Study review: cerivastatin

I'd like to start an occasional series of blog posts on The Heart Scan Blog in which I review studies relevant to the whole heart scan score reversal experience.

In a previous post, Don't be satisfied with "deceleration,"I discussed the BELLES Trial (Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES)), in which either atorvastatin (Lipitor), 80 mg, or pravastatin (Pravachol),40 mg, was given to 615 women. Both groups showed an average of 15% annual plaque growth, regardless of which agent was taken and regardless of the amount of LDL cholesterol reduction.

I cited another study in which 471 participants received either Lipitor, 80 mg, or Lipitor, 10 mg. The rate of annual score increase was 25-27%, regardless of drug dose or LDL lowering.

Here's yet another study, a small German experience in 66 patients, with a curious design and using the now-defunct statin drug, cerivastatin (Bayccol, pulled in 2001, nearly simultaneous with the publication of this study, due to greater risk of muscle damage, particularly when used in combination with gemfibrozil). Achenbach et al in Influence of lipid-lowering therapy on the progression of coronary artery calcification: A prospective evaluation reported on this trial in which all participants underwent heart scanning to obtain a heart scan score; no treatment was initiated based on the score. A second scan was obtained after the no treatment period, followed by treatment with cerivastatin, 0.3 mg per day. A third scan was finally obtained.

In year one without treatment, the average increase in heart scan scores was 25%. In year two with cerivastatin, the average increase in heart scan score was 8.8%. In 32 participants who achieved LDL<100 mg/dl on the drug, there was an average modest reduction in heart scan scores of 3.7% (i.e., -3.7%).

Now, that was eye-opening. Why did this small study achieve such startlingly different results from the other two studies that showed relentless progression despite even high doses of Lipitor? That remains unanswered. Was cerivastatin unique among statins? Did the unique two-phase trial design somehow change the outcome by triggering participants to change lifestyle habits after their first scan (since most exhibited an increase in score; they were not "blinded" to their scores). Those questions will remain unanswered, since the drug has been made unavailable. This smal l study had actually been intended to be larger, but was prematurely terminated because of cerivastatin's withdrawal.

This experience is unique, as you can see, compared to the two other studies. But it was also smaller. The results are also different than what I have seen in day-to-day practice when I've seen people treated with statin drugs alone (not cerivastatin, of course): rarely do heart scan scores stop increasing. While slowing does usually occur (18-24% per year rates of annual score increase are very common in people who do nothing but take a statin drug and make modest lifestyle changes), I have personally seen only two people stop their score with this strategy alone. Nobody has ever dropped their score taking a statin alone, in my experience.

You can also see the nature of clinical studies: single or limited interventions instituted in order to control for unexpected or complex effects. If three different treatments are used, then what desirable or undesirable effects, or lack of an effect, is due to which treatment agent?

My experience is that no single treatment stops or reduces heart scan scores. It requires a more rational effort that includes 1) identification of all causes of coronary plaque (e.g., low HDL, high triglycerides, Lp(a), small LDL, deficiency of vitamin D, etc, none of which are substantially affected by statin drugs), and 2) correction of all causes. That simple concept has served us well.

Comments (10) -

  • G

    11/27/2007 3:21:00 AM |

    Baychol ('gorilla'-statin when it came out) had a halogenated side group, which means biologically, this gave it 'super' powers.  Other drugs with halogens are also stronger as well (ie topical steroid Clobetasol). Unfortunately, Baychol also had 'super' strong side effects as well! including death from rhabodmyolysis (breakdown of muscle fibers which then leads to 'clogging up' the kidneys when the myoglobins are released into the blood stream, leading to multiple organ failure). Car accident, trauma and marathon runners can get the condition as well.
    I like your scientific method of accurately assessing various dysfunctions of the lipoprotein patterns and correcting with modifications in various strategies (D3, B3, monounsaturated nut oils, etc). Tying this in with tracking the size of shrinking calcium deposits in plaque make a lot of sense (and of course backed up with data, like the one you just posted!)...

    BTW, with erectile dysfunction associated with atherosclerosis, do you also see symptom reversal with the TYP plan? at what level of CAC reversal?  Do you see less use of Viagra later?
    Do you have a cure for white hair too (* ha ha haaaa *)? Global warming?  Amazon de-forestation? You're so humble!
    THANK YOU! G

  • Dr. Davis

    11/27/2007 12:12:00 PM |

    Hi, G--

    As always, thanks for the insights.

    Because 99% of the people who participate in the program begin with asymptomatic coronary plaque, it's not possible to say if symptoms are relieved. The occasional person who chooses this program but has anginal chest pain has indeed experienced complete elimination of symptoms.

