Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker

Abstract

Abstract-Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (nϭ23), ramipril (nϭ21), or irbesartan (nϭ23). In the diuretic combination study, . Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (PϽ0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased ( Key Words: aliskiren Ⅲ ambulatory blood pressure measurement Ⅲ combination therapy Ⅲ hypertension Ⅲ plasma renin activity Ⅲ renin inhibitor Ⅲ renin-angiotensin-aldosterone system A ctivation of the renin-angiotensin (Ang)-aldosterone system (RAAS) plays an important role in the development of hypertension and end-organ damage. 1 Indeed, pretreatment plasma renin activity (PRA) has been shown to be a risk factor for myocardial infarction in hypertensive patients. 2,3 RAAS suppression is, therefore, an important goal of antihypertensive therapy, and RAAS inhibitors, such as Ang-converting enzyme (ACE) inhibitors and Ang receptor blockers (ARBs), have proven to be highly successful treatments for hypertension, heart failure, and related cardiovascular disorders. 4 However, optimized RAAS suppression is difficult to achieve with currently available antihypertensive agents, because ACE inhibitors, ARBs, and diuretics all activate compen-

Aliskiren – an antihypertensive renin inhibitor in the treatment of patients with chronic kidney disease

“…Clinical studies showed that aliskiren lowers SBP and DBP both in younger and elderly hypertensive patients [40], and that greater antihypertensive effect is achieved when given aliskiren in combination with a thiazide diuretic, other blockers of the RAAS system, or a calcium antagonist [41]. The APOLLO trail (The Aliskiren Prevention of Later Life Outcomes) showed that the administration of the combination of aliskiren and hydrochlorothiazide or amlodipine, and used other background antihypertensive drugs (mean of 1.5 drugs), was associated with an anticipated SBP reduction of 10 mmHg and appeared to be safe in the elderly [42].…”

Pretreatment levels of plasma renin activity predict ambulatory blood pressure response to valsartan in essential hypertension

“…[1][2][3] To date, several investigators have studied the association of pretreatment plasma renin activity (PRA) levels with ambulatory blood pressure (ABP) responses to ARBs in essential hypertension. [4][5][6] Recently, we showed that ABP reductions by telmisartan were significantly smaller in hypertensive patients with lower PRA levels than in those with higher PRA levels. 4 However, it is uncertain whether the same is true of all ARBs.…”

“…These findings are well in agreement with our earlier observation regarding telmisartan, 4 and earlier observations by other investigators regarding losartan 5 and irbesartan. 6 Therefore, measurements of pretreatment PRA levels are thought to be useful to predict the ABPlowering effects of ARBs, irrespective of drugs, and should be performed routinely before the initiation of antihypertensive medication, especially in untreated and newly diagnosed patients with essential hypertension.…”

“…[1][2][3] Therefore, monotherapy with a RAS blocker, such as an ARB or a renin inhibitor, 5,6,10 may not be suitable for uncomplicated patients with low-renin hypertension who are free from congestive heart failure, diabetes mellitus or chronic kidney disease.…”

“…K It is assumed that patients with lower renin hypertension respond less to monotherapy with a RAS blocker, such as an ARB, than those with higher renin hypertension. K Although several investigators have suggested that some kinds of ARBs show ABP-lowering effects dependent on pretreatment PRA levels in patients with essential hypertension, [4][5][6] it is uncertain whether the same is true of valsartan.…”