Effects of different blood pressure-lowering regimens on major cardiovascular events in major patient subgroups

Background Cardiovascular disease is a leading cause of mortality and morbidity worldwide. Blood pressure is the single, most important risk factor for cardiovascular disease; nearly two-thirds of all strokes and approximately half of all ischaemic heart disease events are attributable to non-optimal blood pressure. The evidence from individual randomised trials of blood pressure lowering regimens suggests that that protection from major cardiovascular events can be achieved by lowering blood pressure, even among those with so-called ‘normal’ blood pressures. However, many trials are not sufficiently powered to demonstrate modest but clinically important differences in the effects of different classes of drug on the risk of cardiovascular disease. As a result, there is considerable uncertainty about the relative effectiveness of different drug classes. Reliable and precise information about the effects of treatment is central to the management of cardiovascular risk in millions of people worldwide. The aim of the research contributing to this thesis was to generate high quality evidence about the effects of a range of blood pressure lowering regimens on major cardiovascular outcomes in important patient subgroups. Methods The research uses prospectively-planned overviews (meta-analyses) of large randomised trials to generate precise estimates of treatment effect. The trials contributing to the overviews were those participating in the Blood Pressure Lowering Treatment Trialists’ Collaboration. Data from all relevant trials were submitted to the Collaboration Secretariat based at the George Institute for International Health in Sydney, Australia for inclusion in analyses. Data were combined using standard meta-analytic techniques and reported as pooled point estimates and 95% confidence intervals for the six pre-specified primary outcomes of stroke, coronary heart disease, heart failure, cardiovascular death and total mortality. The analyses comprised three main components: (1) one main set of overview analyses to examine treatment effects in the overall study population; (2) three sets of overview analyses to examine treatment effects in subgroups of younger and older patients, men and women and patients with and without diabetes; and (3) a series of post-hoc analyses (meta-analysis and meta-regression analysis) to examine the relative contributions of blood pressure-dependent and independent effects of two main classes of blood pressure drugs, ACE-I inhibitors and angiotensin receptor blockers