    Re: erectile dysfunction. Also, no systematic tracking, so I don't know. Also, I have to admit not purposefully looking for it in men well into the program. But a great thought! It would indeed make sense that restoration of endothelial function and erectile capacity would accompany plaque control and/regression.

  • Anonymous

    11/27/2007 6:00:00 PM |

    Geez Doc, I wish you would have put the last paragraph first on your Blog. I was just about to throw up my hands in despair and call in for a double cheese all meat pizza on wheat, thinking all was lost. I was greatly releived to see I might still make it a while with low dose(10mg)lipitor, 1500 Niacin, Aspirin, and 2000IU D3. With exercise & diet I have worked hard to get LDL,Trigs,LP(a) all in the 30,s. With HDL at 68 I now see hope...don't do that again please!  Over&Out

  • Dr. Davis

    11/27/2007 10:39:00 PM |

    Well, my motivation for posting these occasional summaries of prior clinical studies is to provide, bit by bit, some of the rationale behind the Track Your Plaque program and to show why the simple-minded "take your statin and shut up" approach simply doesn't work.

  • G

    11/28/2007 11:19:00 PM |

    Theoretically, ED and peripheral vascular disease should regress ('cured' perhaps?) if sufficient plaque reversal occurred and original blood flow were restored... wouldn't you think?  ED is frequently common in T2DM and pre-CAD (I made that up) individuals.

    I customarily ask about ED because I use it as a motivating 'factor' in my strategy to get individuals to comply with changes to improve T2DM (yes, I just gave all my secrets now!).  You'd be surprised how effective this strategy is (of course only men -- I use a diff one for females)! Often people will not make necessary changes for 'health' reasons as you know.  The justifications are typically everything-but!  

    You know, I can tell that you're not in the business of selling books, eh?  You're strength is as an innovator imparting knowledge/power...saving lives... preventing unnecessary tragedies...  (THANK YOU FOR ALL YOU DO!)  if you notice improvement in ED, I'd suggest you change your book title to... you know to reach greater target audiences! (well, you'll get the men then you'll have to trust they'll share with their partners)
    'TYP -- Reverses ED and Heart Disease'
    'Don't Live with ED or Coronary Heart Disease'
    'Erectile Dysfunction can be erased, just like your CAD'
    'Better in bed, greater longevity'

    *ha haa haaa* i'm j/k... who is your marketing person?!! not very sexy or splashy... (pardon, if it is you!)

  • bobb

    11/30/2007 6:05:00 AM |

    Dr Davis,

    Two years ago my calcium score was 145.  I am 58 and my score is 294!
    I am very fit, work out 4 times a week with weights and cardio and have for years.  I take 80 mg of vitorin, fish oil, folic acid, nacin, and 2 baby asprin a day. My cholesterol is 142, Hdl 79, LDL 54 and triglycerides 47!  I am 5 9 and 165 lb.  

    Given this I can not seem to stop the increases in calcium.  What else can I do.

    Bill Blanchet is my Doctor!

    Thanks!!

  • Dr. Davis

    11/30/2007 12:38:00 PM |

    Bobb--

    Clearly you can get no more benefit out of squeezing more out of  cholesterol values. I would propose that you and Dr. Blanchet (a refreshingly open-minded physician who I'm going to invite to become a panel member on Track Your Plaque) consider several issues:

    1) Have all causes beyond cholesterol (HDL, LDL, etc.) been identified?

    2) Have you addressed vitamin D? Vitamin D is a huge effect.

    I would invite you to look at our website, www.trackyourplaque.com, for much more information. There is no 10 cent answer to your question. A comprehensive approach that corrects all causes is usually necessary.

  • Neelesh

    12/8/2007 4:30:00 AM |

    I accidentally bumped in to this study about the connection between vitamin D3 and ApoA-I, observing that ApoA-I levels are reduced by Vitamin D3.

    http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=16236546

    As far as I know, ApoA-I is a good lipoprotein.

    I tried to find some more material on this topic, but to no avail.

    Is this something that you have seen, Dr Davis?

    Thanks!
    -Neelesh
    http://www.recoverytrail.com/blog/

  • Dr. Davis

    12/8/2007 2:00:00 PM |

    Hi, Neeleesh--

    I don't know what to make of this study. It is clearly counter to what I am seeing in real live humans.

    I see the total HDL and the large HDL subclass (richer in ApoA1) increase, often substantially. So I see the exact opposite.

    My observations on this phenomena are informal. Formalizing this observation is part of a future research project.

  • buy jeans

    11/2/2010 8:22:46 PM |

    Those questions will remain unanswered, since the drug has been made unavailable. This smal l study had actually been intended to be larger, but was prematurely terminated because of cerivastatin's withdrawal.

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