Statins Updated

A poster posited a link between Parkinson's Disease (PD) and Statin use, which led me to an article in Movement Disorders, 2006 (PubMed ID 17177184) that points out, in a retrospective study, a strong link between low LDL and Parkinson's incidence. The lower the LDL, the more people had PD: up to 3 times as often with an LDL below 93.

However, that same article seemed to find a 'neuroprotective' effect for statins. The poster obviously knew more biochemistry than me, so I'm not incredulous, that's just what I found in an admittedly quick search. Updated articles are welcome. It certainly did confirm a link between low LDL and Parkinson's, from which I can infer that LDL is perhaps not entirely deserving of the pejorative 'bad' cholesterol label.

A Google search on statins, however, on the broader issue of Number Needed to Treat analysis, showed very high NNTs, like 33 here, based on a 2003 Lancet article. I'm not sure how reliable that is. However, with an NNT of 33 in people with diabetes, I suppose there is good reason to question statin use given the lack of mortality benefit, and given the serious side-effects; I'm not sure about PD, but pancreatitis and rhabdomyolysis are no picnic.

Just don't ask what the NNT is for epinephrine in out-of-hospital resuscitation. The evidence for a lot of our critical situation algorithms seems a bit thin from podcasts I listen to. Just a tad bit hard to study.

The Cholesterol Controversy, or Are We Getting Fleeced by Statins?

5 billion a year, according to this wellness site that I found with a Google search, is how much the big drug companies are fleecing the public for. A lot of this flap came from the 'failed' Vytorin study, which is unpublished but findable in the Medical Letter here, and in a statement from the American College of Cardiology here.

The study was a randomized trial of people with Familial Hypercholesterolemia and showed no difference--actually, Vytorin was less effective than simvastatin--in slowing the growth of plaque. Forbes said their stock tanked. The wellness site above points to it as evidence that lowering cholesterol is a farce (and, of course, we should buy his book).

The Health Beat blog, which I like but which appears to have a bias against pharma, takes on the topic here. For a bit, I felt betrayed. Here I had been talking to people about lowering their LDL and treating cholesterol for weeks, and the dogma is that statins as a class are being used more and more, not less.

We've been looking at pictures like those at right for years of medical school, learning how to treat it with drugs. Don't they work? Well, actually, yes. Let's talk about endpoints. There is a big study in the Lancet in 2008 (PubMed ID 18191683 at pubmed.gov) that was a meta-analysis of 18,686 diabetics which supported a reduction of 1/3 in major vascular events.

A 2006 study in the Archives of Internal Medicine (PubMed ID 17130382) showed a reduction in major vascular events with NO reduction in all-cause mortality. There was, of note, a 14% reduction in the incidence of stroke.

Critics, including Health Beat, argue that lowering LDL numbers do not affect all-cause mortality and therefore are not useful as there is no quantifiable evidence that quality of life goes up, and there are side effects to statins. True. Also, the Lancet article in particular is a meta-analysis of industry-funded studies, which it admits.

Still, large meta-analyses are about as trustworthy as evidence-based medicine gets, and many drug studies are industry funded.

Are statins a fraud? Just money? A plot by Big Pharma to fleece us of billions?

Of course Big Pharma wants to make money, and tons of it. It is the fundamental mission of private companies to make lots of money and they should. No one should have any illusions about that. This perhaps goes towards why we should have a public health care system. But I digress. The question is if people were fleeced, should ask for their money back, were betrayed, and so on. The wellness sites and others point out that lowering cholesterol naturally with diet and exercise is a better way to do it and statins are a rip-off.

Guess what? We tell our patients that. We say, you should lose weight, eat right, and exercise. A lot. Now. And how many do? In six weeks of primary care, I saw TWO people who had done that. They were healthy, happy, had great numbers and a very high quality of life. We encouraged them, held them up as examples. TWO of them.

