The reports released in the NEJM on  2 Sept   2008 on the SEAS trial ,  and  the cumulative analysis with the other two  current ezetimibe trials-  IMPROVE-IT and SHARP, and the accompanying editorial  Ezetimibe and Cancer — An Uncertain Association, do  not discuss the issue of  the  possible pathogenesis of increased cancer in the SEAS trial. 


What these papers ignore is the long-known  destabilizing effects   (eg Muldoon 1997) on neuroimmunoendocrinology from   driving LDLC too low,  as we reviewed on line on 30 August 2008 below : In the  recent Hong Kong study (Yang, Chan ea 2008), the cancer and death  rates rose progressively when LDLC levels fell   below a mean of 3.28mmol/L  .

in the 2008 Baltimore statin metaanalysis in people from 60yrs upwards, cancer increased by 6%.


The reports on the  ezetimibe ( IMPROVE-IT and SHARP)  trials now under way do not disclose the  mean baseline and interim LDLC levels during these trials-   but  these trials have run respectively only  a mean of 1 and 2.7years ,  nowhere near the mean duration of 4.3years in the SEAS trial. In the latter, the approximate 50% increase in cancer  (7.5% placebo,  vs 11.16% with ezetimibe)  and 67%  in cancer deaths  (2.5%  on placebo vs 4.1%) associated with +- 50% decrease in mean LDL cholesterol from 3.6 +-1 mmol/L to 1.36mmol/L..


      Overall there was no significant improvement in survival with ezetimibe in the SEAS trial. 


      Wikipedia sums up:  “common adverse drug reactions (≥1% of patients) associated with ezetimibe therapy include: headache and/or diarrhoea. Infrequent  effects (0.1–1% of patients) include: myalgia and/or serious liver damage. Rarely (<0.1% of patients), hypersensitivity reactions (rash, angioedema) or myopathy may occur.[3] …  Clinical trial controversy: In January 2008 ENHANCE- a clinical trial  of Zetia  -showed that the drug  resulted in growth  (not lessening) of  fatty plaques.  Merck and Schering-Plough completed the clinical trial in April 2006 and had initially planned to release the findings no later than March 2007. The companies missed several self-imposed deadlines, and in December 2007, finally agreed to publish the results “soon” after the delays were publicized in news reports. ..   A  March 2008 meeting of the ACC resulted in negative press for drugs like Zetia as Yale University Cardiologist Harlan Krumholz et al  questioned the efficacy of such drugs, that  such pharmaceuticals should not be the first or even second option for prescribing doctors.


        In short, the SEAS and  ENHANCE trials confirm   the probability that such drastic lowering of LDLC has no overall benefit;  but increases the risk of cancer, and statin-related muscle, liver, kidney and lung  damage. If there wa a trend in the SEAS trial to a particular cancer with hypocholesterolemia, it was to prostate, gastric and skin cancer; whereas in the Hong Kong study it was to “cancers of the digestive organs and peritoneum, genitourinary organs, and lymphatic and hematopoietic tissues”

        The Womens’ Health Initiative and therefore the WISDOM  prempro  trials were terminated  in 2002 in people in the same age bracket for far lower increase in cancer.


        Hence, on  strong published evidence,  the  ezetimibe (SHORT and IMPROVE-IT) trials, and the promotion of ever-lower cholesterol bloodlevels, should be stopped now on the basis of no likelihood of gain except in increased cancer and  neuroimmunoendocrine destabilization..


Merck should rather stick to promoting it’s slow release metformin (Glucophage SR) , the only true proven panacea drug ever invented and patented (1922) , as this column points out regularly.


But  major journals and the FDA  and their chief funder Big Pharma do not lightly back off on  a drug registered without longterm evidence of need let alone overall benefit  and safety that has  already grossed some  $5billions…





  1. note from their website that the NEJM will not even accept letter comment on this major issue. Even when the consumers’ health is at stake, it is unwise to upset major advertizers…

  2. From: “Dr. Juliana Chan”
    To: “Neil Burman ”
    Sent: Thursday, September 04, 2008
    Please note that all subjects included in
    our analysis were NEVER exposed to statin. Besides, the V shaped relationship of
    low LDL-C with cancer appeared to be attenuated when we included both statin and
    non-statin users in our analysis. Thus, our paper highlights the complex relationship between LDL-C and cancer risks which cannot be used to explain the findings of the recent SEAS study.

  3. The fur flies over the issue of cancer and statins.

    Rebuttal and counter-rebuttal:
    Dr Uffe Ravnskov author of The Statin Myth points out (JNCI 2008:100:972-4) that there may be serious bias in excluding nonmelanoma skin cancer from studies of cancer after statins; with in addition increased breast cancers and lymphoma in some statin trials.
    Drs Farwell, Scranton ea rebut.

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