Monday, November 10, 2008


The American Heart Association is currently holding her annual scientific meeting (2008) in New Orleans. One of the landmark trials was presented yesterday, at the start of the meeting. Jupiter stands for " Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin". The investigators, under PI Dr Paul Ridker, studied 17,800 patients with elevated hs-CRP, but normal LDL-C. It was a placebo control, double blind trial, using MACCE events as their end point. The trials was scheduled for 4 years, but was prematurely terminated at 1.9 years, because the steering committee felt that it was improper to continue, seeing the huge benefit. There was a 44% reduction in events, in patients taking rosuvastatin 20mg.
This finding will certainly influence clinical practice.
There are a few interesting points about this study. Firstly, it showed me that MACCE events reduction with the use of statins maybe due to it's ability to lower hs-CRP, rather than LDL-C, or a combination of both. The old understanding that statins lower LDL-C and so clinical MACCE may have to be re-thought about. Secondly, better than the previous trials, where there was little benefit in women ( for primary prevention, I mean ), this trial showed that rosuvastatin, also work well in women, and hispanics. Thirdly, I was very surprise that there could be so much bebefit in 1.9years ( less than 2 years ). I always thought that ultrasound changes ( IVUS and CIMT changes) can occur in 18 months, but clinical events may take 4-5 years. This study, showed that when you reduce inflammation ( reduction in hs-CRP ), you can reduce events in 1.9 years, probably re-fuelling the old theory that infection may have something to do with this hs-CRP rise.
But alast, all is not so easy. Measurement of hs-CRP is no easy task. hs-CRP is so sensitive that standardisation is difficult and we have seen studies where hs-CRP results vary so widely, that made it's measurement practically useless. Our laboratories here do offer hs-CRP, but it is so sensitive that we have seen highs when we expect lows and lows when we expect highs that I have become skepical about the measurements by our labs. Dr Ridker happen to work in Boston, and his lab is a reference lab for hs-CRP measurement. He is one of the few labs where hs-CRP measurements are said to be reliable and consistent.
What is the impact? Well, I am certain that with this trial results, Astra-Zeneca will be pushing for rosuvastatin 20mg to be use as primary prevention. Maybe they would wish to revive the strategy to allow them to sell rosuvastatin ( over-the-counter ) OTC, for use as primary prevention agent. This would bring a big headache for healthcare administrators. Firstly, the issue of side efects when use in a large healthy population. Secondly, the issue of cost. Can you imaging how much it will expand the healthcare budget? That will make the cake smaller for other treatment modalities.
I must also add another word of caution. Rosuvastatin was the agent, when it was first launched, that had some deaths and cases of myolysis and renal failure, particularly in doses higher than 20mg. There were also reports out of Singapore that Asians may not be able to tolerate rosuvastatin 40mg and our dose requirement may be half that of Caucasians.
Well, they did not call rosuvastatin a super-statin for nothing.

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