Abstract 3620: Suppression of the Renin System By The Novel Orally Effective Direct Renin Inhibitor Aliskiren: A Pooled Analysis of 1612 Patients With Hypertension
Background: Elevated plasma renin activity (PRA) is a marker of renin system activation, and is associated with an increased risk of myocardial infarction in untreated hypertensive patients. Angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) and diuretics stimulate a compensatory rise in PRA, although there is no evidence that this rise is associated with increased risk. The direct renin inhibitor aliskiren acts by suppressing PRA. This study determined the effects of aliskiren on PRA when used in combination with agents that elevate PRA.
Methods: This was a pooled analysis of the effects of aliskiren on PRA and renin concentration (RC) across 4 randomized, double-blind trials in patients with hypertension. Changes in log-transformed PRA (available for 1593 patients) and RC (1612 patients) with pooled aliskiren monotherapy, comparator antihypertensive and combination treatment groups were compared with pooled placebo (PBO) using an analysis of covariance model with treatment as factor and baseline value as covariate.
Results: Aliskiren monotherapy pooled across all doses (75– 600 mg) caused a highly significant 70.3% reduction vs PBO in PRA despite a 199% increase in RC (Table⇓). In contrast with aliskiren, the compensatory increases in RC stimulated by the ARB irbesartan (150 mg), the ACEI ramipril (10 mg) and the diuretic hydrochlorothiazide (HCTZ; 6.25–25 mg) were associated with a rise in PRA. However, aliskiren significantly suppressed PRA (p<0.0001) in combination with the ACEI or diuretic (ARB combination not studied), despite synergistic increases in RC with combination treatment (by 315% with aliskiren/ACEI and 406% with aliskiren/HCTZ).
Conclusions: Aliskiren suppresses PRA when given alone or in combination with agents that increase PRA. Aliskiren is therefore a useful adjunct to other antihypertensive treatments, offering potentially improved end-organ protection by optimizing renin system suppression.