Do Not Stop Your Statins

As my tween daughter would say, "OMG!"
The media is a buzz with the news that the FDA is changing the warnings on statins.
The New York Times claims "Safety Alerts Cite Cholesterol Drugs’ Side Effects."
According to the Wall Street Journal "FDA Warns on Statin Drugs."
And the text on the bottom of the CNN report states "FDA places warning on statin labels."

Statins, which are cholesterol lowering medications are now one of the most commonly prescribed medications in the US. If I were one of the millions of patients taking a statin, I would be pretty worried based on what I am hearing from the media. 

Fear Not!  There is Nothing to Worry About.  Do Not Stop Your Statins!

Before getting in the details, it is important to note:

1. It is pretty irresponsible of the media to use scary headlines, when the warnings from the FDA weren't really that bad.  In addition, the warnings about liver problems (the one you hear about in all those TV commercials) were actually downgraded. 

2. It is not entirely the media's fault.  The FDA does a very poor job when releasing information.  When they update something, they should make it clear to physicians and patients what the real risk is.  Once again, the FDA failed miserably.

3. Statins are probably some of the safest medications we have. If patients could easily perform and interpret their own blood work, these might even be over the counter.  Some have suggested that this might be a good idea. Moreover, statins reduce heart attacks and strokes (#1 and #4 killer in the US). Though no medication is perfectly safe, I can think of no other long term medication where the risk benefit ratio is so far in favor of the drug. Cardiologist John Mandrola put this best in his post (via KevinMD) "Let's close the chapter on statin safety." 

Ok, now for the details. 

Today the FDA released information that they were updating warning information on statins. Essentially, there are three areas where safety data was updated: liver enzymes, memory impairment and diabetes.

Liver enzymes- This one is actually good news. Earlier statins caused some elevations in liver enzymes which were feared to potentially cause liver damage.  After many years of usage, it doesn't seem this fear is warranted.  Because they can affect the liver, patients with pre-existing liver disease should use statins cautiously. Even though statins can cause liver enzyme elevation, it is usually at the highest doses and usually returns to normal when the statin is stopped of the dosage is lowered. The routine monitoring of liver enzymes that was once recommended is now no longer required. 

Memory Loss- This is the one that makes me the most annoyed. First, because it really isn't true and second because the way the FDA communicated the data is useless at best and harmful at worst, since patients may stop taking statins because they are afraid that they will get Alzheimer's. 

According to the release the

"FDA reviewed the AERS database, the published medical literature (case reports and observational studies),^4-13 and randomized clinical trials to evaluate the effect of statins on cognition.^14-17"  

The numbers above refer to references of studies they looked at. However, of the 13 studies they analyzed "did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline." In fact, most of these studies were looking at use of statins to PREVENT Alzheimer's. Thus, most of the data they used to make this recommendation was from their own AERS database.  It would have been really nice to release this data! However, one of the mentioned publications did look at MedWatch drug surveillance system of the Food and Drug Administration (FDA) from November 1997–February 2002 for reports of statin-associated memory loss.  Of course we don't know the exact number of patients that took a statin during those 5 years, but it was in the millions.  The authors were only able to find 60 reports, of which none was truly confirmed (just patient report) and more than half noted improvement when the statin was stopped. 

I have previously blogged about this issue back in 2008 in my post Lipitor and Memory Loss as well as another post Lipitor: Responding to Spacedoc. Spacedoc is really Dr. Duane Graveline, MD, MPH, a family physician who became a NASA's scientist, but is better known for his book "Lipitor, Thief of Memory" which he wrote after having two episodes of something called transient global amnesia (TGA) which he states was associated with his use of Lipitor from 1999 - 2000. In fact, I actually became aware of TGA because the mother of a close friend had the exact same thing. 

Bottom Line- There may be some connection between Lipitor and memory loss. However, even if there is, it is extremely rare (you have a better chance of winning the lottery) and even if you get it, it usually goes away if you stop the medication. In other words, there is absolutely no reason to be alarmed, and no reason not to take the drug if you need it to control your cholesterol. 

Diabetes- This is another topic that I have blogged about, and one that seems not to want to go away.  You can see my post "Statins Don't Cause Diabetes" for all the details.  Much of the concern came from a Crestor trial which actually showed Crestor to cut heart attack risk in half in patients that had relatively normal cholesterol.  This study used a particularly high dose of Crestor, and the FDA warnings point to other studies using high dose statins with similar findings.  It is important to note that in the Crestor study, about 40% of the patients were at risk for developing diabetes in the first place, that measures of diabetes in the study were really no different, but the physician reported (i.e. unconfirmed) rates of diabetes were increased.   However, more importantly, if you look at the actual rates of developing diabetes it was 3% in the Crestor group an  2.4% in the placebo group.  In other words, if statins increase your risk of developing diabetes, it increases it only by 6/10 of a percent (not as low a winning the lottery/memory loss, but pretty darn low). However, with millions taking a statin, even a small risk is something to consider.  However, one must also note that diabetes is a disease process more than just an isolated sugar number, and it is unclear what actual risk a statin would cause by turning a pre-diabetic patient into a diabetic one.  In fact, patients who are pre-diabetic have a 4 to 6 times greater risk of heart attacks and strokes, and statins have been used in pre-diabetic patients and shown to reduce their risk of heart attack and strokes.  Conversely, no study has shown that reducing sugar in a diabetic reduces their risk of heart attack and stroke. 


Bottom Line-statins may raise your sugar a tiny bit, and for those patients who are at risk for developing diabetes, taking a high dose statin may "push" that patient into having diabetes sooner than expected.  However, even in that circumstance, the statin is probably still well worth the risk since it is potentially preventing a heart attack or stroke and slightly increasing the sugar probably has no clinical ramifications. 

Statins and Prostate Cancer

The Wall Street Journal is reporting on a study published in the journal Cancer, and described by Reuters that links statins to reducing the risk of prostate cancer.  According to the report:

The researchers found that men who died of prostate cancer were half as likely to have taken a statin at any time, and for any duration, than men in the "control" group.  Those with fatal cancers were 63 percent less likely to have ever taken a statin, according to findings published in Cancer.

 I would love for statins to reduce the risk of prostate cancer. Readers of this blog know I am relatively pro-statin, in the right patient population. However, this study is too limited to make an actual connection, and I would not recommend taking statins solely for prostate cancer prevention.

What did the researchers do? The looked at the medical records of 380 men who died of prostate cancer and matched them with the records of another 380 men who did not have prostate cancer.  They use statistical techniques to adjust for difference such as age, weight and other medications.

