This is definitely a ground breaking study and will change my practice. I always find it interesting to hear the comments about cost and NNT, but patients/families don't care about this when it comes to life or death. We are talking about the #1 killer for which many patients first sign of disease is death. I would guess that many who are playing devils advocate, will be the first to test themselves for CRP.

In regards to some of the other comments made here, I have no concern for the study being stopped early. It was a placebo controlled trial that would have been unethical to continue when you have 50% reduction in events. The study was powered to show a 25% reduction at 5 years and with this dramatic benefit, the monitoring board had no other choice. Regarding the NNT/absolute risk reduction, I was actually very impressed considering this was a healthy population that is not currently being treated. If I can reduce my patients risk of dying from 2% to 1%, that is nothing to turn up our noses at especially in a "relatively healthy population". In regards to generics, the data shows us that the vast majority of patients do not reach their goals when treated with generic statin medications and the risk of side effects to our patients is greatly increased when using the much higher doses necessary to try an achieve targets. Jupiter provides further evidence to the LDL hypothesis that lower is better.

One possible clue to suggest that the observed risk reduction was indeed due to CRP reduction could be the consistent benefit observed in the "10% or lower" absolute risk subgroup. According to the authors, those patients had no metabolic syndrome. In regard to adverse effects, I believe that cancer could be an important concern in view of a recent meta-analysis published in JACC last year, where the authors found a disturbing inverse correlation between absolute levels of LDLc achieved and newly diagnosed cancer. Even though those findings can only be vieved as hypothesis - generating, it seems obvious that a 1,9-year period may be too short to reassure us about the safety of keeping such low LDL levels by pharmacologic means for several years. 

Is it really a ground breaking study or is it construed to be. The ASCOT study was much more significant in the fact that we see more patients who are hypertensives and still only treated with antihypertensives.

The dose of Rosuvastatin ( 20mg ) is very significant. Why was 20mg used instead of 10mg? If 10mg is used which is logical for patients without elevated LDL, would it still benefit the patients?

In the ASCOT only 10mg of Atorvastatin was used. In the CARDS only 10mg of Atorvastatin was used for the diabetics!

It would be really interesting to know the view points on the above!

Good study, but better promo for CRP and Crestor. Nonspecific CRP results add clarity to treatment decisions for cholesterol, because of the weakness of LDL in predicting CV risk and as you pointed out Dr Topol, the prevalence of visceral adiposity and smoking in the study population. I think it would be foolish to initiate statin therapy based on LDL (or CRP ) alone. The validity of prediction rests on the statistical base with large N. In the examining room where N=1, for 95% of the encounters, there is a breakdown and LDL (and CRP?) risk is properly estimated in only 1 of 3, with the remainder under or overestimated. Given the complexity of risk factors for atherosclerosis and the fact that we measure them only in one point in time and have little clinical access to measures of oxidative stress that modify functionality of lipid particles or their metabolism, I bail out of the traditional approach. CIMT has served my patients well in the past 11 years (William B will advocate CAC). CIMT serves as the painless biopsy before starting "chemotherapy".

Dear Dr Topol, I feel we would certainly change our practice with Jupiter findings. Would you be available for a CME program in March2009 for Indian Drs on Statin therapy? If yes, then pls confirm the dates during which you can travel.

I just could not leave "real" comments alone.  Are you kidding me?  Where in your practice has generic simva had a consistent 50% ldl lowering at ANY dose?  WOW.  Time to hang up the shingle skippy.  Science has passed you by - LONG ago. And where in this study was the goal to "get these patients to goal"?  Have you read the study? It is available online.  Go find it. Read it. Change your practice, save some lifes.

WOW.

 

 

 

I agree with B. Shah. A 2 x 2 factorial design as he proposes would have lead to more useful information.  The fact that only persons with a hs-CRP > 2.0 mg/L were included introduces a potential bias in assessing the results. A similar group with LDL <130 mg/dL & hs-CRP < 2.0 mg/L should have been used as a comparator to be able to correctly interpret the results. As has been pointed out the sample group was not truly a "healthy" cohort (40% with MS!!!). These are additional risk factors that could be acting as confounders. 

I have been testing some truly "normal" persons for hs-CRP and it is very difficult to find a really healthy person with high hs-CRP. I think a truly normal person with a high hs-CRP is an infrequent finding. The question is then: does the JUPITER population represent a real life scenario? I have my doubts and therefore I feel that before we get excited and change guideliness, better information is required. Till then, I would recommend caution in the application of the JUPITER information. "Not everything that glitters is gold" 

I would really like to know more about the patient population, specifically their risk factor profile. I would assume this is available, I just haven't seen it yet. The results would be less surprising if these "healthy" patients actually had lots of major risk factors.

 

rlb

Our recent election was decided by 52 to 47 and it seems that statin therapy will be endorsed by similar numbers. For the naysayers all I have to say is if your LDL is 135 do not treat it until after your initial coronary event. JUPITER shows that our "non elevated" cholesterol levels are too high. Clinical cardiovascular disease manifests in more than 50% of the population. In that sense universal treatment with a statin makes more sense than universal vaccination against tetanus. Questions of cost, generics etc apply but I do not expect Astra Zeneca to promote generic simvastatin. When they test the "polypill' in England we will have final proof if this approach is correct. Until then I prefer to be proactive.

