Aliskiren and valsartan combination therapy for the management of hypertension

Abstract

Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS) are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA), a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI) to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.

Anti-stress and nootropic activity of drugs affecting the renin-angiotensin system in rats based on indirect biochemical evidence

“…10 Although pharmacologic manipulation of the reninangiotensin system with ACEIs and ARBs improves outcomes in hypertension and cardiovascular and renal disease, it provides only partial protection from disease progression. 13 Possible mechanisms for the inadequacies include interruption of negative feedback and a compensatory increase in renin and angiotensin I levels, which can overcome ACE inhibition or result in the production of angiotensin II (Ang II) by non-ACE pathways (i.e. ACE escape).…”

Combination therapy with aliskiren versus ramipril or losartan added to conventional therapy in patients with type 2 diabetes mellitus, uncontrolled hypertension and microalbuminuria

“…In addition, they are not able to completely block RAAS activity because of the reactive rise in renin release induced by the withdrawal of the feedback inhibition exerted by AngII (the so-called short feedback loop), as evidenced by a reactive increase in plasma renin activity (PRA), a well-established cardiovascular risk marker, 18 providing an incomplete cardiorenal protection. 19 The central role of the RAAS in the pathogenesis of diabetic nephropathy is accepted because several studies have shown that ACE-is and ARBs can significantly reduce diabetic nephropathy. [20][21][22][23][24][25] Blockade of the RAAS with ACE-is or ARBs may be delayed; however, this delay does not avoid the progression of diabetic nephropathy towards end-stage renal disease (ESRD).…”

“…31 By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE-is and ARBs. 19 The combination of a DRI and an ARB or an ACE-i is an effective approach for lowering BP and available data indicate that such combinations favourably affect proteinuria, left ventricular mass index and brain natriuretic peptide levels in patients with albuminuria, LVH and HF. 15,19,24,32 Four different trials evaluated the potential cardiorenal effects of aliskiren on morbidity and mortality.…”

“…19 The combination of a DRI and an ARB or an ACE-i is an effective approach for lowering BP and available data indicate that such combinations favourably affect proteinuria, left ventricular mass index and brain natriuretic peptide levels in patients with albuminuria, LVH and HF. 15,19,24,32 Four different trials evaluated the potential cardiorenal effects of aliskiren on morbidity and mortality. 33 One of these, the ALTITUDE, was halted by the recommendation of its Data Monitoring Committee (DMC) because of a higher event rate.…”

Two‐Year Outcomes of Patients Treated With Aliskiren Under Clinical Practice Conditions: Non‐Interventional Prospective Study

“…3 ALIS has been extensively investigated in randomized controlled trials as monotherapy and in various free and single-pill combinations. [4][5][6][7] However, the drug is less well documented with regard to its effectiveness and safety under clinical practice conditions. [8][9][10] Particular interest has been given to the combination of ALIS with an ACE inhibitor or ARB, ie, dual RAS blockade, as ALIS was expected to block the compensatory rise of plasma renin activity (PRA) induced by RAS inhibitors acting downwards in the cascade.…”