Sunday, August 29, 2010


Novartis was quick to announce that on Friday, the FDA had approved their aliskerin / amlodipine combo pill for the management of hypertension.
Aliskerin is a new group of BP lowering pill that is essentially anti-renin or renin lowering. As we are all aware, BP control has much to do with control of the renin- angiotensin-aldosterone system ( or commonly called the RAS system ). Hypertension may essentially be a derangement of the RAS system, The RAS is a system given to us by God to maintain and adjust our BP as we face the day to day stress and changes in fluid volume and cardiac output. BP equals cardiac output x total peripheral resistance. Both cardiac output and peripheral resistance is dictated by the RAS. When the RAS system goes dysfunctional, the BP is maintained abnormally high all the time ( a situation called hypertension ). In fact the earlier seminal work of Dr John Laragh, in the 70s, was to classify hypertension in 3 forms, the low renin group, the normal renin group and the high renin group. Although this classification sounded very neat and tidy, it was difficult to apply clinically, as the measurement of renin was very involved, complicated and not clinically practical. Thereafter, in the 90s, the concept largely fell out of favour and pharmas began to developed drugs that attacked the mid-portion ( ACE-I ) of the RAS and also the end receptor of the RAS ( the ARBs ).
The trouble that we face with blockers of the RAS system, is that chronic blockade of any part of the RAS, gives rise to escapes from the RAS. Acute blockade works very well, but chronic blockade, allows the system to find alternative pathways of compensation. The RAS is a survival maintaining system. It cannot be blocked forever. It will adapt, escape, so that fluid volumes and cardiac output can be maintained, for survival of the human.
Novartis is leading the way to try and block the beginning of the RAS, with the discovery of " aliskerin ". I believe that aliskerin is the first of many such drugs. It has been shown to be effective and safe, but I found the data on it rather weak. The drug is also rather weak, in terms of BP control. Escape routes from the renin blockade sets in quite quickly. And aliskerin is expensive. Therefore aliskerin alone may not be cost effective.
Looks like Novartis has taken note of this and have combined aliskerin with the more established CCB ( calcium channel blocker ), in a single combo pill, just approved by FDA yesterday. This certainly enhances the efficacy of aliskerin in BP control.
Looks like combo pills for BP control is the way to go, and Novartis is just pushing the case further. They now have a ARB + diuretic combo, ARB + CCB combo, now anti-renin + CCB combo, and also a ARB + CCB + diuretic combo.
The war against hypertension carries on at a new level. Novartis has just raised the bar.
I must say that I very much prefer life style modification ( lose weight ), green veges and fruits ( DASH diet ), regular exercise and single, or at most double pill combo. I find this very cost effective. The solution for a chronic lifestyle disease, must be chronic lifestyle modification. Hypertension is a chronic lifestyle disease.

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