Statins Don’t Raise Cancer Risk, But Low LDL Might
13 CommentsBy Ed Silverman // August 21st, 2008 // 7:34 am
Those wildly popular statins, which are taken by millions of Americans, don’t raise the risk of cancer, after all, according to a new report in the Journal of the American College of Cardiology. Last year, the same authors from Tufts University School of Medicine published a paper that found cancer rates rose in tandem with lower cholesterol levels in patients taking statins.
The new report, however, shows nearly an identical relationship of more malignancies in people with lower cholesterol, even when they weren’t taking the meds. The findings appear to clear statins from responsibility for the cancers, Richard Karas, director of preventive cardiology at Tufts Medical Center and the senior author of the paper, tells Bloomberg News.
“We found that there is indeed an association, that the lower the LDL cholesterol, the higher the risk of cancer,” Karas tells Heartwire. “Despite the LDL-lowering capacity of statins, however, the data are quite reassuring that statins don’t increase the risk of cancer.”
The study analyzed the findings from 15 statin trials involving nearly 100,000 patients, but because each person’s data wasn’t reviewed, the researchers were unable to pinpoint the reason cancer rates rose as cholesterol fell. Some previous trials found statins raised cancer risk, while others found a decreased rate, Karas adds. When all were taken together in the current study, it becomes clear that on average they have no impact on the risk of cancer, he tells Bloomberg.
Overall, there were 12.7 cancers diagnosed for each 1,000 patients given statins every year, and 12.6 cancers for each 1,000 people in the comparison groups who didn’t get the pills. The drugs lowered LDL by an average of 40 points in the studies, without changing the total cancer risk. As a result, the cancer risk was lower in statin patients than in those not taking the drugs at each cholesterol level.
However, The findings aren’t definitive and don’t prove that getting cholesterol levels down to really low levels is safe when it comes to cancer, Anthony DeMaria, editor-in-chief of the journal, and Ori Ben-Yehuda from the University of California, San Diego Medical Center, wrote in an editorial.
Another study known as SEAS that was released last month found patients getting Vytorin, the most powerful medication to lower cholesterol levels, were more likely to develop cancer than those given a placebo. While an initial review of two more studies that are under way failed to find any risk, those studies were shorter and none of the trials gave LDL levels, DeMaria and Ben-Yehuda wrote.
“While statin treatment in itself appears not to increase the risk of cancer, the issue of a possible link between very low LDL-C levels and cancer has not been fully resolved,” they wrote. “Given the importance of the topic, it is paramount that the Food and Drug Administration and the pharmaceutical industry promptly analyze and report the cancer incidence in the various trials.”
Early, undiagnosed cancers may explain the findings, according to Daniel Steinberg, from the University of California, San Diego. This is known as the “unsuspected sickness phenomenon,” which occurs because cancer can significantly lower cholesterol levels up to 10 years before symptoms appear, he wrote in a second editorial.
“If you measure serum cholesterol levels in a large, randomly chosen population and then simply follow that population for 5 years - without intervention of any kind - there will be more cancer deaths in those who had the lowest cholesterol levels to begin with,” he tells Bloomberg. “Neither statin treatment itself not the low LDL levels induced by statins increases the risk of cancer.”
Statins generated $33.7 billion in sales last year, led by Lipitor, the world’s top-selling drug. They work by blocking an enzyme the body needs to produce cholesterol, thereby lowering cholesterol levels. They’ve been proven to prevent and reduce deaths from heart disease, the leading killer worldwide.
And for those interested in full disclosure and industry ties, this appears at the bottom of the study: “Dr. Alsheikh-Ali is currently a recipient of a faculty development award from Pfizer/Tufts Medical Center. Dr. Kent has received research support from Pfizer. Dr. Karas has received honoraria from Merck and Abbott, and research support from AstraZeneca.”
UPDATE: Karas writes us to say “There was no specific funding obtained for this study. These analyses were done on a database we built from published data.”
Condor
As ever, excellent coverage, here, Ed!
Your very comprehensive, and balanced, take led me to weave several prior threads releated to this complex elevated cancer incidence rate tapestry together — including Dr. Roy Poses’ (on high-handed dismissals of causation), and PM’s (over at Gooznews — on a possible “mechanism of action”), to explain the data you summarize, and the journal reports.
