[fgummett]

CTV.ca | Cholesterol drug lowers blood clot risk, study says
Updated Sun. Mar. 29 2009 1:35 PM ET
The Associated Press

ORLANDO, Fla. -- Statin drugs, taken by millions of Americans to lower cholesterol and prevent heart disease, also can cut the risk of developing dangerous blood clots that can lodge in the legs or lungs, a major study suggests.

The results provide a new reason for many people with normal cholesterol to consider taking these medicines, sold as Crestor, Lipitor, Zocor and in generic form, doctors say.

In the study, Crestor cut in half the risk of blood clots in people with low cholesterol but high scores on a test for inflammation, which plays a role in many diseases. This same big study last fall showed that Crestor dramatically lowered rates of heart attacks, death and stroke in these people, who are not usually given statins now.

"It might make some people who are on the fence decide to go on statins," although blood-clot prevention is not the drugs' main purpose, said Dr. Mark Hlatky, a Stanford University cardiologist who had no role in the study.

Results were reported Sunday at the American College of Cardiology conference and published online by the New England Journal of Medicine.

The study was led by statistician Robert Glynn and Dr. Paul Ridker of Harvard-affiliated Brigham and Women's Hospital in Boston. Ridker is a co-inventor on a patent of the the test for high-sensitivity C-reactive protein, or CRP. It is a measure of inflammation, which can mean clogged arteries or less serious problems, such as an infection or injury.

It costs about US$80 to have the blood test done. The government does not recommend it be given routinely, but federal officials are reconsidering that.

For the study, researchers in the U.S. and two dozen other countries randomly assigned 17,802 people with high CRP and low levels of LDL, or bad cholesterol (below 130), to take dummy pills or Crestor, a statin made by British-based AstraZeneca PLC.

With an average of two years of followup, 34 of those on Crestor and 60 of the others developed venous thromboembolism -- a blood clot in the leg that can travel to the lungs. Several hundred thousand Americans develop such clots each year, leading to about 100,000 deaths.

However, this is uncommon compared to the larger number who suffer heart attacks. Many doctors have been uncomfortable with expanding statin use to people with normal cholesterol because so many would have to be treated to prevent a single additional case.

"I don't know that it changes the big picture very much" to say that a statin can prevent blood clots, Hlatky said. "Where do you draw the line? Are we giving it to 10-year-old kids that are fat?"

AstraZeneca paid for the study, and Ridker and other authors have consulted for the company and other statin makers. Many doctors believe that other statins would give similar benefits, though Crestor is the strongest such drug. It also has the highest rate of a rare but serious muscle problem, and the consumer group Public Citizen has campaigned against it, saying there are safer alternatives.

Crestor costs $3.45 a day versus less than a dollar for generic drugs. Its sales have been rising even though two statins -- Zocor and Pravachol -- are now available in generic form.

Researchers do not know whether the benefits seen in the study were due to reducing CRP or cholesterol, since Crestor did both. Another new analysis reported Sunday and published in the British journal the Lancet found that the patients who did the best in the study were those who saw both numbers drop.

Many doctors remain reluctant to expand CRP testing or use of statins. A survey by the New England journal found them evenly divided on the questions. Others questioned why so few people in the study were getting other treatments to prevent heart problems.

"If more of them were on aspirin, you would have less benefit from the statin," said Dr. Thomas Pearson of the University of Rochester School of Medicine and Dentistry.

Dr. James Stein of the University of Wisconsin-Madison said that doctors examining treatment guidelines should pay close attention to the new results.

He said the CRP test had helped him convince patients that they need to be on a statin drug.

"There are very few times you can say to a patient, 'this medicine is going to keep you alive.' We should try not to pick apart studies that save lives," Stein said.

And here is the NEJM arcticle: NEJM -- A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism

[foxl]

Gee, now if only I could get it to change the baby, and walk the dog ...

Seriously, I would love to think it helps for that.

[foxl]

Statins can lower blood clot risk, study says - Heart health- msnbc.com

Just read this version (pretty similar). It at least acknowledges controversy ... but I loved the line that "Many doctors remain reluctant to expand CRP testing or use of statins. A survey by the New England journal found them evenly divided on the questions. Others questioned why so few people in the study were getting other treatments to prevent heart problems."

Quick -- go chew out your Dr. for not prescribing this!

