Combination therapy with aliskiren and amlodipine in hypertension: treatment rationale and clinical results

Abstract

Optimal antihypertensive therapy requires a multimodal approach based on lifestyle modification and, for most individuals, combination drug therapy. Recommendations from experts suggest that a combination of an agent that blocks the renin–angiotensin system (RAS), together with a vasodilator (generally a calcium-channel blocker or a thiazide-type diuretic), is most likely to control blood pressure and provide the widest overall cardiovascular protection. Understanding the opportunities afforded by the combination of RAS blockade with a calcium-channel blocker requires a discussion of basic and clinical science data. One new concept is that of ‘global’ or total RAS blockade. The impact of the RAS can be diminished or blocked by several different classes of drugs (central sympatholytics, β-blockers, renin inhibitors, ACE inhibitors or ARBs); what is most important is how effectively the overall impact of angiotensin II is blunted. A second new concept is that the complementary actions of RAS blockers and calcium-channel blockers are best explained on the basis of diminished intracellular calcium availability in excitable tissue (sympathetic neurons and vascular smooth muscle cells) via parallel actions that reduce angiotensin II type-1 receptor stimulation and L-channel-mediated calcium flux. Aliskiren is the first of the direct renin inhibitors, the newest subclass of RAS blockers. In both short- and long-term studies, aliskiren has been shown to be similar in efficacy and tolerability compared with other RAS blockers, with the added benefit that its effects persist longer. Outcome studies with aliskiren are currently underway.

Keywords::

• calcium-channel blockers
• dual therapy
• hypertension
• renin–angiotensin system

Acknowledgements

The authors wish to thank Kanaka Sridharan, Novartis Pharmaceuticals, for assistance in reference searches.

Financial & competing interests disclosure

The authors wrote the manuscript in its entirety. They received support from Novartis Pharmaceuticals for preparation of the manuscript but retained all editorial authority over the content. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.