe and North America with respect to a fatal and/or non-fatal endpoint by forming separate estimates of treatment efficacy for each of these continents.

Results: The literature search found 59 meta-analyses that satisfied all the inclusion criteria. For most meta-analyses, it was the case that relative to the control, the intervention was more favoured in trials conducted in Europe than in North America with regard to both fatal endpoints (28 out of 43 meta-analyses) and non-fatal endpoints (28 out of 40 meta-analyses). However, it was only with regard to non-fatal endpoints that this imbalance turned out to be statistically significant at the 5% level (P=0.017). Also, the lack of statistically significant differences in trial results between Europe and North America within individual meta-analyses meant that it was not possible to determine for which types of intervention these intercontinental differences are likely to be more pronounced than others.

Conclusion: There is some evidence to support the theory that, relative to controls, interventions are more favoured in cardiovascular trials conducted in Europe than in North America, when treatment efficacy is measured in terms of a non-fatal endpoint. However, the overall support for systematic differences in cardiovascular trial results between Europe and North America is weak, which may be surprising given the amount of data collected.