OHHHH NO NOT THIS ON STATINS!!!

[storm]

Ohhh no !!
http://news.bbc.co.uk/2/hi/health/7971414.stm

[godsilove]

Ohhh no !!
http://news.bbc.co.uk/2/hi/health/7971414.stm

Look on the bright side - if the effect is real and strong enough (and can be corroborated through a trial in patients at risk for DVT, not just through a post-hoc analysis of a trial) then it could replace drugs like warfarin which are far more toxic.

[ofonorow]

[J.Lilinoe]

The study appears in the New England Journal of Medicine.

Wonder who funded the study? Astra Zeneca? Perhaps that is why the serious side effects of taking Crestor were left out?

[godsilove]

The study appears in the New England Journal of Medicine.

Wonder who funded the study? Astra Zeneca? Perhaps that is why the serious side effects of taking Crestor were left out?

Which serious side effects were left out?

[J.Lilinoe]

Which serious side effects were left out?

Actually, the first question to answer is, who funded the study? Do you know?
My guess is that it was funded by Astra Zeneca and that is why the study "appears to be" so favorable toward the drug.

As to your question, which serious side effects were left out? I don't know. Do you? I think that a study using a drug that is listed as "The Most Dangerous Cholesterol-Lowering Statin Drug" should provide both sides of the story, don't you?

[godsilove]

Which serious side effects were left out?

Actually, the first question to answer is, who funded the study? Do you know?
My guess is that it was funded by Astra Zeneca and that is why the study "appears to be" so favorable toward the drug.

Since this is based on data from the JUPITER trial, you're correct that it was funded by AstraZeneca, but your next point does not follow. Plenty of industry-sponsored studies are NOT favorable towards the study drug, so you need to have a more compelling reason as to why this particular study only "appears to be" favorable.

As to your question, which serious side effects were left out? I don't know. Do you?

That's a loaded question. I only asked because you seemed to know of something that the authors failed to mention in their paper.

I think that a study using a drug that is listed as "The Most Dangerous Cholesterol-Lowering Statin Drug" should provide both sides of the story, don't you?

The most dangerous cholesterol-lowering statin drug is Baycol (cerivastatin), and it was withdrawn from the market.

As for both sides of the story, you're asking a loaded question again. What do you think was left out from the study? The investigators are required to provide information on the side effects experienced during the trial period, and these were provided in the original publication. Rhabomyolysis and myopathy are usually the most serious adverse events associated with statin use - these occured in <0.1% and 0.1% of patients in the treatment arm (8,901 patients), respectively. Newly diagnosed diabetes was reported in 3% and 2.4% of patients on Crestor and placebo, respectively. The median follow-up time in the trial was just under two years, so obviously the paper cannot report on potential side effects associated with longer term use.

[J.Lilinoe]

The median follow-up time in the trial was just under two years, so obviously the paper cannot report on potential side effects associated with longer term use.

And since the study only lasted less than 2 years, and since it is assumed that patients will take the drug long term (more than 2 years) then the study is only good for short term use and is actually pretty useless for long term use IMO.

[J.Lilinoe]

Furthermore, I think we should expect studies using Crestor to always last less than 2 years because anything longer would actually reveal all those nasty side effects. But these studies should never be used to justify long term use IMO.

[godsilove]

The median follow-up time in the trial was just under two years, so obviously the paper cannot report on potential side effects associated with longer term use.

And since the study only lasted less than 2 years, and since it is assumed that patients will take the drug long term (more than 2 years) then the study is only good for short term use and is actually pretty useless for long term use IMO.

Not useless, just unproven in terms of long-term safety and efficacy in this particular cohort of patients (i.e. low LDL, high CRP)...

But this is not a case of serious side effects being left out, as you suggested. Of course there are various factors to be taken into consideration, and legitimate concerns about prescribing Crestor for primary prevention in this patient pool. Questions about long term safety with Crestor still exist, although other statins which have been on the market longer do have a favorable safety record. A more important issue IMO is the cost-benefit ratio, given that Crestor is still patented and the number of patients that would have to be treated to avoid one myocardial infarction is quite high.

