The most frequently prescribed drug class in Canada may soon become much, much more popular.

AstraZeneca has filed an application with Health Canada to add a new indication for its drug rosuvastatin (Crestor). The application, filed late last year and still under review, asks that rosuvastatin be licensed for use in older patients with normal cholesterol levels but elevated high-sensitivity C-reactive protein (CRP). If approved, the new indication could potentially result in millions of Canadian patients being put on preventive statin therapy.

Whether or not AstraZeneca’s new application is approved, however, recent research makes it all but certain that statins are well on their way to far wider use in the years to come.

The new application is based on the giant JUPITER trial, the results of which were published in the New England Journal of Medicine in late 2008. The study showed that prescribing rosuvastatin to patients (men over 50, women over 60) with normal LDL cholesterol (< 130mg/dl) and elevated CRP (> 2mg/dl) reduced the risk of heart attack, stroke or other life-threatening vascular events by 47% compared to placebo, for an absolute risk reduction of around one fewer vascular event per hundred patients. Besides a small and questionably significant rise in diabetes rates, there were few serious side effects.

The results were big news. Using statins to reduce cardiovascular risk was already well established as primary prevention for patients with high LDL cholesterol, and as secondary prevention for cardiac patients with normal cholesterol. The JUPITER trial’s major accomplishment was to show that statin therapy is effective as primary prevention for some patients with normal cholesterol. The Canadian Cardiovascular Society, in the latest edition of its dyslipidemia guidelines, essentially endorsed JUPITER as a model for statin prescriptions.

As the JUPITER results seep into the medical consciousness, will physicians interpret its results as a green light to hand out statins far more frequently — regardless of Health Canada’s decision on AstraZeneca’s new application? In fact, this is already happening to some extent. One prominent Canadian cardiologist told Parkhurst Exchange that some FPs now prescribe statins almost universally and some cardiologists themselves take the samples that statin manufacturers send them — no matter their LDL or CRP levels.

Where will this trend lead us? In the U.K., statins were made available over the counter in 2004. With the recent positive data and a dramatic expansion of statin indications perhaps not far off, could Canada follow the British lead?

We asked two experts about these issues: Dr. Jacques Genest, one of the JUPITER investigators, a co-author of the CCS guidelines and head of cardiology at the McGill University Health Centre, and Dr. Gordon Guyatt, a McMaster University clinical epidemiologist responsible for coining the phrase “evidence-based medicine.”

Interview

Dr Jacques Genest

PE Are you concerned some doctors will prescribe statins to patients with normal cholesterol without measuring CRP?

JG If the physician is concerned the patient may be at increased risk because of family history or their metabolic profile, then CRP may help him decide to give or not to give treatment. And we are well aware that the medical biochemistry laboratories are already stretched thin and there’s no additional budget to measure CRP.

PE What was your reaction to some of the criticism of the JUPITER trial and the suggestions that prescribing statins more widely might not be beneficial?

JG The results are extremely positive, and I think people are leery, just like in the financial world, that if things seem too good to be true maybe it is too good to be true. That’s why if we only had one study of statins we would be skeptical. But we now have 28. Yes, a single study — although well carried-out and well led — needs to be validated. Now, what do we do? Do we wait another five to seven years to do another study, and in the meantime say we’re not sure? Or do we use our best judgement and say, in light of what we know, this is what we recommend? Quite frankly, I’d prefer not to be the smartest guy in the cemetery.

PE Should Canada permit the sale of statins over the counter?

JG No. If you lower LDL a little bit you get a little bit of benefit. The starting dose of an over-the-counter would probably let you lower your LDL by 0.5 millimoles per litre, which would be a reduction of probably 15% in risk. I think that is not significant enough. The message we’re trying to convey with these guidelines is if you decide to put a patient on statins, then do it with a robust dose of a strong statin. I am very strongly against over-the-counter medication for chronic diseases. I think that’s bad medicine. Without monitoring you could develop rare but important side effects and you’ll never know the benefit you derive from these drugs.

Dr Gordon Guyatt

PE What do you think of the emphasis the new application puts on measuring CRP? Doctors don’t test their normal-LDL patients’ CRP levels as a matter of course.

GG I don’t think they should now, either. The issue for any physician informing a patient about their options is to classify the patient as to their cardiovascular risk. Probably the most widely used tool and probably the most reasonable tool to use for that risk stratification is the Framingham risk score. There are others that incorporate CRP but whether there is much to be gained from the application of those scores is uncertain.

PE Would you be in favour of OTC statins, like in the U.K.?

GG Well, look at aspirin for primary prevention of cardiovascular disease vs statins. The effect of statins is almost certainly no less than the effect of aspirin — possibly more — and in terms of its adverse effects is almost certainly no worse than aspirin and probably better. If indeed it is appropriate to have aspirin over-the-counter for the primary prevention of cardiovascular disease, then logic suggests statins would be equally appropriate.

PE Do you think that’s where Canada is headed?

GG I don’t know the psychology of the regulatory agencies or what pressures they’re under, but it would certainly be a not unreasonable way to proceed.