Crestor Prevents Heart Attacks and Strokes in Patients with Normal Cholesterol and High CRP

“If you think health care is expensive now, wait until you see what it costs when it’s free.”
— P.J. O’Rourke

I’ve written several times about the proven benefits of a family of cholesterol-lowering medicines called statins.  Statins include the medications Crestor, Zocor, Lipitor, Mevacor, Pravachol and others.  The group has a solid base of evidence showing that they prevent strokes and heart attacks in patients with high cholesterol and in patients who have had a stroke or heart attack.

This week, a study published in the New England Journal of Medicine brought us more good news about statins, and potentially broadened their usefulness.  The study has received a lot of attention in the mainstream press.  The study randomized over 17,000 patients who:

  • were men over 50 or women over 60
  • did not have a history of heart disease, stroke or diabetes
  • had normal cholesterol (LDL < 130)
  • and had an elevated C-reactive protein ( > 2)

C-reactive protein (CRP) is a blood test that is a general marker for inflammation.  CRP has long been known to be elevated in people at higher risk for heart attack, but until now, there’s never been anything known to decrease that risk.

The patients were randomized to Crestor 20 mg daily or placebo and were followed for an average of almost two years.  The patients on Crestor had fewer heart attacks, fewer strokes and fewer deaths from any cause – a pretty remarkable finding in a group of patients who are not at high risk of cardiovascular illness.

These results strongly support checking a CRP in older men and women and considering statin therapy in those with an elevated CRP regardless of their cholesterol levels.  There are some caveats, though.  This group of patients had a fairly low risk of adverse events and it took a very large number of patients to show a difference between Crestor and placebo.  Extrapolating from the results of the study, it would take treating about 277 patients for two years with Crestor to prevent one heart attack, and 346 patients to prevent one stroke.  Using the current price of Crestor, the cost of Crestor needed to prevent one adverse event is over $170,000.  The price would be less with a generic statin, but it’s still a big expense and a lot of patients taking a statin who don’t benefit.  But we don’t know ahead of time who is the one patient who will have the stroke or heart attack.

So will I recommend checking a CRP to my older patients?  Yes.  Will I recommend statins to patients with an elevated CRP?  Probably, but with the explanation that the benefit may be quite small.

Economists call this the law of diminishing returns.  The more resources you spend on a problem (in this case, stroke and heart attack prevention) the less benefit you get from each incremental increase in spending.  At some point the possible benefit is so vanishingly small that costs aren’t worth it, but that point is different for every patient.  Each one of us has different preferences, different attitudes about risk, and different ways to spend our finite resources.  In a free market each patient would balance the risks and benefits herself, but in our current system in which we all indirectly pay for each other’s medicines the decisions will likely be made by insurance companies and by national expert groups.

(I’m grateful to my colleague Dr. Roy Artal and to the several patients who emailed me about this story.)

Learn more:

New England Journal of Medicine article: Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein

New York Times article: Cholesterol-Fighting Drugs Show Wider Benefit

USA Today article: Crestor would save lives at $500,000 each

More

In Women after Menopause, Testosterone Patch Improves Sexual Interest

“I can’t get no satisfaction”
— The Rolling Stones

Many women after menopause experience decreased interest in sex and decreased satisfaction with sex.  Some women accept this as a natural part of the aging process, but other women are quite distressed by these symptoms.  The Diagnostic and Statistical Manual of Mental Disorders, the authoritative text on defining psychological illness, even lists “hypoactive sexual desire disorder” as a disorder marked by a lack of sexual interest which causes personal distress or interpersonal difficulties.

This week’s issue of the New England Journal of Medicine published a study attempting to treat these symptoms.  Not surprisingly, the study was widely covered in the general press.  In the study, post-menopausal women who reported a decreased interest in sex and significant distress related to this were randomized to either a patch that released a small amount of testosterone or placebo.

Twenty-four weeks later, women using the testosterone patch reported significantly greater interest in sex and more frequent satisfying sexual episodes than women using the placebo patch.  Women using the testosterone patch also reported significantly less distress about their sexual health than women using the placebo patch.

The women were followed for a year to monitor side effects.  The most common side effect was unwanted facial hair, reported by 20% of women on the testosterone patch and 10% of women on placebo.  (There was no note of how this side effect impacted their partners’ interest in sex.)  There was also some skin irritation at the site of the patch.

This study was too short to find any long-term risks of testosterone.  As with any hormone, the most serious concern is that it may increase the risk of breast cancer.  So while this study may offer a possible helpful advance for post-menopausal women, safety concerns will have to be answered before women can use it with confidence.