Furthermore, I think we should expect studies using Crestor to always last less than 2 years because anything longer would actually reveal all those nasty side effects. But these studies should never be used to justify long term use IMO.

It would be fairer to say that any randomized, placebo-controlled trials with Crestor will probably be only a few years long. This is partly due to the high cost of running such trials, but it also has to do with the ethical issue of having patients on placebo over a long period of time. The reason the JUPITER trial was stopped early was because the independent data and safety monitoring board decided that there was a clear benefit associated with statin therapy, and that patients in the placebo arm should be offered the treatment. This does not mean that long-term observational studies of Crestor will not occur (we already have observational studies with the other statins that show a good track record over the long term).

But again, what "nasty side effects" occur with Crestor over the long term, and what is the incidence?

[ofonorow]

safety monitoring board decided that there was a clear benefit associated with statin therapy,

"clear benefit" ??? You have seen the graph, especially lower graph, right? http://vitamincfoundation.org/images/graph.png

[godsilove]

safety monitoring board decided that there was a clear benefit associated with statin therapy,

"clear benefit" ??? You have seen the graph, especially lower graph, right? http://vitamincfoundation.org/images/graph.png

The decrease in absolute risk was low as this was a fairly low risk group of patients to begin with. As I said earlier, the number needed to treat to avoid a single death is quite high - nonetheless, there was still a statistically significant decrease in mortality, which the DSMB decided was enough to terminate the trial and allow patients in the placebo group to receive treatment. If the trial continued for the full four years, that would have meant a disproportionate amount of deaths in the placebo arm (it is worth noting that although the median duration was 1.9, there were patients who had been enrolled for four years in both arms, and the benefits were also seen in amongst these patients). Even if the absolute risk reduction of cardiovascular events was low (1.2%), that is still 10 avoidable events out of every thousand patients in the placebo arm.

I don't think the take-home message from the JUPITER trial should be that all patients such as those used in the trial should be prescribed potent statins like Crestor. I think the importance of the findings reinforce the notion that high hsCRP levels should also be treated as a risk factor independent of LDL cholesterol, and should be taken into consideration when evaluating a patient's risk profile. For a patient at low risk, a 44% reduction in risk of having a cardiovascular event is perhaps not clinically meaningful; on the other hand, a patient with a family history of cardiovascular disease, high blood lipids, high hsCRP, and obesity would probably derive a more substantial benefit from statin therapy. At the end of the day, results from clinical trials should always be used judiciously and in a personalized approach.

[J.Lilinoe]

The reason the JUPITER trial was stopped early was because the independent data and safety monitoring board decided that there was a clear benefit associated with statin therapy, and that patients in the placebo arm should be offered the treatment.

That's the flimsy reason that the drug companies love to use in order to fool people and keep them from knowing that if the study were to last a life time, the benefits would be dwarfed by all those harmful, nasty side effects.

[bbtri]

http://www.spacedoc.net/

[godsilove]

The reason the JUPITER trial was stopped early was because the independent data and safety monitoring board decided that there was a clear benefit associated with statin therapy, and that patients in the placebo arm should be offered the treatment.

That's the flimsy reason that the drug companies love to use in order to fool people and keep them from knowing that if the study were to last a life time, the benefits would be dwarfed by all those harmful, nasty side effects.

The study was meant to last four years - even if it were allowed to go on till then, it is unlikely to have been very informative in terms of long term side effects. Bear in mind that although the median duration in the trial was 1.9 years, there were a group of patients who had been enrolled for much longer and the small but significant benefits in mortality and morbidity were visible in these patients as well. It's both too expensive and unethical to have a randomized trial that would last for ten years or so. The next best option is observational cohort studies and ongoing phase IV studies.

But I'm just wondering why you're so sure that benefits would be dwarfed by "harmful, nasty side effects" in the long run. Have you secretly conducted your own study?