Late-Breaking Clinical Trial Abstracts

Brachial blood pressure (BP) measurements are used to monitor the efficacy of BP lowering drugs. Different BP lowering drugs could have differing effects on central aortic pressures and thus cardiovascular outcome, despite similar effects on brachial BP. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) examined the impact of two blood pressure lowering regimens; conventional therapy (atenololthiazide), versus contemporary therapy (amlodipineperindopril) in 19,257 patients with hypertension. The CAFE study, a sub-study of ASCOT, provides the first analysis of the impact of two different BP lowering regimens on derived central aortic pressures and hemodynamics. Hypothesis: i) different BP-lowering regimens will produce different effects on central aortic pressures/hemodynamics despite similar brachial blood pressures, and ii) this would contribute to different clinical outcomes in ASCOT. Design/Methods: The CAFE study recruited 2,199 patients in 5 ASCOT study centres. CAFE baseline demographics were representative of the ASCOT population. Radial artery applanation tonometry and pulse wave analysis (SphygmoCor ) was used to derive central aortic pressures and hemodynamic indices. Over 17,000 central hemodynamic measurements were recorded on repeated visits, for up to 5 years. Results: Brachial BP differed little between treatment groups (-0.7/1.6mmHg, in favour of amlodipine). However, there were substantial reductions in trial-averaged values for central aortic pressures and hemodynamic indices in favour of the amlodipine regimen; central aortic systolic BP (-4.3mmHg 0.5,0.0001), central aortic pulse pressure (-3.0mmHg 0.5, 0.0001) and augmentation index:(-5.8% 0.4, 0.0001). In ASCOT, amlodipine-based treatment was associated with significant reductions in major cardiovascular and renal outcomes and death. In the CAFE cohort within ASCOT, central pulse pressure was a significant determinant of total cardiovascular and renal events/procedures, using a Cox proportional hazards model (unadjusted:p0.0001, adjusted for baseline variables: p0.05). Conclusion: The CAFE study demonstrates for the first time in a large clinical outcomes trial, that BP lowering drugs have profoundly different effects on central aortic pressures and hemodynamics, despite a similar impact on brachial blood pressure. Brachial BP is therefore, an imperfect surrogate for the effects of BP lowering drugs on central aortic pressures. Moreover, central pulse pressure appears to be an important determinant of clinical outcomes. These findings: i) provide a novel mechanism to explain the different clinical outcomes between the two BP-treatment arms in ASCOT and potentially other BP-lowering treatment trials, and ii) may have significant implications for treatment guidelines.