So should we avoid treating with statins? If I have a person who, for whatever reason (perhaps because they're a tad lazy) can't lose weight, watch their saturated fat intake, or exercise, should I tell them to just go away? Umm...no. Should I avoid giving an elderly, male, smoking, diabetic a drug that might reduce his chances of having a stroke because he SHOULD quit, eat greens, and run a marathon? No. I'll tell him that every visit. But guess what? He just might not listen.

We should accurately represent what statins do: they make a noticeable difference in the risk of a cardiovascular event, but it is mild. It's not a miracle cure. You should stop if you get muscle aches and so on.

But call them a con and a fleece? Western medicine has said all along that patients should eat right, exercise a lot, not smoke, lower their stress level, and so on. It's easy to jump on the statin 'push' and say doctors and the medical establishment are just in it for the cash, because it absolves all those sedentary junk-food eating patients of any responsibility for their terrible disease burden. As an added side bonus, it often helps sell diet books and alternative medicine, which as far as I know, doesn't come with a money-back guarantee, either. Far from it.

OF COURSE Big Pharma wants to make money. Most doctors (I admit, not all) want to help patients. And we figure that even those people who choose not to modify their lifestyle deserve some recourse to try and prevent badness. Crazy us.

To close the circle, let's go back to the Vytorin study. The drug failed to beat simvastatin with regards to thickness of plaque in people with FH, a rare genetic disorder. So, the endpoint doesn't matter (mortality, heart attacks, and strokes matter) and the population is not applicable to every patient. Is it disappointing? Sure. Does it mean statins don't do anything? No. Patients and doctors shouldn't rely on them to get them out of the work of modifying behavior.

There is no quick fix.

No Hay Disculpas Por El Uso Excesivo!

"There aren't excuses for excessive use". So says the poster about antibiotic use. Shouldn't that be directed at physicians? Aren't we the ones who hold the power to give, or not, that overestimated, well-named Z-pak for sinusitis?

Just the other day a father came in with what sounded like a nasty sinus infection, daughter in tow, 6-month pregnant wife at home, and asked for something to 'wipe out' the nastiness in his head so he could take care of his family. Noble. Hard to refuse. It's not for his gain. The enemy is easy to visualize--the enemy is snot.

It's not, because the enemy is resistance, the best argument yet against the creationists that evolution, despite their protests about intelligent design, is real and happens constantly.

Is there evidence to support giving antibiotics? The studies are numerous. A British Medical Journal article in 2003 found no difference between placebo and Augmentin (amoxicillin plus an augmenting agent) in clinical cure rate, and the patients were selected with 'pus on rhinoscopy' which is how we often do it in the office, rather than x-ray or aspiration (needles into your sinuses). The Cochrane database, a respected organization that collates results, found at best moderate improvement and recommended amoxicillin. The British Medical Journal also has a 'Clinical Evidence' site that summarizes articles they found through 2004 that show no significant difference between treated and untreated patients given placebos in symptoms. So even if we think it will make our patients feel better, it won't, and according to the website, no surprise, there is a significant increase in diarrhea.

Of course, there are other reasons to avoid treating patients. MRSA, on the left, is increasing. A recent Emergency Medicine symposium sponsored by the University of Kentucky (as well as Ortho-McNeil) on CA-MRSA has some interesting points. Penicillin (a relative of amoxicillin, what we typically use for sinus infections) was first introduced in 1941. Resistant S. aureus, the SA in MRSA, was first reported in 1942. Isolated reports of community-acquired MRSA started in the 1980s. A Detroit outbreak in the 1980s showed an increase of resistance from 3% to 38% in only 19 months. In LA, one ED saw MRSA rates increase from 29% to 64% in 3 years. Across the country, an average of 59% of all soft tissue infections presenting to the ED are MRSA.

So what, you might say. What does this have to do with me wanting my Z-pak so I feel better the day after I get sick? Well, how are these increases occurring? We know MRSA is spread by contact, so maybe all these people are really close. Or...surveillance testing of MRSA is conducted by swabbing someone's nostril, where the MRSA lives when it's not invading the lungs or skin or CSF. As seen by the 1941-1942 time gap, penicillin and related antibiotics induce resistance. And we see a quick increase in communities. MRSA lives in the nose, and sinusitis is in the nose, too! So we know we're putting antibiotic pressure on a patient's upper airway.

