Wednesday, 12 November 2008

Cardiologists circumspect on stellar JUPITER results

The publication this week in New England Journal of Medicine of the JUPITER trial - which found that the statin rosuvastatin reduces the risk of heart attack and other cardiovascular events in people with normal cholesterol levels - has cause quite a stir. The likes of the BBC and the Daily Mail squealed that statins should be prescribed to all healthy adults, but what did the study actually look at, and what do doctors think of the findings?

In patients with raised cholesterol levels, treatment with statins reduces the risk of cardiovascular events such as heart attack and stroke; however, nearly half of all first cardiovascular events occur in people whose cholesterol levels are below current thresholds for pharmacological therapy. The JUPITER trial investigated the benefits of treatment with rosuvastatin (also known as crestor) in 17,802 patients over 50 years of age who had normal blood levels of low density lipoprotein (LDL) cholesterol ('bad' cholesterol), but elevated levels of another marker of heart disease called C-reactive protein (CRP).

Compared with a placebo, statin treatment reduced the levels of both LDL cholesterol and CRP by considerable amounts (50% and 37%, respectively), and also almost halved the likelihood of a major cardiovascular event such as a heart attack or stroke. When the results were broken down, it was found that the risk specifically of heart attack was reduced by 54% and the risk of fatal or nonfatal stroke decreased by 48%.

CRP levels are not usually measured in people at risk of heart disease, yet statin treatment had a remarkable effect in people who were otherwise apparently healthy but had elevated levels of this marker. Doctors are now been asking whether measurement of CRP levels should be undertaken in all people at risk of heart disease, and whether statins should be prescribed as a preventative measure to a wider range of people, regardless of whether their cholesterol levels indicate that they should receive such treatment.

In an editorial in the same issue of New England Journal of Medicine, Mark A Hlatky from Stanford University School of Medicine in California goes through the trial with a fine tooth comb to decide whether or not doctors should change how they prescribe statins.

He notes that "JUPITER was a trial of statin therapy, not high-sensitivity CRP testing", and opines that "the evidence still favors [a] selective strategy for measuring high-sensitivity C-reactive protein, not routine measurement". Dr Hlatky also points out that the trial was only 2 years long, so could not assess the effects of long-term statin treatment, and that the cost of rosuvastatin is much higher than that of generic statins, so the benefits of broader prescription of rosuvastatin treatment need to be weighed up against these factors.

You don't have to just take Dr Hlatky's word though. New England Journal of Medicine are hosting an online Clinical Directions poll to find out directly from doctors whether they are likely to change how they practice on the basis of the JUPITER results.

So far over 1,500 doctors and medical professionals have voted in the poll, and only 53% believe that the approach to laboratory screening and therapeutic use of statins in apparently healthy adults should be changed. The comments on the poll are just as cautious - Greg Rice of Libby, Montana says "Certainly what this study clearly shows most is that there is a large cohort of high risk patients we are missing. However, simply giving them a statin is not a very cost effective way to reduce the risk of coronary disease", whereas Timur Timurkaynak of Ankara, Turkey states "I really wonder what have we learned from jupiter trial that we don't know before".

So it seems that the jury is going to being deliberating for some time as to whether apparently healthy people should have their CRP levels measured and should receive statins. The JUPITER trial seems to have thrown up more questions than it has answered, and it is clear that more research is needed before statins start getting dished out willy nilly.
  • Nature News has a good run down of the JUPITER study and whether you should be heading straight to your doctor for preventative statin treatment
Ridker PM et al. (2008). Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein New England Journal of Medicine DOI: 10.1056/NEJMoa0807646


gio said...

It does not make sense to start prescribing statins to people with higher levels of C-reactive proteins simply because it has not been shown that something simpler and cheaper -- taking low-dose aspirin, for instance -- would help reduce generalized inflammation and therefore impact levels of C-reactive protein.

And even so, it has not been showed that levels of C-reactive proteins are good predictors of cardiovascular disease, although the study suggests so.

Adding to that, there's the fact that the study was commissioned to basically support the use of statins in otherwise healthy people, which would surely benefit AstraZeneca greatly.

So I am not surprised that people are cautious. I am, however, surprised by the fact that 47% of those 1,500 physicians are thinking that what they are doing should be changed right now....

Helen Jaques said...

Yeah, one of the issues with this study is that it wasn't designed to test the clinical utility of measuring CRP levels. As the NEJM editorial points out: "the study provides only limited and indirect information about the role of high-sensitivity C-reactive protein testing in clinical management, since the trial did not compare subjects with and those without high-sensitivity C-reactive protein measurements".

And you're right, it is pretty important that the makers of rosuvastatin sponsored a trial that had such positive results...

Helen Jaques said...

The PLoS Medicine blog has an interesting post about the NEJM online poll on whether doctors will change their practice on the basis of the results of the JUPITER trial.