If we look deep down at this study and several of Crestors previous studies...these are "Marketing" driven studies and not true "Scientifically" driven studies...please...screen 90000 patients so you can get exactly the type of patient that you can show benefit, then compare your statin to placebo...the 44% reduction in the Crestor arm was 142 patients versus 251 in the placebo arm...yes, a reduction of 44%...out of 17000 patients!!!...once again...a "marketing" driven study...which the media beautifully picked up and most people are touting as extraordinary...but why?...why?...because Crestor has to create a bigger Cholesterol market pie in order to grow more market share...why?...when Lipitor goes generic in 2011...the Cholesterol pie will take a big hit...unless you are Crestor and you have prepared some clever marketing studies over the past years to show that you are different than Lipitor and you are worth the cost beyond generics!...once again..."Marketing" driven study taken right out of the Pfizer playbook!!!

Although it is true that 40% in the trial had the metabolic syndrome (MS), the subgroup analyses reveal that Rosuvastatin still had impressive benefit in patients without MS, as well as in patients without ATP-III risk factors and those with Framingham risk scores < 10%. This suggests that even low risk patients with elevated CRP levels will benefit from statin therapy. (I agree that a 2x2 design would have been more helpful, but we have the data we have).

For this reason, I believe that this study will eventually open up routine testing of CRP in all patients over a certain age and statin treatment in patients whose levels are high. This will take time to develop as executive committee meetings need to occur. But I think the evidence here is clear.

Good points, Steven. You are shedding light on the fact that CRP is a nonspecific marker and that one needs to consider the larger picture first. I agree with this. There is no replacement for good clinician judgement with individual patients. It is also one of the joys of medicine and what likely got us into this in the first place.

But there is evidence that patients with diseases processes suchs as rheumatoid arthritis, HIV, etc that cause widespread inflammation and elevated CRPs are predisposed to early atherosclerotic disease. One question I have is would treating the underlying process first, ie with the standard armamentarium (DMARDS, methotrexate for RA, HAART for HIV) before prescribing statins decreases their risk of CAD? I don't know if that's been answered and I think is a relevant question.

But I think you are right to say that if you treat the underlying process first and CRP improves to normal then there is no reason to give a statin in the absence of hyperlipidemia or preexisting CAD.

 

Impressive results with respect to relative risk reduction, but absolute risk reduction (ARR) is small.  However, the small ARR is not to be unexpected, given the relatively low risk primary prevention population evaluated.

I am not a believer in CRP as an independent risk factor that needs special attention, and do not think this trial changes that view, since we did not have a comparator group of similar clinical risk characteristics but with normal CRP.  

The conclusion that I draw from JUPITER is that CRESTOR is effective at CV risk reduction in a primary prevention setting.  This is consistent with my views on the utility of statins in primary prevention.  So CRESTOR may have a role to play here, but with the cost and small ARR, I will not be using it routinely in primary prevention.  I will tend to use statins somewhat more now in primary prevention, even though I already use them relatively aggressively in this setting, certainly for higher risk patients.  But I am not convinced that the results of JUPITER should be applied exclusively to patients with positive CRP, since this could still be an epiphenomenon.  And I do not argue with the results, and think that they can readily apply to patients with moderate atherthrombotic risk.

    

 Very imprressive study.

 Although the Absolute risk reduction was small... but it was a population of intemediate-to low risk in whom, probably none of us would do anything. So perhaps the study should make us to reconsider about it, measuring HS-CRP or something else...such us using a more accurate risk prediction model.

 Anyway, I think the study supports the hypothesis that hs-CRP is, no doubt, a risk marker, and probably, highly probably, a risk factor. I realize best study design to test whether CRP

Thanks to Dr. Avizohar for this unique perspective as one of the investigators.

I, too,  am troubled by the diabetes which has not been previously reported with a statin. And, as many of the prior comments reflect, most of the reduction in all cause mortality was related to less cancer deaths. That's not a bad thing, but not what would be expected.

It is terrific to see the varied and thoughtful processing of this data set and I appreciate all of those who take the time to write their comments.

 

Trials like Jupiter expand our knowledge in an important way but their incremental value for the well beeing of the patients is at best marginal. It has become increasingly difficult to find hypotheses that change the practise of medicine really significiantly (like thrombolysis, dPCI, betablockers in HF) so people test sort of virtual hypotheses.

Why don't we try to do better where benefits are obvious and proven rather than adding pills where they are higly unlikely to affect the course of the individual patient's life and possibly pose unknown risk? How many patients will be assigned to rosuvastatin because of randomly (i.e. falsely from this point of view) elevated CRP in the coming months/years? 

This is an interesting high cost population study that is difficult to translate into management of individual patient. Last but not least - with lower benefits , the risk/benefit ratio goes up.