How much is antibiotic pressure contributing to the rise of MRSA strains? If we give that person with acute sinusitis amoxicillin, are we contributing to the rise of MRSA? I haven't seen a study that documents one way or the other in specific patients with sinusitis, but overall misuse of antibiotics leads to resistance. This article breaks down the major primary care complaints--ear infections, sore throats, and sinus infections--as they relate to resistance.

It gets worse. The same article estimates that up to 10% of CA-MRSA infections are invasive. Osteomyelitis (bone infections, nasty) and pneumonia are being seen in previously healthy patients, and they seem, for whatever reason, to be in young patients. Mortality for CA-MRSA pneumonia ranges from 25-60%, according to the symposium mentioned above.

So there are good reasons not to treat. In the nice clean office with a person snuffling miserably imploring you for antibiotics, who has been told by all their friends that all they need is a Z-pak to 'nip that thing in the bud', it's hard to hold the line. I heard a story the other night of one parent telling another to go get a burst of prednisone, really strong medicine with significant side effects, for their kid's cough. Not trouble breathing or major asthma exacerbation, their cough. But what's our job? To make people comfortable? Sometimes. But we can do that with supportive care and empathy. Our other job is to try and prevent them from dying or being sick for the rest of their lives. For that part of our job, we should send them home most, if not all of the time, or at least until they've had 7 or more days of serious symptoms.

I Wish It Were Cat Scratch Fever

A tale of black cats and clear vodka in multiple acts. The chief complaint is a cat bite. I go in to talk to the patient, and sure enough, she has a tiny cat bite on her shin that looks to be healing well, but is exquisitely tender along the tibia and up around the knee.

Cat bites are a favorite of medical students because they can cause Cat Scratch Fever due to Bartonella henselae; one of the cooler diseases by name and because there's a Ted Nugent song named after it. Short of that disease, cat bites are notorious for causing infection because, as one attending put it, 'their teeth are like hypodermic needles for injecting bacteria'. One more reason cats are cute...from afar. I'll stick with Golden Retrievers, thanks.

The patient is dressed in jeans, hiking boots, an old sweater. She has a calligraphic tattoo on her neck. Any other symptoms? Speech is slurred. Well, diarrhea, she says. Green, the color of the paint on the wall (no, we don't have poop colored walls. Kelly green). And I throw up like clockwork every day at 5 or 6 am, and again at 7 am, so I can't take my medicines.

Were you sick before you had the cat bite? Well, yes. Part of me is disapointed, in a fit of moral obfuscation I'll talk about in a later post. No Cat Scratch Fever. But she has had fevers, and chills. And abdominal pain. And shortness of breath. Her exam reveals lungs that sound like a hyperactive gnome playing with tin foil. Her abdominal exam shows marked guarding (muscles tense with any pushing) under the ribs on the right and just below the bottom edge of her sternum.

Sometimes I go into a room without reading the chart a lot in order to simulate my future life with its total lack of any sort of continuity with the exception of drug seekers and cold homeless people.

So, I was thinking, gosh, could this be pancreatitis? Ulcer? Sepsis secondary to the cat bite was unlikely, no matter how much I wanted the cat bite to be something interesting.

To be safe, I read the chart. She had presented with exactly the same thing, minus the cat bite, three weeks ago, and again before that, so on and so on for years. Further questioning revealed that she had also been drinking a liter of Vodka, again. She has had elevated lipase levels and acute pancreatic attacks before. Probably was pancreatitis again. But it wasn't from the cat. The poor cat bit her because she was ataxic from the vodka and about to step on her kittens. And, oh yeah, the meds she couldn't take were psych meds.

My first car was a 1974 Volvo station wagon that couldn't get over 50 MPH even on a downhill, but somehow managed to keep running for years. Every once and a while I would change a hose, change the oil, get in a fender bender, have a friend jump on the roof at a party and dent it irreparably. The steering wheel lost it's cover one day. It just fell off. But eventually we sold it, still running. I saw it one day downtown, still going.

