Friday, May 25, 2007


We have reported earlier of a promising new anti-hypertensive agent that works by blocking the effect of Renin, a hormone secreted by the JG apparatus in the kidneys. Renin, of course is the  enzyme at the initiating point of the RAAS and is seen by some as the starting point for the hypertension cascade. When Novartis first annouced the "discovery " of aliskerin, many (ourselves included) saw the hope that there is a new agent to help in the war against hypertension. Remember, this was a proof of concept. But when the results of the aliskerin trials were announced, we found that while aliskerin is effective, it is a rather weak anti-hypertensive agent and certainly not better then the currently available ACE-I or ARBs.

The May issue of the American Journal of Hypertension, carried an editorial by Dr John Laragh with co-author Dr Jean Sealey (the wife), that decries the effectiveness of aliskerin. Dr Laragh raises the point that aliskerin is weak and what's worse, it raises plasma Renin (one can understand that when you block Renin activity, the negative feedback loop will physiologically raise the level of Renin). Dr Laragh cautions that the rise in Renin level could potentially be hypertension provoking (remember that renin initiates the RAA system). Alas that seems a rather timely reminder of a newly discovered compound.

It would appear that this editorial has brought to light an ongoing  "physician war" between Dr Laragh and his detractors, led by Dr Matthew Weir. When asked to comment on Dr Laragh's editorial, Dr Weir said things to the effect that if Dr Laragh had send his comments to any other hypertension journal, it would never have been published. It is worth noting that Dr Laragh is the chief editor of the Americn Journal of Hypertension. It is also worth nothing that Dr Weir is the author of many articles supporting the use of Aliskerin. Of course these two have tussle, we are told, previously, at the American Society of Hypertension (ASH) meeting, resulting in Dr Laragh becoming an almost "persona non grata" (We could almost boldly he say he got kicked in the ASH).

One must not forget that Dr Laragh comes with high credentials, being the discoverer of the effect of Renin in hypertension, in the early seventies. He is in fact Mr Renin. He used beta-blockers as an anti-renin agent. He stands important because at that time, hypertension was thought to be a central (CNS) activated disease. The brain was then thought to be the seat of hypertension. With the work of Dr Laragh, the focus shifted to the kidneys, Renin and the RAA system. So he is no small fry. This on-going war in the journals is rather unhealthy, although it does provide us a glimpse into how  "big academics" can behave.

On the positive note, we are grateful that the controversy have cause us (as on-lookers) to see that a few things we can agree on. Firstly, that Aliskerin is a rather weak agent and may have limited role to play, except as an alternative agent or in combination with another agent, in the treatment of hypertension. Secondly, we also learnt that Aliskerin can raise Plasma Renin level. What effect this will have, will require much more work, and more clinical trial results. We need to make sure that it is safe. Raising plasma Renin can be potentially harmful. But let us see the evidence. And thirdly, and perhaps the most important, that senior, matured, academics, sitting on their hobby horse  and squabbling like little children, all in the name of academia. Plus the fact that this blog get the opportunity to mention two doctors fighting over ASH. Look out for more coming soon.

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