Thursday saw the delivery of a new Novartis drug: Tekturna (aliskiren). None of us had any idea what it was for, so we looked it up on Facts and Comparisons, and there was next to no information whatsoever, except that it is a “direct renin inhibitor” — whatever that meant.
Now that I’m home on a non-firewalled Internet connection, I can actually get real drug information. (How sad is it that I can’t do this at the pharmacy?) Aliskiren:
Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known
I’m sure you could play games targeting specific points and pathways in the renin-angiotensin-aldosterone system until the cows come home, but how many of them will be meaningful? Medscape has an article comparing, contrasting, and using Diovan and Tekturna in parallel:
Do we need Tekturna? Would not an ARB plus a diuretic do a better job? There are benefits to combining an ACEi with an ARB, that are fairly well understood. Is Tekturna going to create some sort of super trifecta?
I’m thinking not. Combining an ACEi with an ARB does a couple of things. First off, ACE inhibitors only stop the conversion of angiotensin I to angiotensin II. Blocking the pathway there does nothing to stop any non-specific binding to the angiotensin II receptor sites. ARBs block much of this non-specific binding because the receptor sites themselves are blocked. However ACEis also block the breakdown of bradkinin (which is broken down by ACE) which leads to greater vasodilation, which is why ACEis and ARBs are usually similar is study results. Bradykinins, of course, are a double-edged sword: they may contribute to vasodilation, but they are also responsible for the dry cough and angioedema associated with ACEis.
I don’t see how aliskiren is going to add to this. Is there component to the RAAS that I’m not thinking of? Is it not better to attack a problem from many different angles instead of hitting the same pathway three different ways?