Some patients are like that. I can't for the life of me figure out how they keep going, but they do, with their panaloply of ailments, dragging through life. I haven't solved them yet. I wonder if I will. Until then, it'll be easy to form compassion for them. I used to love that old car too, even when it didn't work so well.

You're Fine, Go Home

Ah, clinic.

Not the ED. Being in clinic makes me respect the family practitioner. Most of the time they are given 15 to 20 minutes total, even at an academic clinic, and 10 of that gets eaten up by the nurse rooming the patient. Once they enter, they have to (and often want to) receive an update on the rest of the family.

And then they have to proceed with the sorting. Sort the lipids, sort the glucose readings, sort the thyroid hormone levels, and sort the day-in day-out wheat from the dying chaff.

Because it's very possible to miss someone sick. In the ED, at least we have the luxury of saying, 'what esoteric disease might kill this patient soon?' and then doing our work-up within the next hour for that. But in the clinic, any test takes time, most people aren't sick, and the pressure is to move them out. Improve their lipids, improve their BP.
But don't miss. To actually tell someone, 'go home, you're fine' after you've considered with a fair amount of energy all the terrible things that can happen to them is more difficult. You find yourself wondering what's in their CSF--is it meningitis (Neisseria meningitidis, as above)? Can you rule it out on history alone?

The studies say yes, sometimes. The studies say you can irrigate lacerations with tap water. But it's different to be confident enough to do it. One girl recently, 11, good in school, came in to make sure she didn't have meningitis as her mother had been admitted the other day. My thin-slice thought (immediate impression, read Blink for more) was that she was fine. But I had to check.

Any confusion? No, but really sleepy. She fell asleep in class. Did she leave early? Yes. What did she do at home? She ate and did her homework. Well, that feels better. How about today? Just tired. But she's not confused. Headache? Yes. Worst in your life? No. You've had worse? (I want to be clear). Yes.

On exam, her chin tucks all the way to her chest, smoothly. As her head travels the parabola dictated by her spine in front of me I exhale without knowing I was holding my breath. JAMA, 1999--in the absence of fever, neck stiffness, and altered mental status, an adult is 99% certain or more to not have bacterial meningitis. Go home, you're fine.

On the next afternoon, a fifty year old with a heart attack last year comes in with a cough for a month. Then he mentions palpitations. Then he says when he climbs stairs he gets pain radiating into his left chest that reminds him of his heart attack. Then he says he's sleeping on 5 or 6 pillows at night. Go home? You're fine? Er, no.

Normal ECG, normal chest x-ray doesn't help rule anything out except we're not calling an ambulance. But it's the clinic. So long story short, go home, you're maybe fine...just follow up with cardiology for a stress test. And make sure to come back if things get worse. And please, please, please, follow up. Then he left. That was stressful. That judgement is trickier than trauma.

And my respect for the family practitioner went up. I didn't have the luxury of a chest pain unit, or serial enzymes, or serial ECGs. It was 4:30 on a Friday. I had nothing. I was lucky to get the chest x-ray. Sort the lipids, sort the glucose levels, sort the blood pressures...and don't miss the MI. By the way.

Stressful, when you start to realize that people's lives are, if even for a matter of minutes, in your hands. It's not like 3rd year with residency on the horizon.

Chief Complaint

"I am suicidal and I would like to review my cholesterol."

We use the chief complaint to describe what a patient is coming in for; it should be in the patient's own words. The above was an actual CC in a chart for a family practice visit.

You have 15 minutes to work with the patient. Go!

I think family practice docs don't ever get enough credit. They have to deal with such a wide scope of problems that it's unbelievable. Perhaps even more amazing about the visit above is that the doc addressed both concerns. His assessment at the end of the note went something like, 'we agreed that she was not in imminent danger of harming herself; the patient was given hotline numbers if the situation worsened. Her most recent triglyceride value was 488; we discussed staying away from fatty and fried foods in addition to her normal medication regimen.'