Some evidence suggests that long-term
angiotensin-converting enzyme (ACE) inhibition may become less effective, thereby increasing
angiotensin II levels, which could be inhibited by the addition of an
angiotensin receptor blocker. We conducted a meta-analysis of randomized trials with searches of MEDLINE, EMBASE, and Cochrane databases. Overall, the combination of an
ACE inhibitor and an
angiotensin receptor blocker reduced ambulatory blood pressure by 4.7/3.0 mm Hg (95% confidence interval [CI], 2.9 to 6.5/1.6 to 4.3) compared with
ACE inhibitor monotherapy and 3.8/2.9 mm Hg (2.4 to 5.3/0.4 to 5.4) compared with
angiotensin receptor blocker monotherapy. Clinic blood pressure was reduced by 3.8/2.7 mm Hg (0.9 to 6.7/0.8 to 4.6) and 3.7/2.3 mm Hg (0.4 to 6.9/0.2 to 4.4) compared with
ACE inhibitor and
angiotensin receptor blocker, respectively. However, the majority of these studies used submaximal doses or once-daily dosing of shorter-acting
ACE inhibitors and, when a larger dose of shorter-acting
ACE inhibitor was given or a longer-acting
ACE inhibitor was used, there was generally no additive effect of the
angiotensin receptor blocker on blood pressure.
Proteinuria was reduced by the combination compared with
ACE inhibitor and
angiotensin receptor blocker monotherapy, an effect that was independent of blood pressure in several studies, suggesting that the combination could have benefits in proteinuric nephropathies. None of the studies was of sufficient size and duration to determine whether there may be safety concerns. In conclusion, although there is a small additive effect on blood pressure with an
ACE inhibitor-
angiotensin receptor blocker combination, the routine use of this combination in uncomplicated
hypertension is not recommended until more carefully controlled studies are performed.