[lrhughes]

Linda! I second that!
BTW - you can get all the same benefits by changing your diet and exercising! Doctors put me on statins for a a while just because the ADA says all diabetics ought to be taking them, HOWEVER, the statins almost destroyed my liver! Go figure.

[foxl]

Originally Posted by lrhughes

Linda! I second that!
BTW - you can get all the same benefits by changing your diet and exercising! Doctors put me on statins for a a while just because the ADA says all diabetics ought to be taking them, HOWEVER, the statins almost destroyed my liver! Go figure.

Well considering they are supposed to check your liver enzymes every three months on the darn gosh things ... I would not be surprised. Is your liver better now?

[fgummett]

I tend to agree with the statement:

"If more of them were on aspirin, you would have less benefit from the statin"

but also in regards your quoted...

Others questioned why so few people in the study were getting other treatments to prevent heart problems.

...I note in the NEJM article, that the selection criteria for the Study Population includes the following

a low-density lipoprotein (LDL) cholesterol level of less than 130 mg per deciliter and a high-sensitivity C-reactive protein level of 2.0 mg per liter or more ... and a triglyceride level of less than 500 mg per deciliter

[my bold emphasis]

Yes, less than 500mg/dl can mean in the safest range, say below 70mg/dl but it can just as easily mean in a very high range anything up to 499mg/dl which would indicate the LDL volume was made up of the most dangerous small dense molecules regardless of the volume as discussed in this PDF : The Role of LDL Particle Size Assessment

[foxl]

Originally Posted by fgummett

I tend to agree with the statement:
but also in regards your quoted......I note in the NEJM article, that the selection criteria for the Study Population includes the following [my bold emphasis]

Yes, less than 500mg/dl can mean in the safest range, say below 70mg/dl but it can just as easily mean in a very high range anything up to 499mg/dl which would indicate the LDL volume was made up of the most dangerous small dense molecules regardless of the volume as discussed in this PDF : The Role of LDL Particle Size Assessment

FIVE HUNDRED??? Okay -- I do so totally NOT have the metabolic syndrome.

[fgummett]

Quite... someone who has such a high Trigs should really be on some other intervention already. To me it is remarkable that they seem to suggest that all is well just so long as the LDL volume is low enough

[fgummett]

OK... how the heck do we keep getting fed such poor information from those we are supposed to be able to trust?

In further reviewing the NEJM article I note the following:

randomly assigned 17,802 apparently healthy men and women

During a median follow-up period of 1.9 years (maximum, 5.0), symptomatic venous thromboembolism occurred in 94 participants: 34 in the rosuvastatin group and 60 in the placebo group.

Among the 94 cases of symptomatic pulmonary embolism or deep-vein thrombosis, 44 occurred in patients with cancer or recent trauma, hospitalization, or surgery (i.e., provoked events)

yet somehow this is interpreted to say:

rosuvastatin significantly reduced the occurrence of symptomatic venous thromboembolism

I'll leave you to read for yourself who paid for this study but seriously, does this make sense to anyone?

After following 17,802 participants for up to 5 years, 94 had dangerous blood clots of which 44 followed trauma, surgery, cancer etc... I wonder how many had side-effects from the medication?

I'm not that good at math but can someone please tell me what 94 out of 17,802 is as a percentage?

[REDLAN]

nice critique of the study Frank!

The risk of thromobembolism amongst the study participants works out at 0.53% over 2 years - i.e. very low risk.

A much more useful statistic is NNT (number needed to treat). It works out as follows for unprovoked events

on statins there were 0.08 events per 100 person-years
on the placebo there were 0.16 events per 100 person years.

meaning that statins reduced events by 0.08 per 100 person years. Therefore in 1 year to prevent 1 episode of thromboembolism you would need to treat 1250 people. Not terribly impressive really

There are as always several different kinds of signficance....

statistical significance is not always the same as clinically significant, which is not always the same as personally significant.

Is this study more to do with marketing than it is to do with benefit for patients, I wonder??

[fgummett]

Thanks REDLAN.

I have to say that this kind of thing has me feeling pretty militant now: when I see the huge discrepancy between the headline offered us by the media and then read all the way down to the actual study with a critical eye.

[fgummett]

Originally Posted by REDLAN

Therefore in 1 year to prevent 1 episode of thromboembolism you would need to treat 1250 people.

