Archive for: June, 2011

Death knell for simvastatin

Jun 10 2011 Published by under Medicine

Simvastatin is a great drug, one I happen to take.  But new restrictions on its use are going to pluck it right off of doctors' prescription pads.  It's not the recommendation against using the highest dose (80 mg) that's going to deliver the death blow; it's the restrictions on its use with other common drugs.

The FDA's new warnings on simvastatin restrict its use with many other common drugs, including a couple of commonly used antibiotics such as erythromycin.  That's not too difficult---people only take antibiotics for short periods of time.  But its use is also limited with some popular heart medications, and since simvastatin is often used in patients with heart disease, this will be a problem.  For example, amlodipine, a popular blood pressure medication marketed as Norvasc, can raise levels of simvastatin.  New recommendations cap simvastatin at 20 mg for patients on amlodipine.

None of these individual recommendations are that difficult to follow, but given our wide range of choices for statins, physicians will have fewer reasons to deal with the hassle.  Why prescribe 40 mg of simvastatin when 40 mg of pravastatin may do just as well (and doesn't carry similar warnings)?  If you suspect your patient is going to eventually need a high dose, why not just bite the bullet and prescribe a branded statin such as atorvastatin (Lipitor) or rosuvastatin (Crestor)?  They are both more potent, and atorvastatin will soon lose its patent.

I can easily see physicians restricting simvastatin to patients with mildly elevated cholesterol and those without too many other medical problems requiring drugs that may interact unfavorably.

Simva, I still like you, but your market share is about to tank.

9 responses so far

Is simvastatin the next Baycol?

Jun 09 2011 Published by under Medicine

As the connection between elevated cholesterol and heart disease became clear, researchers looked for ways to lower cholesterol levels in humans.  A set of compounds known as HMG-CoA reductase inhibitors ("statins") were found to lower cholesterol quite effectively, although some early drugs (i.e. cerivastatin/Baycol) were found to have some disturbing side effects.  Especially when combined with other cholesterol medicines, cerivastatin had a high incidence of  serious muscle damage, much higher than other statins (along with allegations that unfavorable safety data may have been buried by Bayer).  Other cholesterol medications can also cause muscle damage but none to the extent of cerivastatin.  Still, in prescribing statins, physicians monitor patients for signs and symptoms of muscle damage.

Physicians were initially reluctant to prescribe statins, and drug companies such as Merck were quite anxious to sell them.  A lingering problem was lack of data showing that statins could prevent heart attacks and death.  The data showed that higher cholesterol levels put people at higher risk, but before 1994 there weren't good data showing a direct benefit of statins.

In 1994 The Lancet published the Scandinavian Simvastatin Survival Study (usually called "4S").  It was sponsored by Merck, the maker of simvastatin (Zocor), and is considered one of the best and most important statin studies.  Four thousand four hundred forty four patients with heart disease, high cholesterol, and being treated with a cholesterol-lowering diet were randomized to receive either simvastatin or placebo.  The results were dramatic.  They showed significantly reduced deaths in the simvastatin group, and decreased need for invasive heart procedures.  There were few safety problems.

Later studies confirmed many of the findings of 4S, and statins have become an important tool in preventing heart attacks in people with heart disease.   Other benefits have been found as well, and statins seem to have beneficial vascular effects beyond simply lowering cholesterol, but measured levels of cholesterol are still the most commonly used marker to judge the effectiveness of statins.

With all statins, a higher dose produces lower cholesterol levels, an effect that tends to taper off at higher levels (for example increasing simvastatin from 40 mg to 80 mg gives an additional drop in LDL cholesterol of about 6%).  The risk of unwanted effects such as muscle damage may also increase with higher doses, so doctors try to balance the need for lowering cholesterol with the risk of side effects.   Some of the newer statins such as rosuvastatin (Crestor) have increased potency at lower doses and appear to have a lower incidence of side effects at effective doses, but rosuvastatin is a very expensive medication.  Most other statins are available as generics for about 4-10 USD monthly.  Insurance companies have made a very strong push to encourage the use of generics, so doctors and patients are often forced to decide between paying more money, or pushing up the dose---and perhaps the side effects---of older drugs.

Today the FDA announced restrictions (consumer version) on the use of very high dose simvastatin (80 mg). Especially in combination with certain medications and in some patients, the high dose can lead to a higher risk of muscle damage.  They specifically recommended that this dose should be avoided, unless a patient has been taking it for at least a year without problems (the risk is highest during the first year of treatment).  If cholesterol cannot be controlled at lower doses, they recommend changing drugs.

