Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system

OBJECTIVES: To evaluate the blood pressure-dependent and independent effects of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on major cardiovascular events. METHODS: Using data from 26 large-scale trials comparing an ACEI or an ARB with placebo or another drug class, meta-regression analyses were conducted in which treatment-specific relative risks for major cause-specific outcomes [stroke, major coronary heart disease (CHD) events and heart failure] were regressed against follow-up blood pressure differences. RESULTS: From a total of 146 838 individuals with high blood pressure or an elevated risk of cardiovascular disease, 22 666 major cardiovascular events were documented during follow-up. The analyses showed comparable blood pressure-dependent reductions in risk with ACEI and ARB (P ≥ 0.3 for all three outcomes). The analyses also showed that ACEI produced a blood pressure-independent reduction in the relative risk of CHD of approximately 9% (95% confidence interval 3-14%). No similar effect was detected for ARB, and there was some evidence of a difference between ACEI and ARB in this regard (P = 0.002). For both stroke and heart failure there was no evidence of any blood pressure-independent effects of either ACEI or ARB. CONCLUSION: There are similar blood pressure-dependent effects of ACEI and ARB for the risks of stroke, CHD and heart failure. For ACEI, but not ARB, there is evidence of blood pressure-independent effects on the risk of major coronary disease events.