Do take a look:
http://shearlingsplowed.blogspot.com/2008/08/pharmalot-new-insights-on-low-ldl-and.html
Cheers!
vince
Statins lower LDL low LDL appears to increase the risk of cancer so while taking statins increases your chance of cancer it really was not the statin it was the lower LDL level . Who funded this study . These fellows seemed to work hard to clear this connection
Justice in Michigan
I am a bit confused by these sentences:
“The drugs lowered LDL by an average of 40 points in the studies, without changing the total cancer risk. As a result, the cancer risk was lower in statin patients than in those not taking the drugs at each cholesterol level.”
Can someone clarify now B follows A? Thanks!
Piper
They used meta-regression to line up the placebo arm with the statin, which showed that at the cross-section of the arm, the cancer rates were the same. As a result, the investigators concluded that at lower LDL levels, the placebo arm would have shown higher cancer rates. In reality, the statin arm showed an excess of 2.2 cancers per 1,000 person-year for every 10 mg/dl decrease in LDL [95% confidence interval: 0.7 to 3.6, p=0.006], vs. the control arm, which showed 1.2 cancers for every 10 mg/dl decrease in LDL [95% confidence interval: -0.2 to 2.7, p=0.9].
Insider
http://pharmagossip.blogspot.com/2008/08/fred-hassan-spots-opportunity.html
Enjoy!
Justice in Michigan
Thanks, Piper, but I still need some translation for my non-statistical mind.
Would the following be true, based on this study:
Lower levels of LDL are associated with higher rates of cancer.
That is true whether those levels, whatever they are, are in pts who are not on statin therapy or those who are.
Or am I still not getting it? For example, do pts whose LDL is pushed down to, say, 50 via statins have the same cancer rate as those who have 50 “naturally”?
If that cancer rate is higher than those who have an LDL of, say, 100, is it not _possible_ (though not shown) that attaining such levels via statins _does_ correlate with cancer risk?
Obviously, the core question here concerns unintended/unknown consequences of aggressive statin tx. Does this study raise that question or not? I’m still unclear.
Vince
“The drugs lowered LDL by an average of 40 points in the studies, without changing the total cancer risk. As a result, the cancer risk was lower in statin patients than in those not taking the drugs at each cholesterol level.”
This sentence is confusing almost by design. Lets see if we can make sense of it. Low LDL is associated with increased cancer risk take low LDL give time wally cancer. When you take an LDL level say 75 without statins those on statins with that same level have less cancer than those with the same level naturally. Why. Time. Given time those who have reduced LDL with statins will probably have more cancer than those at the same start level who chose not to reduce LDL level.
LILLI
We will never the the truth about Statins or al lmedications. But I do know even if they may hel[p some people, Maybe? Statins are causing many horrors and death. I speak from a tragic experienc. Elected and Appointed officals must stop protecting the evils of the pharmaceuticals, medication is not supposed to make executives, investors, federal and state elected officials financial wealthy.
Justice in Michigan
Yikes. I still feel like I’m in Wonderland.
Does “Wally” = Voila?
Anyway, I think I get the drift. At _this point_ statin induced low LDL, compared with Mother Nature induced low LDL, the statin folks have shown less cancer.
But, as for the future, only the Shadow knows…
C’est ca?
Ed - you wrote it. Can you help this poor soul?
Justice in Michigan
OK. Having just talked with the Mad Hatter and reread the piece, here is what I gather…
We don’t know. Statins are _not_ “off the hook” to the extent that the correlation with cancer and low LDL is real and statins yield low LDL. The initial association may be an artificact of other physio processes. Or it may not be.
Bottom line. There are a lot of people who have a lot invested (literally) in the NCEP guidelines. I do not anticipate that “vigorous scentific debate” - as we have seen it in action - will make it easy to sort things out.
MD 1
It appears that ezetimibe may be the culprit!
Doug Bremner
I think the key point is made by Piper, that the statin arm showed an excess of 2.2 cancers per 1,000 person-year for every 10 mg/dl decrease in LDL [95% confidence interval: 0.7 to 3.6, p=0.006], vs. the control arm, which showed 1.2 cancers for every 10 mg/dl decrease in LDL [95% confidence interval: -0.2 to 2.7, p=0.9].
In other words, this analysis confirmed the earlier paper by the same group (which didn’t get any press) that aggressive lipid lowering with statins is associated with an increase in cancer. But now we have a grant from the manufacturer, so the conclusions are changed.
Piper
Doug has it. The control group is unlikely to achieve a -40 mg/dl change in LDL (no matter how much oatmeal they eat), whereas the statin groups can do so in a few weeks time. Maybe lowering LDL to the level of babies (50 mg/dl) increases cancer risk, maybe not. The real point is, it’s not going to get there on its own….unless the person already has cancer (a reason for very low LDL levels in people with previously normal levels).