What's the problem with the study? First, if the study findings are correct, such a study that uses medical  records and then looks back in time can not prove causation.  It only proves association.  This means that the study doesn't prove that taking a statin will ward off prostate cancer. Rather, the results mean that men who had died of prostate cancer were less likely to take a statin.  This is a big difference.  There are multiple examples where a confirmed association did not result into a confirmed causation (Vitamin E/C and  Folic Acid for preventing heart attacks).  In addition, there are many reasons that the association is in fact not correct.  Perhaps men who had been diagnosed with prostate cancer chose not to take statins, even if their doctors recommended it, because they were more concerned about the prostate cancer?  Perhaps men who did not have prostate cancer were extremely health conscious and were more aggressive about both doing things to prevent cancer (exercise, diet, etc.) as well as being more aggressive about  taking statin medications for high cholesterol?

Why this might be true? The only way to truly determine causation is to perform a randomized clinical trial (RCT).  Only a RCT can both eliminate some of the confounding variables (i.e. were the men without prostate cancer more aggressive about their overall health) and demonstrate the primary ingredient for causation: that exposure always precedes the outcome.  If factor "A" is believed to cause a disease,  then it is clear that factor "A" must necessarily always precede the occurrence of the disease. 

However, there are two findings from this study that support causation.  First, is dose-response relationship.  Only the newer, more potent statins showed benefit. Taking a lower potency statin was not protective.  The second is biologic plausibility. According to the Reuters report, Dr. Stephen Freedland, who studies prostate cancer at the Duke University Medical Center in Durham, but wasn't involved in the new study was quoted as stating that statins may protect against fatal prostate cancer through their known cholesterol-lowering effects, mentioning that cholesterol is a "key nutrient" for cancer cells, so lower cholesterol levels in the body could prevent more aggressive forms of cancer from developing.

Bottom Line: This study is exciting and will hopefully lead to randomized trials which can prove whether or not taking a statin will prevent prostate cancer.  For now, there is very limited evidence to suggest this would actually work, and men should not start taking a statin just to lower their risk of prostate cancer.

Disappointing Results for Crestor

In my recent post All in for Crestor, I discussed how the SATURN study comparing Crestor to Lipitor was likely a make or break study for AstraZenca's cholesterol pill.  As mentioned, because Lipitor will soon go generic in November, AZ needed to give insurance companies a reason to pay for the more expensive branded pill, then the soon to be generic and cheaper version of Lipitor, which has been the number one selling drug in the country.

As reported in Pharmalot's post Disappointing Crestor Results For AstraZeneca (see the official AstraZeneca statement here ), the just released results of SATURN show that the 40mg dose of Crestor was numerically but not statistically significantly better and reducing plaque build up (as measured by % change) as the 80mg dose of Lipitor.  As secondary measure, plaque buildup as measured by volume was statistically significant, but since this was not the primary outcome of the study, it is likely enough for insurers to give Crestor a favorable status on their formulary lists.


Bottom Line: Crestor is a great drug.  It reduces LDL better than Lipitor.  We know that from outcome studies of all statins, that the lower the LDL with a statin, the more you decrease heart attacks and strokes.  In addition, despite it's potency, it has very good tolerability.  Certain patients that might need 80mg of Lipitor, might not be able to tolerate side effects at that high of a dose, and might end up doing better on 20mg or 40mg of Crestor.  That said, starting in 2012, unless AZ cuts the price on Crestor drastically, it may be a challenge to get the prescription approved for patients. 

All In For Crestor

The American Heart Association will be holding its annual meeting this November.  Cardiobrief.org just posted the announced "late-breaking" clinical trials. These are the big name trials that usually grab a lot of headlines. One of the trials is the AIM-HIGH trial which showed that Niacian didn't really do much in patients whose bad cholesterol or LDL was controlled with a statin (see my post What to do about Niacin? )
Another very important study will also be presented that same November 15th, 2011: Comparison of the Progression of Coronary Atherosclerosis for Two High Efficacy Statin Regimens with Different HDL Effects: SATURN Study Results.  The SATURN study is the Astra Zeneca (makers of Crestor) study comparing high dose Crestor (40mg) with high dose Lipitor (80mg).

Patients in the SATURN study will have known cardiac disease as indicated by a need for coronary angiography (angiogram) and angiographic evidence of coronary disease.  The main end point is  is IVUS-assessed change in the percent atheroma volume in a >40-mm segment of a single coronary artery; which is a "doctor" way of saying they are going to look for plaque build up in the artery.  This is the same end point used in the famous (or infamous) ENHANCE trial which showed that adding Zetia to simvastatin (zetia + simvastatin = Vytorin) did absolutely nothing to plaque build up ( Vytorin and Zetia: What to do now? )

What's interesting about SATURN is that the LDL lowering properties of the highest doses of Crestor and Lipitor are about the same.  However, at those doses Crestor raises the HDL or good cholesterol by about 8% where Lipitor only raises HDL by 3%.  Other studies have shown that plaque build up in the arteries (atherosclerosis) that causes heart attacks and strokes, is not just about LDL, but also about HDL.  Other studies looking at high doses of Crestor when compared to placebo show that it can prevent plaque build up and possibly even lead to regression.  The Lipitor data on this is less robust.

The timing of the results at the AHA is particularly interesting, since it will coincide with Lipitor going generic.  Zocor or simvastatin has been generic for a while, and works well in many patients.  However, patients requiring more aggressive reduction in their cholesterol will not meet their goals on simvastatin and high dose simvastatin is associated with side effects, which prompted a recent FDA warning. (See Don't Take High Dose Simvastatin). Thus, the need for a generic potent statin like Lipitor is huge.  However, this could mean that insurers will make it very, very difficult for patients to get Crestor.  UNLESS......... SATURN proves that high dose Crestor compared to high dose Lipitor significant reduces plaque build up in high risk patients.
Therefore, the SATURN trial is really a huge gamble for Astra Zeneca.  When Merck's ENHANCE trial showed that Vytorin didn't really do more than the generic statin, prescribing rates dropped precipitously. Crestor likely faces the same fate is SATURN turns out to be a negative study.

Why OTC Lipitor is a Bad Idea

As reported by the Wall Street Journal, Pfizer, the maker of one the best selling drugs ever, is trying to get the FDA to approve an Over the Counter (OTC) version of their blockbuster Lipitor, not coincidentally on the eve of Lipitor going generic.
Readers of this blog know that I am a big proponent of cholesterol lowering medications like Lipitor (statins) for patients at moderate to high risk of cardiovascular disease.  In particular, I am a fan of the more potent statins like Lipitor and Crestor, because of their increased efficacy with fewer side effects (see Don't Take High Dose Simvastatin).  Finally having a generic version available of Lipitor will be a great thing for many patients.

