Crestor, by Jove... or Not

That's the 56 percent reduction that is being trumpeted. That means I'd have to treat a hundred or more people with Crestor for a year to spare one of them a cardiovascular event that they would not have otherwise had. I'd have to treat several hundred for a year to spare one a heart attack, and perhaps hundreds more to spare one a stroke. I am unwilling to even suggest a life-saving benefit.

So the reduction of 56 percent may be hard to ignore, but it calls for reflection rather than prescribing zeal. It is a reduction in a very small outcome to an even smaller outcome. Consider these two questions:

Are you convinced this small effect is real, that it will reproduce if one were to repeat the JUPITER trial?

I am not. I am reflexively skeptical of effects of this magnitude. My main reason relates to the nature of the randomized controlled trials we rely on for evidence. There are many factors vying to seal a well person's cardiovascular fate.

For example, there are the so-called cardiovascular risk factors such obesity and tobacco abuse. By assigning volunteers randomly to Crestor or placebo, one hopes that the number of smokers and obese folks are equal in the two groups.

When the JUPITER investigators checked, indeed such measurable risk factors were distributed 50-50. One has to have faith that the factors that cannot be safely measured (such as the degree to which the blood vessels are diseased) also distribute 50-50. And one has to have faith that the factors that JUPITER was designed to ignore distribute 50-50.

Socioeconomic status, job security, education level are even more important risk factors that are independent of those measured and likely to vary widely across the research sites in these 26 countries. Slight imbalances between the Crestor and placebo groups could result in effects of the magnitude touted by JUPITER.

I never leap to act on the basis of such small effects. It's why this year if you feed your family margarine, you're not a caring person and last year it was butter that was bad for you.

If you're convinced these small effects are real, are they meaningful to you?

Are you willing to swallow Crestor every day for two years in the hopes you're the one in hundreds who just might be spared a non-fatal heart attack? Does it bother you that more of the volunteers on Crestor were diagnosed with diabetes?

This possible association aside, there is nothing to suggest that the volunteers for JUPITER were harmed in the two years. But that does not mean the drug is risk-free. Does it bother you that the occasional person on Crestor develops a muscle disease, or that some have liver or kidney irritation?

I am not tormented by such uncertainties as I doubt the small effects are real and therefore have no interest in taking Crestor. You and your prescribing physician should take pause, at the very least.

Small Effect, Big Benefit? Debate Continues

However, the JUPITER investigators and AstraZeneca do not share my concerns. Rather they take refuge in several of the tenets of contemporary small-effect epidemiology. They believe that these small effects are real.

Furthermore, they believe that the small effects recognized in the first two years are likely to prove cumulative and therefore grow as the years pass. It's this belief that triggered the halting of the trial.

Page
  • 1
  • |
  • 2
  • |
  • 3
Join the Discussion
You are using an outdated version of Internet Explorer. Please click here to upgrade your browser in order to comment.
blog comments powered by Disqus
 
You Might Also Like...