In case you haven't heard, this is the trial that showed that healthy middle-aged people (men over 50 and women over 60) with normal cholesterol levels (LDL less than 130) but high levels of C-reactive protein (CRP) had fewer deaths, especially cardiovascular deaths, when they took 20 mg of the statin Crestor.
Reactions have ranged from the gushing of some reporters who suggest that we should put statins in the drinking water to the lambasting by writers who say the trial was just another gimmick by wicked pharmaceutical companies trying to sell expensive drugs (Crestor costs more than $3 a day) that will hurt or even kill us.
My position is intermediate between these extremes. Drugs can save lives. Drugs can also kill. In some cases, a drug that saves the live of one person might fail to help, harm, or even kill another person. How do we know which one will benefit us?
In 50 or 100 years, if civilization survives that long, we'll probably have genetic/metabolic profiling tests that will allow physicians to determine which drug will benefit which particular patient. But that time isn't here yet, and we have to make some guesses. Physicians often prescribe one drug and have the patient check back to see if it's working without side effects. If not, the physician tries another drug. But it's pretty hit or miss.
Studies have shown that statins help younger men who have already had heart attacks. Evidence that they help older women has been lacking. One good thing about the JUPITER trial is that it did include women, and the women seemed to benefit more than the men.
Remember that a lack of evidence doesn't mean that something isn't true. It just means it hasn't been proved yet.
I don't think there's ever been a randomized, controlled, double-blind study that proves that aspirin helps headaches. But most of us agree that it does. Or maybe it's all just a placebo effect. I have a friend who claims that only cheap aspirin helps her headaches; the expensive brand names don't work, she says. I once had an experience in which plain aspirin knocked out the pain from a bad earache but aspirin plus codeine had no effect because I thought those pills were antibiotics.
One problem we face when trying to decide whether or not to take any drug is that there may have been studies showing that the drug was effective -- or dangerous -- in a particular population, in this case healthy, nondiabetic middle-aged men and women with normal cholesterol levels and elevated CRP levels, but there may be no proof that it will work for people like us.
In the JUPITER trial, for instance, people with diabetes were excluded. And recent studies have suggested that low-dose aspirin therapy, which has been shown to reduce cardiovascular events in the general population, are not effective in people with diabetes.
But then, are "people with diabetes" people who have been diagnosed with diabetes regardless of their control? Or are they people with high BG levels as expressed in A1c levels of 9 or 10 or even higher? What if we have diabetes but we maintain A1c levels below 6, or even below 5? Should we then consider ourselves with the general population (aspirin will help us) or with the people with diabetes (aspirin won't help us)?
There have never, to my knowledge, been studies of populations of people with diabetes who maintain their hemoglobin A1c levels between 5 and 6. Those studies will probably never be done because the benefits of drugs in those populations are not apt to be as great as those in populations with higher A1cs, and in order to get FDA approval, the drug companies want to show the greatest effect possible.
There are many other reasons to point out that this one Jupiter study doesn't prove that statins will help almost everyone. The study was stopped after a median of 1.9 years because the benefit of the statin seemed so clear. Hence we have no idea of the long-term effects of such statin use.
As many have pointed out, fatal heart attacks were actually greater in the statin group. But fatal strokes were greater in the placebo group, so they balanced out: 12 deaths of both kinds in both groups.
Diabetes rates were also greater in the statin group, and A1c was slightly higher (a median of 5.9 vs a median of 5.8 in the placebo group). No one understands why. But there were more deaths in the placebo group (247 vs 198 in the statin group) and more cardiac-related deaths (157 vs 83 in the placebo group).
If cardiac deaths are related to A1c levels (there is evidence for this), then those who died most likely had higher A1c levels than those who survived, so the average A1c level in the placebo group would have been lowered through attrition more than the level in the statin group.
So many unknowns. The more I learn about health, the more I realize how little we know. Making decisions about which drugs are best for us is not simple. When we have diabetes, we're considered to be in the same risk category as someone without diabetes who has already had a heart attack. But being in the same risk category doesn't mean we're in the same therapeutic category.
A study showing that people who have already had a heart attack will benefit from a drug doesn't necessarily meant that people with diabetes who haven't had a heart attack will benefit from the same drug, even though they're considered to have the same risk.
Some people say that although statin drugs reduce cholesterol levels, their therapeutic effect is actually because they're anti-inflammatory. This may well be. But if that is true, why is no one doing comparison studies to see if other anti-inflammatory drugs will work as well as statins in preventing cardiovascular disease?
Low-dose aspirin, an inexpensive anti-inflammatory drug, reduced cardiovascular events in the general population. But it didn't seem to work in people with diabetes. How about higher doses of aspirin, or other anti-inflammatories?
Salsalate, an anti-inflammatory drug that releases aspirin in the intestine, has been shown to reduce A1c levels in people with diabetes, as well as improving other parameters, including CRP levels.
Unfortunately, the high doses of salsalate used in these "proof of principle" studies were also not without side effects typical of aspirin, including ringing in the ears. Lower doses had fewer side effects but were also not as effective in reducing A1c and other parameters of interest to people with diabetes.
Some people who take statins have serious side effects, including muscle pain and memory loss. Does it make sense to take an expensive drug with potentially serious side effects to try to prevent some future event?
I think this depends on your own individual risk profile. If no one in your family has had heart disease and they've all died from cancer at an advanced age, then it would probably not be worth the risks of the drugs. But if everyone in your family has heart disease and many have had heart attacks in their 40s and 50s, the risks would probably be smaller than the benefits.
I take a statin myself, as well as ezetimide (Zetia). In fact, I take them in combined form, as Vytorin, the drug that was shown to decrease cholesterol levels more than a statin alone but not to decrease the level of plaque buildup in the carotid artery any more than the statin alone. Some have also suggested that the drug may increase cancer rates. After the results were announced, many medical people recommended using a statin alone in people with high cholesterol.
A nice idea in theory, but statins alone didn't reduce my cholesterol levels one iota; they remained around 300 to 400. If my cholesterol level were 210 or 220, I'd probably think it wasn't worth the risks of the combination drug. But with the combination of diabetes, cholesterol levels that high, a preponderance of the dangerous small-dense LDL, and a family history of heart disease, I think it's prudent to take cholesterol-reducing medication. I've never had muscle aches from taking a statin.
If statins alone work for you, then it wouldn't make sense to add a drug like ezetimide. If you can improve your lipid levels with diet alone, or if you get muscle aches when you take statins, then even the statin would not be a good idea for you. If you know that you have the beneficial light, fluffy cholesterol and not the small-dense kind, then taking a statin would probably not be worth the risks.
It would be nice if decisions about drugs were black and white, if all medical decisions were simple, if we knew that Drug A was the best and worked for everyone, with no side effects. Unfortunately that isn't true, and we all need to learn as much as we can about every drug we take (as well as drug interactions) and then, together with a physician we trust, make a decision on the basis of our own unique physiology.
It's not easy; but it's important.
Published On: November 13, 2008