That said, making Lipitor OTC is a bad move. First, there is a difference between medications like Prilosec and Claritin that have gone over the counter and Lipitor.  Diagnosis for GERD and allergic rhinitis for which those medications respectively treat are made mostly on symptoms alone.  Patients don't need to go to medical school to suspect that they may suffer from heart burn or allergies. Starting treatment without seeing a physician is actually medically sound because more often then not the medications will relieve symptoms avoiding a physician office visit.  In contrast, starting a patient on a statin is much more tricky.  Patients need to know their individual risk for cardiovascular disease.  Though there are tools available online to determine this (I use the NIH's risk calculator daily in my clinic), determining individual risk of disease, benefit of taking a medication and weighing this against potential side effects is best decided by a discussion between a doctor and patient. Secondly, before starting a statin medication, one needs to know their cholesterol levels.  Though there are other methods (health fairs, work screenings) of determining cholesterol levels, getting a blood test usually requires a visit to the doctor's office. In addition, follow up blood work (checking for medication efficacy, liver side effects) is warranted after starting treatment. Thus, the benefit of having a medication OTC is negated.  Finally, Claritin and Prilosec are very safe.  They are as safe or safer then other OTC medications.  Lipitor is also very safe, but is associated with rare, but serious side effects.  Taking Lipitor OTC without consultation with a physician creates the risks of patients developing these side effects without proper warnings and therefore potentially worse outcomes if attention is not sought.

The second main reason that OTC Lipitor is a bad idea is that it will hurt more patients than it will help.  The reason for this is that when a medication goes OTC, insurance companies usually will not pay for them.  Now that Allegra is over the counter, it is virtually impossible for any of my patients to get a prescription version antihistamine.  Though they can easily get this OTC, not having a prescription means they need to pay for it out of pocket.  The cost of an OTC medication, even if the generic OTC version is used, is generally more than the co-pay for a generic prescription.  It is unlikely that generic Lipitor will make the $4 Walmart or Target list, but after six month, the co-pay for generic Lipitor would still likely cost a lot less for most patients then paying for OTC Lipitor out-of-pocket. 

Bottom Line: The reason why Pfizer wants Lipitor OTC is for one reason: to make more money.  They can argue that cardiovascular disease is the number one killer in the US, and by having Lipitor OTC, it will be available to more patients.  However, because statins require blood work and medical consultations, the risk of harm to patients outweighs the potential benefits of greater availability.  In addition, this will result in cost-shifting to patients in order to boost Pfizer's profits. Hopefully, the FDA will say what they said when Merk tried to pull this off: "No."

Don't Take High Dose Simvastatin!

Today the FDA just announced a new warning on the highest dose of simvastatin, the most popular cholesterol medication prescription in the country.  They have issued this warning because "the highest approved dose--80 milligram (mg)--has been associated with an elevated risk of muscle injury or myopathy, particularly during the first 12 months of use."
The current recommendation is not to start simvastatin at 80mg and only to continue taking the 80mg if you "have been taking this dose for 12 months or more and have not experienced any muscle toxicity. It should not be prescribed to new patients.

First, why is this announcement so important.

As Forbes' Matthew Herper points out in A Snapshot Of The Cholesterol Drug Market, though Lipitor is the biggest selling drug in terms of dollars, generic simvastatin is actually the most commonly prescribed cholesterol lowering  medication.  As you can see from the graph below (viewed much better on the Forbes site), once Zocor became available as generic simvastatin, it became the most popular statin written (blue line) whereas Lipitor (red line) prescriptions continue to tumble. Over time, insurance companies have made it more and more difficult to write for any branded statin by increasing co-pays for patients or increasing hurdles to get prescriptions approved.

In fact, simvastatin makes sense for many patients.  Most data suggest that benefit is derived from statins when they reach about a 30% reduction in bad cholesterol, or LDL.  The folks at the NIH's NHLBI have evaluated the efficacy of all the available statins (see below) and you can see that most statins will achieve that goal at various doses.  For example 10mg of atorvastatin (Lipitor), 20-40mg of simvastatin, and 5mg of rosuvastatin (Crestor) all lower LDL cholesterol by about the same amount.  Thus, if you just need a 30% reduction in LDL, you should be fine with the generic.  Problem is that many patients need more than that amount of reduction.  Thus, if you want to stick to a generic, you would have to go to 80mg of simvastatin.


Now one might thing that the stronger, more potent the statin, the more likely it is to cause side effects.  Turns out the opposite is true.  The graph below shows that when plotting LDL reduction against number of patients developing myopathy (what the FDA is concerned about), it seems like the more potent statins (Crestor, Lipitor) not only lower cholesterol better, but have a lower risk of myopathy. Myopathy is pretty uncommon, usually only about 1/10,000 or 0.01%. Looking at both Lipitor and Crestor, you can see as the dose goes up (10, 20, 40, 80) the percent of reduction of LDL continues to improve, but rate of myopathy is pretty much the same except for a slight bump at the 80mg dose of Lipitor.  (Though not on the graph, you can see why the 80 mg dose of Crestor wasn't approved, because at that dose there was significant myopathy). However, when you jump from 40-80 mg of simvastatin, the LDL only goes up a few points, but the rate of myopathy skyrockets to over 1% (that's 1/100 instead of 1/10,000).  Finally, you can why cerivastatin or Baycol was pulled from the market.  It was pretty weak at lowering LDL, but had up to 2% incidence of myopathy at the higher doses.




The good news is that Lipitor will go generic in only a few months.  When that happens, I am sure that the graph above will change drastically.  All Lipitor scripts will likely go to the generic medication and probably many of the simvastatin prescriptions will also switch to generic atorvastin, since it is a better statin (more potent, fewer side effects).  Crestor is another option (most effective, fewest side effects), but will not go generic for a while. The other thing to note is that Pfizer, who is about to lose Lipitor, is trying to get as much business as it can by offering patient coupons, so that (as long as you are not on Medicare part D or Medicaid) a prescription of Lipitor will only cost you $4 until it goes generic. 

Bottom Line: All statins are not created equal and generic is not always best.  If you are on Simvastatin 80mg, you should seriously discuss with your doctor about switching.  In fact, if you are on simvastatin at any dose and not on Medicare part D or Medicaid, but have commercial insurance, you should consider asking your doctor about switching to Lipitor with the $4 coupon (you may actually save money by NOT taking the generic) until it too goes generic.