Learn more:

New England Journal of Medicine article: Testosterone for Low Libido in Postmenopausal Women Not Taking Estrogen

Wall Street Journal article: Patch Boosts Libido for Some Older Women

Los Angeles Times article: Testosterone makes women friskier — but should it be prescribed?

More

The Aspirin Controversy, Part II

My post last week created much confusion and worry.  I received many emails asking “What about me?  Should I keep taking aspirin or not?”

Let me clarify the issue by explaining what we already knew before last week’s study in the British Medical Journal.  We knew that aspirin is valuable in:

  • patients who have had a stroke
  • patients who have had a heart attack
  • patients who have had bypass surgery or angioplasty
  • patients with angina (chest pain or discomfort caused by narrowing of coronary arteries)
  • patients with claudication (calf pain caused by narrowing of leg arteries)

So patients in the above groups should take aspirin unless they have had an adverse reaction from aspirin.  Last week’s study was not about those patients.

Last week’s study was about patients with multiple risk factors for heart attack but who had not had a heart attack or a stroke.  Risk factors for heart attack and stroke are:

  • age (men over 45, women over 55)
  • smoking
  • high blood pressure
  • high cholesterol
  • diabetes
  • a parent or sibling with a heart attack early in life (male relative before age 55, female relative before age 65)

The US Preventive Services Task Force (USPSTF) and the American Heart Association (AHA) currently recommend aspirin to prevent a first heart attack or stroke for patients with multiple risk factors for heart attack and stroke.  Last week’s study disagreed with those recommendations, suggesting that aspirin does not prevent a first heart attack in high-risk patients.

My friend and colleague, Dr. Yaron Elad, emailed me arguing that I should not change my practice based on a single study.  He and I dug through the studies supporting the USPSTF and AHA recommendations and decided that he was right.  There is still a lot of evidence that aspirin helps prevent a first heart attack in patients at high risk of heart attacks.  So I retract my conclusions last week, and I’m grateful for Dr. Elad’s input.

Finally, and most importantly, talk to your doctor before making a decision.

Learn more:

My post from last week: Aspirin Doesn’t Prevent Heart Attacks in Patients with Diabetes

The US Preventive Services Task Force recommendation: Aspirin for the Primary Prevention of Cardiovascular Events

American Heart Association recommendation: Aspirin in Heart Attack and Stroke Prevention

More

Aspirin Doesn’t Prevent Heart Attacks in Patients with Diabetes

Aspirin has been a mainstay in the treatment and prevention of cardiovascular disease for decades.

We know that in patients who have had a heart attack in the past aspirin prevents a second heart attack, and during a heart attack aspirin is life-saving.  We also know that in patients with a prior stroke aspirin prevents further strokes.  And in patients with symptomatic narrowing of the arteries, that is chest pressure with exertion (angina) or calf pain with walking (claudication), aspirin prevents strokes and heart attacks.

So on that solid base of evidence, doctors have extended aspirin therapy to many other patients who don’t fit the above criteria but have risk factors for heart attack and stroke, risk factors such as diabetes, smoking, high blood pressure and high cholesterol.  Practice guidelines have been formed recommending aspirin for such patients, despite the lack of evidence that it helps them.  I’ve urged many patients with diabetes, high blood pressure and high cholesterol to start taking daily aspirin.

Well, there’s nothing like a good study to show us that we’ve been doing the wrong thing.  The British Medical Journal published a study this week in which 1276 patients with diabetes and mild, asymptomatic narrowing of the arteries were randomized to receive daily aspirin or placebo.  They were followed for over 6 years to assess differences in the rates of heart attack, stroke, amputations and death.  The surprising result was that the aspirin group did no better than the placebo group.  Aspirin didn’t help.

(By the way, the study also randomized patients to receive antioxidants or placebo, and the antioxidants didn’t help either.)

So to summarize, aspirin should be taken by patients who have had a previous stroke or heart attack, or have symptoms of artery narrowing, such as angina, claudication, or a prior angioplasty or bypass surgery.  Patients taking aspirin because of risk factors for heart disease who have no symptoms of artery narrowing (even though I urged some of you to start aspirin!) should stop.

(Thanks to my colleague and pal, Dr. Rubencio Quintana, for showing me the British Medical Journal article.)

Learn more:

British Medical Journal article: The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

UPDATE:  In a subsequent post I retracted my conclusions, offered some balance to the controversy and urged readers to talk to their doctors before changing their aspirin regimen.

More

Take a Big Breath

I beg your indulgence this week as I ignore medical news and offer some personal reflections.

Unless you’ve been avoiding all news sources for the last few weeks, you know that a lot of people all over the world are scared.  Today’s headlines scream about the worst week ever on Wall Street, with trillions of dollars of assets evaporating.  No one is sure when the housing and credit markets will stop falling.  No one is sure whether the actions of the U.S. and other governments to keep credit flowing will work.

