CW: Three new Statin safety issues

I can’t help myself. The draw is so strong.

It’s simply not possible to stay silent on the recent news about statins.

Yesterday, the FDA announced important changes in the safety language that comes in the package insert of statin drugs. (I’m late to the show here, as twenty-four hours is an eternity in medical news.)

Here are the three bullet points: (with my comments in italics)

1. Increases in blood sugar levels (hyperglycemia) have been reported with statin use. Numerous studies have indicated that patients on statin drugs develop the “diagnosis of diabetes” at a slightly greater rate than those taking placebo.

The increased signal of diabetes in patients taking statin drugs is real. Slight, but real. Experts disagree about the significance of statin-induced blood sugar effects. Some say that the overall benefits of statins far outweigh small changes in lab values. These blood-sugar minimizers point to the potent lowering of heart attacks, strokes and death in patients taking statins. In making this argument, statin protagonists cite secondary prevention studies—those that look at how statins prevent second heart attacks and stroke.

While other experts, the blood-sugar worriers, emphasize the disastrous effects of high blood sugar on blood vessels. This camp talks about the high ‘numbers-needed-to treat” (NNT) when statins are used in low-risk patients, like cyclists, children and adults without risk factors for heart disease. Minimalist doctors worry that the long-term risks of statin-induced diabetes may outweigh their heart-protective effect.

My take home:  The greatest risk to a patient who suffers a heart attack or stroke is another heart attack or stroke. Statin drugs break this spiral. I am convinced that the single most important pill that a heart attack patient swallows is a statin, regardless of their cholesterol level. That said however, I am far less certain, pessimistic even, that statin drugs prevent trouble in low-risk patients. This is because—over the long-term–small benefits can be neutralized by small harms.

2. Sudden memory lapses: Certain cognitive (brain-related) effects have been reported with statin use. Statin labels will now include information about some patients experiencing memory loss and confusion. These reports generally have not been serious and the patients’ symptoms were reversed by stopping the statin.

The many-in-number and internet-fueled statin naysayers run with this emotionally charged concern. These rabble-rousers post that statins cause brain damage and psychiatric disorders. Levelheaded Forbes journalist Matt Herper dumps cold water on these inflamers. How? He uses a potent elixir: the real data. This quote, cited in Mr Herper’s Forbes piece, comes from this FDA briefing document.

“18 [of 8900] rosuvastatin-treated subjects versus 4 placebo-treated subjects [from the Jupiter trial] experienced the AE [adverse effect] of “confusional state”. Six of the 18 confusional states in rosuvastatin-treated subjects were considered as a SAE [serious adverse effect]. Two subjects were not on study medication at the time and others had concurrent medical conditions and/or medications ongoing at the time of the event.”

Believe it or not, I actually looked at the 100+ page FDA document. (Yes, it’s painful for big-picture people to look at this much minutia.) The striking thing was that of these 16 patients with presumed statin-induced confusion, most were older and had other medical problems often associated with thinking trouble. So it’s hard to get excited about confusion in 16 of 9000 patients. If we held other drugs to this high standard, there would be few pills—or at least few with biologic actions—available to patients.

Here’s another thought on statins and brainpower: It’s clear that these drugs smooth arteries and prevent strokes. One of the leading causes of dementia is poor blood flow to the brain—medical people call this multi-infarct dementia. It’s equally attractive, optimistic even, to surmise that statin-induced healthier arteries may preserve brain function.

3. Routine periodic monitoring of liver enzymes is no longer required: Serious liver injury associated with statins is “rare and unpredictable in individual patients” and “routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing this rare side effect,” according to the FDA. The FDA now says that liver enzyme tests only need to be performed before starting statin therapy and “as clinically indicated thereafter.”

This refreshing injection of common sense inspires hope. Whenever common sense recommendations make it through the morass of regulation, I cheer. Why measure something if knowing it doesn’t influence outcomes? For the record, few cardiologists regularly monitored liver enzyme abnormalities in patients on statins.

Conclusion:

I love thinking about statins. They are so in the sweet spot of what interests me about practicing Medicine. Here are potent chemicals with complex and yet to be discovered actions that have potential downsides but often huge upsides for some.

That these pills compete with, or synergize the effect of my favorite therapy—making good food choices, exercising, sleeping and smiling—only enhances their blogging potential.

JMM