Key result
Olmesartan medoxomil 40 mg significantly increased 24-hour plasma renin activity compared to placebo (P<.0001), indicating more prolonged AT1 receptor blockade than valsartan or irbesartan.
Why the study?
Do angiotensin receptor blockers (olmesartan, valsartan, irbesartan) increase ambulatory plasma renin activity compared to placebo in healthy subjects?
RCT (n=40)
Do angiotensin receptor blockers (olmesartan, valsartan, irbesartan) increase ambulatory plasma renin activity compared to placebo in healthy subjects?
p-value: p=<.0001
Olmesartan 40 mg provides a more prolonged AT1 receptor blockade than valsartan (up to 320 mg) or irbesartan (300 mg), as measured by 24-hour ambulatory plasma renin activity.
Olmesartan 40 mg was associated with more prolonged AT1 blockade than other ARBs; leaves open differential efficacy in hypertension.
BACKGROUND: Plasma renin activity (PRA), measured under controlled conditions, is a marker of the degree and persistence of renin-angiotensin system blockade. METHODS: Two similarly designed five-way crossover studies evaluated angiotensin II type 1 (AT1) receptor blockade-induced changes in PRA in quietly seated, ambulatory volunteers who were ingesting uncontrolled diets. At weekly intervals, PRA was measured during the 24 h after administration of placebo, olmesartan medoxomil (20 or 40 mg), or valsartan (80 or 160 mg) (Study CS866-445), or placebo, olmesartan medoxomil (40 mg), valsartan (160 or 320 mg), or irbesartan (300 mg) (Study CS866-448). The primary end point was change in PRA relative to placebo from predose to 24 h postdose (DeltaPRA24). RESULTS: In the 20 subjects who completed each study, there was a direct relationship between baseline PRA and DeltaPRA24 for all doses. Subjects with low PRA (<0.65 ng/mL/h) exhibited very low absolute increases in PRA. The DeltaPRA(24) increased significantly with olmesartan medoxomil 20 mg (P<.01) and 40 mg (P<.001) and valsartan 160 mg (P<.05) but not with valsartan 80 mg. In the second study (in which baseline PRA was lower), DeltaPRA24 increased with olmesartan medoxomil 40 mg (P<.0001), valsartan 320 mg (P<.01), and irbesartan 300 mg (P<.01) but not with valsartan 160 mg. The DeltaPRA24 was greatest with olmesartan medoxomil 40 mg and was dose-related for olmesartan medoxomil but not for valsartan. CONCLUSIONS: The greater DeltaPRA24 with olmesartan medoxomil 40 mg indicates a more prolonged AT1 receptor blockade than with valsartan 80, 160, or 320 mg or irbesartan 300 mg. A routine, clinic ambulatory PRA level can be used as a biochemical marker of the persistence and degree of AT1 receptor blockade in subjects without suppressed PRA levels.
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Jones et al. (2007) conducted an RCT in Healthy, normal subjects (n=40). Angiotensin Receptor Blockers (Olmesartan, Valsartan, Irbesartan) vs. Placebo was evaluated on Change in plasma renin activity relative to placebo from predose to 24 h postdose (DeltaPRA24) (p=<.0001). Olmesartan medoxomil 40 mg significantly increased 24-hour plasma renin activity compared to placebo (P<.0001), indicating more prolonged AT1 receptor blockade than valsartan or irbesartan.
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