Geographic variation in the statin trials: Underrepresentation of Asian populations

Abstract

Globalisation has seen a shift towards international multicentre randomised controlled trials (RCTs). The amalgamation of heterogenous patient populations is thought to be responsible for the geographic variation in treatment effect noted in recent trials. Furthermore, there is significant underrepresentation of lower- income countries in cardiovascular disease (CVD) research. These issues raise important questions about the generalisability of these trial results. Given the central role of statin therapy in CVD risk reduction, we evaluated for geographic variation in treatment effect in the primary and secondary prevention statin RCTs. We conducted a comprehensive literature search using the terms: "statin", "coronary disease", "reduce" and "cholesterol". We included statin RCTs with >1000 participants, therapy >2 years and CVD outcomes. We analysed each study for regional recruitment data and geographic subgroup analysis. From an initial 2154 studies, we identified 20 eligible for inclusion. This amounted to 138,612 participants across multiple continents including Europe 69,086 (49.8%), Asia 14,672 (10.6%), South America 5128 (3.7%), North America 33,393 (24.1%), Oceania 9445 (6.8%) and Africa 2801 (2%). Data were unavailable for 4087 (2.9%) participants. Despite together comprising 35% of the world's population, China and India represented only 2.7% and 1.3% of the studied population respectively. None of the 6 multi-continent trials provided regional analysis. We were unable to identify significant geographic variation in the outcomes of the statin RCTs, primarily due to a lack of data. We also observed regarding statin RCT data, there is limited involvement of countries with the greatest burden of CVD.