What's this about?
The FDA is reviewing the results of the JUPITER trial. I blogged about the results of the Jupiter trial a year ago. Basically this study looked at over 17,000 patients with relatively normal cholesterol levels, but an elevated CRP, which is a marker of inflammation and has been associated with elevated risk for heart attack and stroke. The study was planned for 4 years, but stopped just short of 2 years because they found a substantial benefit for patients taking Crestor. Crestor reduced the risk of heart related deaths, heart attacks, and other serious cardiac complications by 44%. These results are pretty impressive.
What's the FDA have to do with this?
Why is the FDA weighing in on a year old study for a drug that is already on the market? Because Astra Zeneca, the maker of Crestor, is asking the FDA to give Crestor and indication to use Crestor in patients with normal LDL's but elevated CRP's. Currently, all statin medications are only indicated to treat high cholesterol in order to prevent heart attacks and strokes, not to actually prevent heart attacks and strokes irrespective of cholesterol.
I have previously discussed the meaning of "indication" in a post called "An indication for change." Basically, even though Crestor has been proven to prevent heart attacks in patients with elevated CRP and normal cholesterol, the company can not share this information with doctors or advertise this information with patients until it gets the indication. You may notice that a recent Crestor commercial shows a woman over time who states that while she was building a family/career, atherosclerotic plaques were building up in her arterties. The reason this is a focus of the commercial is because Crestor recently got an indication to prevent the progression of atherosclerosis. Since it is the only statin with this indication, the company likely wants to use this as a competitive edge over other statins. It it gets the CRP indication, it will likely use this in advertising messages to doctors and patients.
What does this mean for me?
Actually, the study results have been out for over a year, so this is not really anything new. However, if the FDA does go forward with the panel's recommendations, you will likely hear more about testing for CRP, and your doctor may even recommend this test.
Should I use a statin to treat an elevated CRP?
The jury is still out. This may change though, as the Adult Treatment Panel IV (ATP4), a NIH sponsored group, will soon make its new cholesterol treatment recommendations. They will have to address the CRP issue. The US Preventative Health Task Force (the same government group that recently told younger women to stop getting mammograms) recently stated that they felt there was insufficient evidence to recommend this. This is true, because though there are numerous studies associating CRP to cardiovascular risk, only the JUPITER study shows that treatment works. That being said, the JUPITER study is a very large, randomized trial with substantial differences between treatment and placebo groups, so it should not be ignored. If you don't want to wait until the APT4 weighs in, I would discuss this with your physician. If you are very worried about heart attacks and strokes (possibly a strong family history), but have a normal cholesterol, treating an elevated CRP might be a reasonable option for you.
What do the nay-sayers say?
There are many that will come out against this, regardless of what the ATP4 decides. In addition to stating that there isn't enough data they will say:
- "The patients in the JUPITER study taking Crestor developed diabetes". This is true, but most of the patients in the study were at risk of developing diabetes. Even though there were statistically a few more patients taking Crestor that developed diabetes, it is very unlikely that this was real, and other markers of diabetes were the same
- "You are taking medications that have side effects." It is true that any medication has side effects. However, one interesting thing that came out of the JUPITER study was that there were really no difference in side effects between the placebo group and Crestor group. Given that the 20mg dose used in the study was a relatively high dose, this is pretty impressive. Groups like Public Citizen warned of the dangers of Crestor, but this drug has proven to be quite safe.
- "The patients in JUPITER did not exactly have normal cholesterol levels, and their risk was high." This is a valid criticism. In order to really prove that treating elevated CRP levels with a statin prevents heart attacks, you would need to find patients with an otherwise low risk for heart disease (i.e. not pre-diabetic) and an ldl cholesterol below 100. However, the patients in JUPITER were very representative of the normal population of patients (60% of the country is overweight or obese and many a pre-diabetic) that would not usually get a statin medication.
Do I have to take Crestor to treat an elevated CRP?
This is actually a very important question. Currently, simivastatin is a generic cholesterol medicine and much cheaper then Crestor. Though simvastatin has not shown it can reduce heart attacks by lowering CRP, many physicians will assume a "class effect" and believe that all statins will do this. The problem is that a dose of 20mg of Crestor was used in the JUPITER study, and no amount of simvastatin will lower CRP or LDL by that much. In most studies that have measured CRP lowering with statins, it is the very potent statins that seem to work. In addition, though all statins have shown prevention of heart attacks and strokes, only the more potent statins (Lipitor and Crestor) at high doses have shown to prevent the progresssion and even shown reversal of plaque build up. This will become an even more important issue when Lipitor goes generic.
Bottom Line:The FDA will very likely approve Crestor for treating elevated CRP levels, and you will hear about this in the media and in advertisements. Though based on one study, the results are compelling enough to discuss this with your doctor and consider CRP testing.
3 comments:
Large number of people screened in Jupiter to get the their ~20K enrollees. Evidence may be rx'ing people with high CRPs of benefit, but is there positive outcome if significant numbers of low risk people get tested, and on net net, will overall benefit (and value) result?
For intermediate risk folks, would you concede that treatment intensification still might be preferred, jury still out on CRP? (as per earlier 09 USPTF in AIM)
could you please start using absolute risk reduction and NNT instead of relative risk reduction when talking about study results? (or at least present both)
44% relative risk sounds great, but it's always nice to know the absolute differences to put things in perspective.
Brad F, not sure I entirely understand your question. It is true that many would need to be screened, but the risk of screening (including cost) is pretty minimal, so even one adverse event prevented is probably worth it.
Anyonymous,
You are correct that absolute risk reduction and NNT is a better measure and I will try to use more in the future. The problem is that they are not always easy to figure out immediately. For the JUPITER study, the results are reported in rates and the primary outcome was a large composite outcome. The ARR was 1.2% which sounds small, but the NNT is 82, which means that 82 patients would need to be treated with Crestor for 2 years to prevent one adverse event (stroke, MI, death, hospitalization). This number is pretty reasonable. However, it is important to understand that the study was stopped early. Had they continued for the full 3 years, the ARR would have likely gone up and the NNT would have gone down.
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