And this calamity did not befall an otherwise tranquil world.  Those who were paying attention had plenty of other reasons for anxiety, from a nuclear-armed Pakistan that always seems one election away from anarchy to our federal budget becoming an unworkable fantasy as the baby boom retires.

The sky really seems to be falling.

I’m not an economist, and I can’t predict when or how this will end.  I certainly won’t minimize the very real harm that’s been done.  The staggering numbers aren’t just theoretical paper losses.  They represent the vanishing of retirement plans, the loss of homes, and the destruction of years of gains.

All I can do is remind us that the world will not end.  At some price buyers will want houses again.  At some interest rate lenders will write loans again.  If governments keep their currencies stable, markets will eventually hit bottom and stabilize.  The engine for economic growth after all is that people want stuff that they don’t have, and that they are willing to work and spend for it.  That hasn’t changed.  The sun will come up tomorrow.

So to quote Douglas Adams, don’t panic.  Take a walk, preferably with someone you care about.  Listen to some music that has survived over a century.  And take a big breath.

More

Medications for Osteoporosis

The current issue of the Annals of Internal Medicine published a clinical practice guideline from the American College of Physician on drug treatment for low bone density.  It contains a valuable review of the known benefits and risks of the medications used for osteoporosis which I summarize below.

Bisphosphonates

This family of medicines includes Fosamax, Didronel, Boniva and Actonel.  Fosamax, Didronel, Boniva and Actonel have been proven to prevent vertebral fractures, and Fosamax and Actonel have been proven to prevent hip fractures.  Boniva has not been shown to prevent non-vertebral fractures.  The most common side effects of bisphosphonates are gastrointestinal: acid reflux, esophageal irritation, and nausea.  Bisphosphonates have also been linked to destruction of the jaw bone, a very rare but more serious side effect.

Calcitonin

Calcitonin nasal spray has been shown to prevent vertebral fractures though the evidence is less strong than for bisphosphonates.  Calcitonin does not prevent non-vertebral fractures.  It has no serious side effects.

Estrogen

There is strong evidence that estrogen prevents vertebral and non-vertebral (including hip) fractures.  But there’s also good evidence that estrogen increases the risk of blood clots and stroke.  In combination with progestin, estrogen also increases the risk of breast cancer.  Without progestin it increases the risk of uterine cancer.

Forteo

Forteo is a relatively new treatment for osteoporosis.  It is taken as a daily subcutaneous injection, making it less convenient than oral medications.  It has been shown to prevent vertebral fractures, but its effect on non-vertebral fractures isn’t clear.  It has no serious side effects.

Selective Estrogen Receptor Modulators (SERMs)

The two available SERMs are Evista and tamoxifen.  Tamoxifen is not useful for fracture prevention and is not used to treat osteoporosis.  Evista has been shown to prevent vertebral but not non-vertebral fractures.  Evista increases the risk of blood clots.

Calcium and Vitamin D

The evidence on calcium and vitamin D for fracture prevention is mixed, with the most positive studies showing modest benefit.  Calcium and vitamin D have no serious side effects.

Learn more:

Summaries for Patients:  Drug Treatment for Low Bone Density or Osteoporosis to Prevent Fractures

American College of Physicians clinical practice guidelines:  Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures

More

Better to Give than to Receive

For the last couple of years I’ve made a commitment to donate blood every month or two at Cedars-Sinai.  Though I must admit the first few times I was scared by the whole experience, I almost look forward to it now.  The nurses treat the regulars like old friends, and the donors are treated to a mandatory break from their busy lives.  Since we can’t be productive, we listen to music, or watch TV, or pick a movie from their eclectic selection.  (Oddly enough, I’ve found that gory horror movies are my favorite when I’m donating.  Nothing distracts me more effectively from the fact that I’m being bled than a good vampire movie!)

I was donating last week when a nurse told me that their blood supply has been very low.  Several of the Metrolink crash survivors are at Cedars-Sinai and have used a lot of blood products.  That’s when I realized that it’s been two years since I last begged all of you to donate.

So please contact the Cedars-Sinai Blood Donor Facility and schedule an appointment to donate a little bag of liquid life.  If donating at Cedars is inconvenient, go to the Red Cross blood donation website and find a donation center near you.  You’ll be rewarded with juice and cookies and the best feeling you’ve had in a while.

Someone you’ll never meet is counting on it.

More

Get Your Flu Shots

The first day of fall is three days away.  The kids are back in school, temperatures are dipping lower and the leaves on the trees in LA are doing nothing.  In this magical season a doctor’s thoughts turn to flu shots.