This is going to cause (has already, actually) an avalanche of calls to doctors' offices.  This risk to any individual isn't terribly high, and most patients shouldn't abruptly stop their medications, but people taking 80 mg of simvastatin should ask their doctor whether it is best to keep going or to make a change.

The take home message is that statins are inexpensive, safe, and effective for the prevention of heart attacks and other serious illnesses in many groups of patients, and that it often takes years to sort out the safest approach to therapy.  If you are on a lower dose of simvastatin you should not increase it to 80 mg.  If you have taken 80 mg of simvastatin safely for over a year to control your cholesterol effectively, there is no need to abruptly stop it.  For any patient concerned about their therapy, there are many safe and effective alternatives.

(Full disclosure: I've been taking simvastatin safely for years and have no plans to change any time soon.)

6 responses so far

Old time rock and roll

Jun 08 2011 Published by under Fatherhood, Medicine

"Daddy, is that an electric guitar?"

"Yes dear, it is."

"It's cool! Is it rock and roll?"


"Daddy," she said quietly, almost conspiratorially, "don't tell anyone but I like Bob Seger more than Taylor Swift."

We drove toward her swim class, and Radio Disney was thankfully unavailable.  I put my MP3 player on shuffle, and for once, PalKid didn't freak out.  Van Morrison, The Beatles, Carole King, Elvis Costello, Daniel Lanois, Los Lobos, Miles Davis---all sorts of music poured into the car.  She didn't like it all, but she asked all the right questions.

"Is this jazz?  It sounds like jazz."

"Well, jazz and rock and roll, they're sort of cousins."

"I like the girl singers. Who's this one?"

"Her name is Norah Jones."

"She sings so pretty, Daddy."


We finally made it to the pool.  She was, as has been her habit lately, very clingy. A broad-shouldered swim instructor with a whistle hanging from her lips like a cigarette peeled her off of me and tossed her to the young men in the water.  As I walked away, she began to swim a damned good front crawl, breathing and all.  I haven't taken her to swimming in a long time.  The crowd of mostly young parents was dressed in everything from t-shirts to shalwar kameez and all the kids were cute, but not as cute as my kiddo.  I promised her if she comported herself well (no whining!) we would go to our favorite frozen custard place.

Thank god she did.  There's nothing like real frozen custard on a 95 degree evening, letting my daughter sit in the front seat (in park) and spin the tunes.

At home, it was time to make the beds, set up the IV, tuck in the kiddo, and that's really about all I remember until MrsPal woke me from PalKid's bed to flush the IV.


And medicine keeps happening.  I'm finding that in general, my patients tend to listen to me more than to quacks.  Daily, they offer me clippings or printouts of the latest miracle cures, asking if it's too good to be true.  Thanks to the research I do for my writing, and to the writing of others such as the crew at Science-Based Medicine (from which I've been sadly absent of late), I can tell them not only that it's bunk, but exactly what kind of bunk and why.  The preliminaries dealt with, we can move on to the real business of preventing and treating disease, a job that gets more fun by the day.


5 responses so far

Another day...

Jun 02 2011 Published by under Medical Musings, Medicine

My poor, poor blog.  So neglected.  So much quackery left un-busted.  It turns out that real life can sometimes be more consuming than other interests.  After a significantly disruptive illness, life rarely snaps back to it's previous shape, but slowly takes on new forms and habits.  I no longer have to bathe MrsPal and pack her wounds daily, but I still have to give her IV fluids and help her with medications.  I no longer have to cancel patient time to pick up PalKid or get to the hospital to visit my wife, but she's still a needly little thing (the Kid, that is), clinging to me like one of those stuffed monkeys with the Velcro hands and feet.

And of course, the needs of my patients don't change at all.  An abnormal chest x-ray is just as important no matter what else is happening in my life.  Patients have a doctor, not a team, at least not usually, and that doctor is responsible for gathering and communicating data, facilitating testing and consultations, and all sorts of other time-sensitive work.  Many jobs are like that I suppose, but from my biased viewpoint, doctoring is different.

I'm currently  having an ethical discussion with myself (not aloud) about whether I can make up a bottle of Placebo for PalKid.  At night as attention starts to focus away from her, her throat hurts, or her lip, or some other boo-boo and she wants medicine.  It seems foolish to pump her full of ibuprofen, but she sees me giving Mommy medicine and helping her feel better.  I'll probably never make up that bottle, probably never give her as much attention as she wants, but she'll probably get as much as she needs.

20 responses so far

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