What to do about Niacin?

I have been getting a lot of questions regarding the use of Niacin since the media recently reported that the NIH had stopped their AIM-HIGH study. AIM-HIGH was designed to see if adding Niacin to patients on a statin who still had low HDL and high triglycerides would improve cardiovascular outcomes (heart attacks, strokes). Though we know that high triglycerides and low HDL are both strongly associated with heart disease, that Niacin will raise HDL and lower triglycerides and even few early studies did show raising the HDL with Niacin did work; this large, randomized NIH sponsored showed no evidence of improvement.  Though the actual data from the study has not been released, we do know that the NIH stopped the study a year early because there was no benefit seen and possibly some harm in the form of excess stroke.  One possibility is that patients were taking statins at doses that lowered their LDL to very aggressive levels (target range of 40-80). Some have postulated that with an LDL that low, you will never get a heart attack or stroke.  So, Niacin may indeed work, but not with super reductions of LDL's with statins.


One of the main points of from these findings is that we have to be careful when it comes to using surrogate endpoints (like LDL and HDL) for treatment.  For example, lowering the LDL with a statin reduces heart attacks and strokes. However, lowering the LDL with ezetimibe (Zetia) doesn't seem to do this (see here for more details)  This might be the case for Niacin and HDL as well. 

I have never been a big fan of Niacin because it causes pretty bad flushing, increases uric acid/gout, and most importantly raises blood glucose.  Most of my patients are diabetic/prediabetic, so raising their blood sugar is not something I am too fond of.  The other drugs that can raise HDL and lower triglycerides are fibrates. Gemfibrozil has clearly demonstrated this in a large VA study (VA-HIT).  The problem with gemfibrozil is that it can interact with statins, causing some serious side effects.  Statins are the one med that clearly works in just about everyone with increased cardiac risk.  Fenofibrate works the same way, but can be used safely with a statin.  However, when they tried to demonstrate cardiovascular improvements with fenofibrate (FIELD study), the primary outcome was not statistically significant.  One of the differences between VA-HIT and FIELD is that more patients were on statins in FIELD, since FIELD was a more recent study and regular use of statins had become standard of care.  However, in the diabetic patients with low HDL and high triglycerides, the FIELD study did show that fenofibrate reduced heart attacks and strokes. The ACCORD lipid study (another large, randomized, NIH sponsored trial), attempted to prove benefit by adding fenofibrate to all diabetics on a statin, but failed.  However, similar to FIELD, in those diabetics with low HDL and high triglycerides, fenofibrate added to a statin did reduce heart attacks and strokes. The consistency of these findings therefore have some merit. 

Bottom Line: Statins remain the first choice for patients at increased cardiovascular risk and should be used at doses that meet individual LDL goals and/or lower LDL by 30-40%.  After that, the rationale for treating low HDL/high trigs is now less clear. Before we see the actual data from the AIM-HIGH study, it would be premature to pull all patients off of Niacin.  That being said, in my opinion, Niacin's days are likely numbered.  Evidence for raising HDL and lowering triglycerides seems to be much stronger for fenofibrate, at least in diabetics, and fenofibrate does not seem to have the negative effects, specifically hyperglycemia, seen with Niacin. 

Lipitor or Crestor for LDL's above 160

I just read A systematic review and meta-analysis on the therapeutic equivalence of statins. This artilce will not make any major U.S. headlines because it is a Taiwanese study from a not very well known journal. However, the methodology is sound and makes an important point to patients who need a statin and are deciding between a generic and more expensive brand name medication.

The study did a systematic review of all the studies which compared the different statins. They found that at comparable doses, statins are therapeutically equivalent in reducing LDL (or bad cholesterol). This would suggest that if statins are essentially equal, provided you use the right dose, then you should always go with a generic. However, the other thing they found was that "the only two statins that could reduce LDL-C more than 40% were rosuvastatin and atorvastatin at a daily dose of 20 mg or higher." In other words, those patients who need cholesterol lowering drugs and have to get their cholesterol down by less than 40% should be OK with generic, but those who need to get their LDL cholesterol by more than 40% should use either Crestor (rosuvastatin) or Lipitor (atorvastain). Though new guidelines should be out by the end of the year, current guidelines suggest that patients with increased risk for heart attack and stroke (all diabetics, mulitple risk factors,etc.), who are generally the patients we use statins in, need their LDL's under 100. This means that if you are at increased risk for heart attack and stroke, and your LDL is 160 or above, you should not take the generic (even if it is cheaper), but take the more expensive branded cholesterol medicines.
Fortunately, as I mentioned in a recent post Are Drug Reps and Free Samples Bad For Patients? It Depends, both companies offer coupons to offset the additional out of pocket costs, so you should not pay much more for Crestor or Lipitor than what you would pay for a generic medication.

Pharma Should Not Settle Off-Label Promotional Suits

Major headlines were made when it was announced that AstraZeneca Settles Case Over Marketing of a Drug For $520 Million. This is not the first and will not likely be the last off-label settlement by a drug company. The charges from the Justice Department , which the company denies, claim that Astra Zeneca (from Med Page Today) paid doctors for "ghostwritten journal articles that the named authors did not write and reported studies they did not conduct" and "to give promotional lectures to other health care professionals about unapproved and unaccepted uses" for their drug Seroquel (quetiapine) which is used to treat bipolar disorder. Though ghost written articles may not be the best way to promote your product, they are not illegal. In addition, paying physicians to speak about a product is an FDA approved way for drug companies to discuss their products with practicing providers. These activities were not the problem, its that (the Justice Department claims) they were off-label, not on label promotions.

I blogged about what is meant by labeling a while ago in a post called An Indication For Change. Briefly, a physician can prescribe any FDA approved drug for any reason they want. However, a drug company can only promote (sell) that drug for what the FDA says it can be used for. A great example would be Crestor. Back in November of 2008, I blogged about the results of the Jupiter trial (see Jupiter is Out, and the News is Good! ), which showed that in patients who had relatively normal cholesterol levels but high CRP levels, 20mg of Crestor reduced the risk of heart-related death, heart attacks and other serious cardiac problems by 44%. This was a large, randomized clinical trial with important information and the first real trial showing major benefit when a statin was used as primary prevention for heart disease in people with normal cholesterol levels. Despite the exciting news, the Crestor drug reps couldn't talk about it, even though the study was published, and the results were headlines in every major media outlet. This would have been considered off-label promotion. It wasn't until February 2010, when Crestor was approved for primary prevention of cardiovascular disease by the FDA.

I will admit that I do not write Seroquel, and told many of the AZ drug reps who tried to get me to use this drug, that Seroquel was not really a primary care drug, and they would be better off spending their time speaking with the psychiatrists. However, though I am certain one or two rogue drug reps probably bent the rules here and there, given the previous large settlements by other drug companies, I find it very hard to believe that AZ systematically promoted Seroquel for off-label use. As stated AZ denies these claims.

If this is indeed the case, then I believe AZ should fight the claims by the Justice Department, rather than just pay a fine. If you are really innocent, then you will try to prove your innocence at any cost.

As a physician, I understand what settling a case means. The vast majority of malpractice claims are settled. This is because doctors get nervous when their fate is left to a jury to decide between the rich doctor and the injured patient. For physicians, especially given the cost of litigation, it often makes more sense to settle, admitting no wrong, and get on with your practice then to prove your innocence. However, with pharma's deep pockets, cost should not be an issue. Every time a drug company settles a claim for off label promotion, it is saying to patients and physicians "we are not to be trusted." As part of their settlement, AZ will likely have to send "Dear Doctor" letters to all physicians essentially admitting guilt.

Interestingly, The Wall Street Journal is reporting in a post Whistleblower Twice Over: First Lilly, Now AstraZeneca, that the same person who reported AZ to the government (and will pocket $45 million) previously blew the whistle on Eli Lilly who settled a $1.4 billion for off label promotion (he pocketed up to $100 million for that). The fact that the same person blew the whistle on two companies for the same charge (in my mind) calls the entire off-label promotion scheme into question.

This will not be the last big settlement for off-label promotion. The government makes big bucks on these cases, and the drug companies just write a check when fined. If pharma really want to show physicians, patients and the public that it is just trying to make useful medications to help people and not trying to make a profit any way they can, they should fight these claims as hard as possible.

Blood sugar, high blood pressure and cholesterol control still important for diabetics.

The secondary findings of the ACCORD trial reported out today, and already the media is buzzing. Though the news was disappointing, the results are not nearly as bad as some of the media headlines are making it out to be. ABC News is reporting: ACCORD Study: Cholesterol, BP Control Does Little Good for Diabetics and MSNBC states that Intense treatment hopes for diabetics dashed. If I were a diabetic, I might think that controlling blood pressure and cholesterol was not important. However, this couldn't be further from the truth.

The same thing happened when the media first reported that the ACCORD study was stopped.
( See ACCORD and ADVANCE: Good News for Type 2 diabetes...really). This first part of the study was looking at whether or not intense lowering of blood sugar to normal (A1c less than 6%) prevented heart attacks and strokes more than the current standard of care (A1c less than 7%) which had not proven to reduce heart attacks or strokes. The study was stopped early because there were more heart attacks and deaths in the intense group. However, though the media headlines similarly questioned the role of blood sugar control back then, the good news was that the rate of heart attacks and strokes were much lower than expected. In other words, good sugar control in diabetics is likely important in preventing cardiovascular disease; however, intensely lowering blood sugar is probably not a good idea.



What was reported today at the American College of Cardiology meeting was the blood pressure and cholesterol arms of the study. The blood pressure arm similarly looked at getting the blood pressure to normal (120/80) compared to standard care. Again, both groups had fewer heart attacks and strokes than expected. Thus, blood pressure control is important, just not continuing to add medicines until the BP is normal. The cholesterol arm of the study looked at something different. All the patients were given statins, but half were randomized to fenofibrate, a different kind of cholesterol medicine that doesn't affect bad cholesterol too much (LDL), but does raise good cholesterol (HDL) and lowers fats (triglycerides). Unfortunately, there was no difference in heart attacks or strokes in either group. However, when you looked at diabetics with low HDL and high triglycerides, there was an improvement. In other words, unlike statins which should be given to every diabetic, fibrates should be used only in diabetics with low HDL and high triglycerides. Again, this reinforces the importance of cholesterol lowering in diabetics, despite what the headlines may read.

Bottom Line: If you are a diabetic, try and keep your A1c under 7%, and don't take any more medicines (especially insulin) to try to get the A1c any lower. Blood pressure and cholesterol control are also very important. Diabetics should keep the blood pressure under 130/80, but don't need to keep adding medications to get it perfect (under 120/80). All diabetics should take a statin medications (regardless of LDL number), and if your triglycerides are above 200 and HDL is below 35, add a fibrate to the statin.

Should all patients with metabolic syndrome or elevated HgA1c take statins?

Metabolic syndrome is a constellation of factors (increased waist circumference, high blood pressure, elevated fasting glucose, high triglycerides, low hdl) that are associated with increased cardiovascular risk. Metabolic syndrome is often called pre-diabetes both because sugars are high and because metabolic syndrome is related to insulin resistance, the primary mechanism of type 2 diabetes. Diabetes has been generally defined as having a fasting blood sugar of greater than 126, so patients with sugars between 100-125 have also been called pre-diabetics. Like diabetes, we know that metabolic syndrome is associated with increased cardiovascular risk (increased risk for heart attack and stroke). Men with three or more components of metabolic syndrome have more than double the risk for cardiovascular disease, and women with three or more factors have almost six times the risk for cardiovascular disease.

Because diabetes is associated with such a high cardiovascular risk, and because lowering cholesterol with statins in diabetics has proven to reduce these events, current guidelines recommend that virtually all diabetics take a statin, even for those patients with normal cholesterol levels. One question which remains is whether the same should be done for patients with elevated fasting blood sugars and/or metabolic syndrome.

A recent study in the New England Journal called Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults may give us more reason to consider thinking about using cholesterol lowering agents in patients with elevated blood sugars, even if the cholesterol is normal. The study looked at the relationship of hemoglobin A1c (HbA1c) to development of diabetes and cardiovascular risk. It was not surprising that even high end normal HbA1c's predicted development of diabetes, but what was surprising was that high normal HbA1c was strongly associated with risk for heart attack and stroke.

In the study, patients with an HbA1c of less than 5.0% had 4% relative decreased risk of cardiovascular disease compared to patients with and A1c of 5.0 to 5.5%. However, those with A1c's from 5.5 to 6.0% had a 23% increase, those with A1cs of 6.0 to 6.5% had a 78% increased risk, and those with 6.5% or greater had an almost double risk of cardiovascular disease. This suggest a strong correlation between elevated blood sugar (pre-diabetic patients) and cardiovascular risk.

In the most recent updates to the ADA guidlines published in the January 2010 edition of Diabetes Care, the ADA now defines diabetes as patients with an A1c of >6.5%, and those patients with A1c's between 5.7–6.4% have been included in a category of increased risk for future diabetes. Thus, the last group in the recent study would now be considered to already have diabetes.

This study also made me think of the JUPITER trial. The JUPITER trial is a controversial trial which I have blogged about before (see Jupiter is Out, and the News is Good! and Crestor: Get Ready to Ask Your Doctor for the CRP Test). It showed that patients with relatively normal cholesterol levels, but high levels of CRP benefited from taking 20mg of Crestor. Crestor now has an FDA indication for primary prevention of heart disease.

Interestingly in the JUPITER study, 41% of patients had the metabolic syndrome. The median A1c was 5.7 (interquartile range was 5.4-5.9). This means that about half the patients in the study had an extra 23% increase for cardiovascular disease based on A1c alone, and about 25% of patients had a 78% additional risk or higher (with the new ADA definition, there was probably not an insignificant number of patients in the JUPITER study that had an A1c above 6.5% that would now be considered to be diabetic and should have been on a statin). The reason I bring up JUPITER is because we now have a primary prevention trial in which a substantial number of patients had metabolic syndrome or elevated sugar, and this trial showed that statins were beneficial.

Thus, there are compelling arguments that can be made to suggest that patients with either metabolic syndrome or an elevated HgA1c should be on a statin (similar to diabetics) regardless of their cholesterol number.

However........
1. In order to definitively make this case, you would need a large, randomized clinical trial of patients with metabolic syndrome (or A1c's between 5.5 and 6.5) and normal cholesterol, randomized to statin or no statin. I am hopeful that the NIH or some drug company is planning on doing this.
2. In a subgroup analysis of the JUPITER trial, the investigators looked to see whether metabolic syndrome was a factor in those patients that benefited from Crestor and didn't find a statistically significant difference. It appears that CRP levels and not sugar levels is what made the difference.
3. Though the presence of metabolic syndrome does predict cardiovascular disease, it predicts diabetes much better, and the Framingham risk score is a much better predictor of cardiovascular disease (see Metabolic Syndrome vs Framingham Risk Score for Prediction of Coronary Heart Disease, Stroke, and Type 2 Diabetes Mellitus )

Bottom Line: Elevated HgA1c levels and metabolic syndrome substantially increase risk for cardiovascular disease, and there are compelling reasons to consider statin therapy in these patients, though conclusive data is lacking. As per the new ADA guidelines, patients at risk for diabetes should be screened with a HgA1c, and if it is greater than 6.5%, these patients are now considered diabetic and should receive a statin.

Since the Framingham risk calculation is still the best predictor for cardiovascular risk, a reasonable approach might be to adjust the Framingham score for patients with HgA1c's between 5.5% and 6.5%. Currently, patients with a Framingham risk of greater than 10% are considered for more aggressive LDL goals (which usually means they need a statin). Based on the numbers from the recent New England Journal study, for patients with A1c's from 5.5 to 6.0%, more aggressive goals should be considered when these patients have a Framingham score of 8% (instead of 10%), and for those with A1cs of 6.0 to 6.5%, more aggressive goals should be considered for a Framingham score above 6%.

Statins Don't Cause Diabetes

As of this morning, the only major source reporting the results of a recent study from Lancet is Business Week. However, the headlines that will likely pop up in the next few hours will likely be similar to theirs: "Cholesterol-Cutting Drugs Raise Diabetes Risk by 9% in Study." In my last post I discussed how the media likes bad news stories, so even though this is not yet all over the headlines, I will take a preemptive strike for potentially concerned patients.
The Lancet study is a large major meta-analysis of major statin trials, looking to see if there is a risk associated with statins and the development of diabetes.

The authors likely got the idea to do a meta-analysis from the JUPITER trial which showed that Crestor reduced heart attacks in patients who wouldn't have generally gotten a statin, except they had an elevated CRP (see Crestor: Get Ready to Ask Your Doctor for the CRP Test. ) One thing seen in this study was a potential increased risk of the development of diabetes. I mentioned this in my blog post when the data was first released that physician report of diabetes was increased in the Crestor group (270 reports of diabetes, vs. 216 in the placebo group; P=0.01). I stated that though one might be concerned about this, these were physician reports without confirmation. When looking at the study lab values in Jupiter, there were no significant differences with respect to the fasting blood glucose level, and the A1c level was pretty much the same (5.9% and 5.8%). I also mentioned that there was no biologically plausible reason to suspect Crestor, or any statin, as a cause of diabetes. In addition, both groups of patients in the JUPITER study had a 41% prevalence of metabolic syndrome, which is a pre-diabetic state. Therefore it should not have been surprising to find an increase in diabetes in both groups.

The meta-analysis looked at Jupiter and several other studies combined and found a 9% increase in the development of diabetes in patients taking statins.
So if this is true, how can you say that statins don't cause diabetes????
1. The 9% value is a relative risk, not an absolute risk. If 1/100 patients taking placebo have a side effect, and 2/100 patients taking a statin have a side effect, the relative risk increase is a doubling or 100%, but the real or absolute risk is only 1%. Drug companies and the media (and unfortunately some authors, as was the case in this study) like to talk about relative risk instead of absolute risk, because it makes there drug/data/news story look better. In this study, the actual increase in diabetes was 0.38% or about one third of 1%. Even though the result is statistically significant (true by scientific standards), the magnitude of the increase is so small that there is a high possibility that this is not true.
2. The study is a meta-analysis, which by design can not prove causation. The only way to really find this out is to do a large, randomized controlled study to specifically look at whether or not statins cause diabetes. This will never happen because 1) given the low absolute risk, the number of patients needed in this study would be tens to hundreds of thousands, which means the study would be ridiculously expensive and 2) with Lipitor going generic, no drug company is going to fund such a study. I spoke of the dangers of meta-analysis many times, specifically in talking about Nissen's meta-analysis of Avandia (multiple posts on this). Even in Nissen's own meta-analysis showing a "40% increase in heart attacks" in patients taking Avandia (relative risk), there was really NO DIFFERENCE in the absolute risk in his study! Of course that didn't stop the press, and millions of patients stopped taking Avandia. Unlike the randomized, controlled trial for statins and diabetes we will never see, there was a randomized controlled trial on cardiac safety and Avandia called the RECORD trial which was presented at the ADA this past summer. It showed NO RISK of heart attacks with Avandia. Don't be surprised if you never hear about this, since the press does not seem to be too fond of reporting good news.
3. As above, there is no biologic reason to believe that a statin medication would cause diabetes.

In other words, what you are seeing in the headlines is statistical garbage, that really doesn't mean anything. An incredibly low absolute risk found in a meta-analysis without a biologic reason to support a connection between statins and diabetes should not be cause for concern.

Bad cholesterol not that bad? Shame on MSNBC...Again!

When it comes to politics, I do like MSNBC. They are also not bad in delivering the headlines. However, when it comes to health, especially on their web site, they have a long way to go. I am particularly dismayed at their re-purposing of material from other sources. This strategy, used by many other reputable web sites is not in and of itself horrible, but when it comes to health, I am not sure that their editors even read the articles they are posting as their own! This is especially true of material that the post from Men's Health. I mentioned this a while back in my post The truth on the 8 drugs doctors wouldn't take . This was a horrible article that was re-purposed on MSNBC about drugs that were supposedly so dangerous, doctors wouldn't take them. In fact, the authors of the article never asked one doctor when writing this article. I actually did (via Sermo), and found that 7 of the 8 drugs mentioned, most doctors had no problems prescribing.
Now Men's Health is back to their usual scare tactics in an article called "Bad cholesterol: It’s not what you think" which is now a featured article on MSNBC.

Factually, there is nothing wrong with the article. The major point of the article is that the concept of LDL cholesterol being "bad" is oversimplified. In fact, certain LDL particles may actually not be that harmful, whereas other types of LDL cholesterol can be killers. Fortunately, newer technology is becoming more readily available, which may help us customize treatment more accurately.

The problem that I have is the inflammatory language they use, calling the LDL "hypothesis"
"the greatest medical misadventure of our time" One of the paragraphs states that "the LDL hypothesis has also encouraged many of us to swallow the most-prescribed class of drugs in recent history. Americans spent more than $14 billion on LDL-lowering medications in 2008. Whether that money came out of their own pockets — straight up, or through ever-escalating co-pays — or out of the hemorrhaging U.S. health-insurance system known as Medicare, it's a huge expenditure. " In fact, the subtitle of the original article, which is not posted on MSNBC states, "before you swallow what your doctor prescribes, we suggest you read this article." They make it sound like doctors and the medical establishment have duped patients into taking unnecessary and expensive medicines.

With multiple drug advertisements on TV and blame being pointed at drug companies for our rising health care costs, it is not surprising that many people would find this "information" yet another reason not to take medications. The problem with this type of "journalism" is that it can actually harm people. In our media world of soundbytes, tweets and headlines; not everyone reads the entire story. In fact, many patients who need medicines get scared and stop taking them. My reason for posting the initial Men's Health article was because a patient whose horribly controlled asthma had been substantially improved with Advair was in my office sick again because she had stopped taking it. Her reason: her fiancee read the Men's Health article and told her her medicine was dangerous.

Medicine and health is complicated. There are some conditions where medication is overprescirbed (antibiotics for colds) and many chronic conditions like high blood pressure and diabetes which remain out of control and probably need even more medications. In addition, there are certainly a host of drugs proven not to be safe (Vioxx), including certain cholesterol medications (Baychol) which were pulled from the market. However, here is the truth about cholesterol lowering medications:

• Currently available cholesterol lowering medications (statins) are the most commonly prescribed medications in the US
• Statins are extremely safe. The main side effect is muscle pains which happen in about 3% of patients, are usually mild, and usually go away.
• Serious side effects from statins do exist, but happen to fewer than one in a million patients, which is safer then most medications we have.
• Statins are likely responsible for the dramatic reductions seen in heart attack and stroke in the US.
• Cardiovascular disease (heart attack, stroke) is the single leading cause of death in the US. It beats cancer, diabetes, and accidents...combined!
• There are more studies on statins then any other medications
• The evidence that statins prevent heart attack and stroke in patients with risk factors is overwhelming.
• There is even talk of a polypill that contains multiple medications including a statin, that everyone over 50 would take to prevent heart attacks and strokes.

Bottom Line: We certainly need more tools and techniques to better identify those at risk and individualize treatment. However, currently LDL cholesterol is one of the best markers we have for cardiovascular disease (our country's leading killer) and we have safe and effective medications proven to lower this risk. Do not be afraid of statins.

Shame on MSNBC (again) for re-purposing inflammatory and potentially dangerous information.

Crestor approved for primary prevention

Today the FDA announced that Crestor (rosuvastatin) is now indicated for primary prevention of cardiovascular disease. I blogged about this a few weeks ago in my post Crestor: Get Ready to Ask Your Doctor for the CRP Test. Which reviewed the advisory board's recommendation to give Crestor this extra indication. Today the FDA made it official.

Specifically, Crestor is now indicated for

" the primary prevention of cardiovascular disease to reduce the risk of stroke, heart attack, and the risk of arterial revascularization procedures (including coronary artery bypass graft, or bypass grafting of a peripheral artery or carotid artery, or angioplasty or stent placement) in individuals who have no clinically evident heart disease but are at an increased risk of heart disease due to the combined effect of the following risk factors:

• Age (> 50 years in men; > 60 years in women), and
• An elevated high-sensitivity C-reactive protein level (> 2 mg/L), and
• Presence of at least one additional cardiovascular risk factor (e.g., high blood pressure, low HDL-C, smoking, or a family history of premature heart disease). "

There are several reasons why this is interesting:

1. It won't be long before Astra Zeneca, the makers of Crestor, advertise this new indication to patients on TV ads. They will likely ask patients to ask their doctor for CRP tests. Not everyone agrees with the use of the CRP test. The US Preventative Health Task Force (same folks that said mammograms under 50 may not be a good idea), also said that there was not enough evidence to test for and treat an elevated CRP. The Jupiter study led to Crestor getting this indication was a large, well done randomized trial and strong enough evidence for the FDA. However, some (like the US task force) don't think one study is enough.

2. Lipitor goes generic within a year. Lipitor is the number one selling drug in the country. A generic version of Lipitor could thus save millions. However, Lipitor does not have the indication for primary prevention of heart disease for patients with relatively normal cholesterol. I have previously blogged about what is meant by "an indication." Essentially, this means that the drug companies can only market to patients and doctors what the FDA says that they can do. Any other claims are considered "off-label" even if there is strong evidence that the medication does indeed work. My favorite example was back when Zyrtec (Pfizer) was a prescription drug and their marketing campaign focused on Zyrtec treating both indoor and outdoor allergies. The reality is that all allergens produce symptoms from histamines, and all antihistamines work the same way. However, none of Zyrtec's competitors (Allegra, Claritin) could make this claim since they did not have the indication. Thus, Pfizer made it sound like Zyrtec might be better than the others, when in fact, there wasn't really a difference.