The flu shot is recommended for the following groups:

  • Children aged 6 months until their 5th birthday,
  • Pregnant women,
  • People 50 years of age and older,
  • People of any age with certain chronic health conditions (such as asthma, diabetes, or heart disease),
  • People who live in nursing homes and other long-term care facilities,
  • Household contacts of person at high risk for complications from influenza,
  • Household contacts and out of home caregivers of children less than 6 months of age, and
  • Health care workers

The following people should NOT receive the vaccine:

  • People who have a severe allergy to chicken eggs,
  • People who have had a severe reaction to an influenza vaccination,
  • People who have developed Guillain-Barre syndrome within 6 weeks of getting an influenza vaccine,
  • Children less than 6 months of age (influenza vaccine is not approved for this age group), and
  • People who have a moderate to severe illness with a fever (they should wait until they recover to get vaccinated).

For everyone else it’s optional.  If you’re not in one of the above groups and want to avoid the flu, get vaccinated.  Our office has received this year’s flu vaccines.  If you’re a patient who wants one, please call for an appointment.

Learn more:

The Centers for Disease Control and Prevention 2008-09 Influenza Vaccine page

More

Arthroscopic Surgery Ineffective for Knee Arthritis

Arthroscopic surgery is a common treatment for moderate to severe knee arthritis.  Through scopes inserted through small incisions the knee is irrigated and irregularities in the cartilage are shaved off.

In fact, no study has ever demonstrated that this surgery is effective for arthritis.  Even worse, in a study in 2002 that randomized patients with knee arthritis to either arthroscopic surgery or sham surgery (in which skin incisions are made but nothing is done to the joint), the surgery group did no better than the sham surgery group.

Nevertheless, old habits die hard, especially when the habit is a very lucrative but ineffective procedure.

This week a study in the New England Journal of Medicine helped solidify the negative scientific data for arthroscopy for knee arthritis.  In the study patients with moderate to severe knee arthritis were assigned to two groups.  One group received arthroscopic knee surgery, physical therapy and medications.  The second group received only physical therapy and medications.  There was no difference in symptom scores between the two groups during the following 24 months.

Experts are now asking orthopedists to stop offering this procedure for arthritis patients.  Of course, many ethical doctors won’t do ineffective procedures, but others will simply shoot the messenger and criticize minor flaws in this study.  As long as some insurance companies pay the bill, some doctors will continue to offer it.

In a free society we can’t get rid of a bad product by shaming the providers.  We do it by educating the customers.

Learn more:

New York Times article:  A Study Revives a Debate on Arthritis Knee Surgery

New England Journal of Medicine study:  A Randomized Trial of Arthroscopic Surgery for Osteoarthritis of the Knee

More

Gamma Rays are Good for Your Veggies

Last month the Food and Drug Administration allowed food manufacturers to irradiate fresh lettuce and spinach to kill bacteria.  The decision resulted in some controversy and much press coverage.  (See link to LA Times article, below.)  The process involves shooting gamma rays through the produce in an amount enough to kill most bacteria but not enough to wilt the leaves or affect the taste.

Though food safety advocates have been recommending food irradiation for many years as a reliable way to decrease food-borne illness, the procedure has been persistently blocked by public fear and misunderstanding.

Few technologies are as distorted and maligned in the public imagination as radiation.  After all, if all you know about gamma rays is that they transformed scientist Bruce Banner into the Incredible Hulk, why would you possibly want them transforming your spinach?  (Don’t get me started about fears of cloning.)

The important thing to keep in mind is that irradiated food doesn’t give off radiation, just like you don’t become radioactive after a chest X ray.  Radiation goes through your chest, but no source of radiation ever enters your body, so you don’t emit radiation afterwards.  Similarly, irradiated lettuce is not itself a source of radiation.

So it was expected that the FDA’s announcement would lead to an outbreak of luddite hand-wringing.  An analyst for a political advocacy group (quoted in the article below) warned that “irradiation masks the unsanitary conditions of industrial agriculture.”  Well, sure, just as seatbelts mask the dangerous conditions of car accidents.  No one suggests that food irradiation should lead to more lax farming standards, just as seatbelts shouldn’t lull us into reckless driving.  The other criticism, typical of all new safety technologies, is that it’s not perfect.  That’s true.  The number of food-borne illness will decrease, but not to zero.

Safety derives from multiple redundant measures that each decreases our risk.  Food irradiation is a valuable and long-overdue common sense practice.

Learn more:

Los Angeles Times article:  Irradiating iceberg lettuce, spinach effective but not fail-safe; critics cite consequences

More