As above, I have to wonder how many of those 1,250 people may have side-effects from this medication so that 1 of them may have a reduced risk of a dangerous blood clot?

---

BTW Linda, in further reading around this subject I note a concern about the use of Statins + Niacin for example: Important safety information on statins

Before taking a statin, patients should tell their doctor or pharmacist if they:

* are pregnant, intend to become pregnant, are breast-feeding or intend to breast-feed;
* have thyroid problems;
* regularly drink three or more alcoholic drinks daily;
* are taking other cholesterol lowering medication such as fibrates (gemfibrozil, fenofibrate) or niacin;
* are taking other medications, including prescription, non-prescription and natural health products, as drug interactions are possible;
* have a family history of muscular disorders;
* had any past problems with the muscles (pain, tenderness), after using a statin;
* have kidney or liver problems;
* have diabetes;
* have undergone surgery or other tissue injury;
* do excessive physical exercise.

and the Crestor (rosuvastatin calcium) Product Monograph itself states that it is contrainidicated with

Concomitant use of a fibrate or niacin

[lrhughes]

Linda,
Thanks for asking! Yes my liver is much better.

[foxl]

Originally Posted by fgummett

BTW Linda, in further reading around this subject I note a concern about the use of Statins + Niacin for example: Important safety information on statins

and the Crestor (rosuvastatin calcium) Product Monograph itself states that it is contrainidicated with

Well I am on Simvastatin ... but actually there are SEVERAL warnings in that list that should apply to me -- hypothyroid, muscle issues ... and of course my long-lived pal, Niacin. It will be interesting to see my liver enzymes, in June ... I probably WILL be going off the simvastatin then ... I would like to think.

[fgummett]

OK... call me suspicious but I just noticed that the news report I posted yesterday has been updated today with ALL the negative comments removed, and an even more postive spin on the statin... WTF!

CTV.ca | Cholesterol drug lowers blood clot risk, study says

Compare this to the original that I posted at the start of this thread so much for unbiased reporting of the news.

Cholesterol drug lowers blood clot risk, study says

Updated Mon. Mar. 30 2009 12:40 PM ET

CTV.ca News Staff

Statins, medications designed to lower cholesterol and prevent heart disease, can also cut the risk of developing major blood clots, a huge new study suggests.

"It is another benefit of an extraordinary class of drug," said Dr. Paul Ridker of Brigham and Women's Hospital in Boston, who led the study.

The findings come from data from the Jupiter trial, a landmark study of 17,802 patients with healthy cholesterol levels but high levels of a protein associated with heart disease, called C-reactive protein, or CRP.

Jupiter found that the statin Crestor dramatically cut deaths, heart attacks and strokes in those patients -- who are not usually given statins.

Now, a sub-analysis of the data from Jupiter finds that Crestor, known as rosuvastatin, also reduces the risk of venous thromboembolism by 43 per cent in those patients.

Venous thromboembolism (VTE) is a blood clot in a vein. The most common form, called deep vein thrombosis, usually occurs in the deep veins in the legs. If the clot dislodges and travels to the lungs, it can be fatal.

For the study, researchers divided the men and women into two groups: one took 20 milligrams of Crestor once a day; the rest took a placebo.

After an average of two years, 34 of those on Crestor developed VTE compared to 60 in the placebo group.

What's more, there was also no bleeding risk with Crestor, which is an issue with other anti-clotting medicines, such as aspirin.

Researchers do not know whether the benefits were due to reducing CRP or cholesterol, since Crestor did both. But Ridker, who has studied many statin drugs, believes that other statins would offer similar benefits similar.

Various anti-coagulant drugs, such as warfarin, are already given to patients who suffer a blood clot in order to prevent more from developing. This is the first time a statin has been shown to prevent VTE.

The results were reported Sunday at the American College of Cardiology conference and published online by the New England Journal of Medicine.

"The results of this sub-analysis are very interesting, as they appear to show real benefit in terms of reduction of VTE risk in a very large patient population," said Dr. Subodh Verma, a cardiac surgeon at St. Michael's Hospital in Toronto and a Jupiter investigator.

Original version says :

"If more of them were on aspirin, you would have less benefit from the statin," said Dr. Thomas Pearson of the University of Rochester School of Medicine and Dentistry.

New version says :

What's more, there was also no bleeding risk with Crestor, which is an issue with other anti-clotting medicines, such as aspirin.