However, Crestor's indication takes a more substantial meaning with generic Lipitor on the way. Lipitor has not been shown to do what Crestor did and probably never will, since Pfizer chose not to spend the money on this kind of study with Lipitor's patent fading. Unlike the Zyrtec/Allegra comparison, there may be a difference. Only the very potent, high dose statins have shown to substantially reduce CRP and potentially reverse cardiovascular disease. It is likely that Lipitor at an 80mg dose would do the same thing as Crestor 20mg, but could also have more side effects. Once Lipitor goes generic, the insurance companies are going to make it virtually impossible for patients to get Crestor. Yet, for primary prevention (as well as other more agressive lipid lowering goals), Crestor may be exactly what patients need.

3. The cholesterol guidelines that most physicians accept are the Adult Treatment Panel (ATP) III from the NIH's National Heart, Lung and Blood Institute. These guidelines are about a decade old. The most recent update was back in 2004 in response to several important studies. The next version should be up for public comment in just a few weeks, and done by the summer. The FDA's decision today should force the committee (though they would've probably done this anyway) to address the CRP question. It should be very interesting as well to see if they limit treating CRP with Crestor, or generalize this to other statins.

Crestor: Get Ready to Ask Your Doctor for the CRP Test.

The Wall Street Journal is reporting that and FDA panel voted 12-4 in favor of expanding its indication for treating elevated CRP levels. The FDA doesn't always follow the panel's advice, but it usually does, and probably will in this instance.

What's this about?

The FDA is reviewing the results of the JUPITER trial. I blogged about the results of the Jupiter trial a year ago. Basically this study looked at over 17,000 patients with relatively normal cholesterol levels, but an elevated CRP, which is a marker of inflammation and has been associated with elevated risk for heart attack and stroke. The study was planned for 4 years, but stopped just short of 2 years because they found a substantial benefit for patients taking Crestor. Crestor reduced the risk of heart related deaths, heart attacks, and other serious cardiac complications by 44%. These results are pretty impressive.

What's the FDA have to do with this?
Why is the FDA weighing in on a year old study for a drug that is already on the market? Because Astra Zeneca, the maker of Crestor, is asking the FDA to give Crestor and indication to use Crestor in patients with normal LDL's but elevated CRP's. Currently, all statin medications are only indicated to treat high cholesterol in order to prevent heart attacks and strokes, not to actually prevent heart attacks and strokes irrespective of cholesterol.
I have previously discussed the meaning of "indication" in a post called "An indication for change." Basically, even though Crestor has been proven to prevent heart attacks in patients with elevated CRP and normal cholesterol, the company can not share this information with doctors or advertise this information with patients until it gets the indication. You may notice that a recent Crestor commercial shows a woman over time who states that while she was building a family/career, atherosclerotic plaques were building up in her arterties. The reason this is a focus of the commercial is because Crestor recently got an indication to prevent the progression of atherosclerosis. Since it is the only statin with this indication, the company likely wants to use this as a competitive edge over other statins. It it gets the CRP indication, it will likely use this in advertising messages to doctors and patients.

What does this mean for me?
Actually, the study results have been out for over a year, so this is not really anything new. However, if the FDA does go forward with the panel's recommendations, you will likely hear more about testing for CRP, and your doctor may even recommend this test.

Should I use a statin to treat an elevated CRP?
The jury is still out. This may change though, as the Adult Treatment Panel IV (ATP4), a NIH sponsored group, will soon make its new cholesterol treatment recommendations. They will have to address the CRP issue. The US Preventative Health Task Force (the same government group that recently told younger women to stop getting mammograms) recently stated that they felt there was insufficient evidence to recommend this. This is true, because though there are numerous studies associating CRP to cardiovascular risk, only the JUPITER study shows that treatment works. That being said, the JUPITER study is a very large, randomized trial with substantial differences between treatment and placebo groups, so it should not be ignored. If you don't want to wait until the APT4 weighs in, I would discuss this with your physician. If you are very worried about heart attacks and strokes (possibly a strong family history), but have a normal cholesterol, treating an elevated CRP might be a reasonable option for you.

What do the nay-sayers say?
There are many that will come out against this, regardless of what the ATP4 decides. In addition to stating that there isn't enough data they will say:

• "The patients in the JUPITER study taking Crestor developed diabetes". This is true, but most of the patients in the study were at risk of developing diabetes. Even though there were statistically a few more patients taking Crestor that developed diabetes, it is very unlikely that this was real, and other markers of diabetes were the same
• "You are taking medications that have side effects." It is true that any medication has side effects. However, one interesting thing that came out of the JUPITER study was that there were really no difference in side effects between the placebo group and Crestor group. Given that the 20mg dose used in the study was a relatively high dose, this is pretty impressive. Groups like Public Citizen warned of the dangers of Crestor, but this drug has proven to be quite safe.
• "The patients in JUPITER did not exactly have normal cholesterol levels, and their risk was high." This is a valid criticism. In order to really prove that treating elevated CRP levels with a statin prevents heart attacks, you would need to find patients with an otherwise low risk for heart disease (i.e. not pre-diabetic) and an ldl cholesterol below 100. However, the patients in JUPITER were very representative of the normal population of patients (60% of the country is overweight or obese and many a pre-diabetic) that would not usually get a statin medication.

Do I have to take Crestor to treat an elevated CRP?

This is actually a very important question. Currently, simivastatin is a generic cholesterol medicine and much cheaper then Crestor. Though simvastatin has not shown it can reduce heart attacks by lowering CRP, many physicians will assume a "class effect" and believe that all statins will do this. The problem is that a dose of 20mg of Crestor was used in the JUPITER study, and no amount of simvastatin will lower CRP or LDL by that much. In most studies that have measured CRP lowering with statins, it is the very potent statins that seem to work. In addition, though all statins have shown prevention of heart attacks and strokes, only the more potent statins (Lipitor and Crestor) at high doses have shown to prevent the progresssion and even shown reversal of plaque build up. This will become an even more important issue when Lipitor goes generic.

Bottom Line:
The FDA will very likely approve Crestor for treating elevated CRP levels, and you will hear about this in the media and in advertisements. Though based on one study, the results are compelling enough to discuss this with your doctor and consider CRP testing.