Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system.
OBJECTIVE
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 >or= 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.


CONCLUSIONS
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.
George Institute for International Health, University of Sydney, PO Box M201, Missenden Road, Sydney, NSW 2050, Australia. fturnbull@george.org.au
Turnbull
F
F
Neal
B
B
Pfeffer
M
M
Kostis
J
J
Algert
C
C
Woodward
M
M
Chalmers
J
J
Zanchetti
A
A
MacMahon
S
S
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012680:Sensitivity and Specificity
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors