Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes - Principal results of the Conduit Artery Function Evaluation (CAFE) study

Background - Different blood pressure (BP)-lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation ( CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol +/- thiazide-based versus amlodipine +/- perindopril-based therapy) on derived central aortic pressures and hemodynamics. Methods and Results - The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (Delta 0.7 mm Hg; 95% CI, -0.4 to 1.7; P = 0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen ( central aortic systolic BP, Delta 4.3 mm Hg; 95% CI, 3.3 to 5.4; P < 0.0001; central aortic pulse pressure, Delta 3.0 mm Hg; 95% CI, 2.1 to 3.9; P < 0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc - defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort ( unadjusted, P < 0.0001; adjusted for baseline variables, P < 0.05). Conclusions - BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.