Statin numbers for them that likes 'em

Discussion in 'Health and medical' started by Zee, Mar 6, 2004.

  1. Zee

    Zee Guest

    I guess we'll just have to extrapolate what the numbers
    would be now, three more years into use and millions more
    users. What say Chinnis?

    Table 1. Cases of Statin-Associated Rhabdomyolysis by Drug
    (October 1997 through December 2000

    Drug| Number of Cases| Percent of Total Cases| Cases without
    Fibrates| Percent of cases without Fibrates Atorvastatin|
    86| 11.1%| 73| 84.9%

    Cerivastatin| 387| 50.1%| 187| 48.3%

    Fluvastatin| 10| 1.3%| 8| 80.0%

    Lovastatin| 32| 4.1%| 30| 93.8%

    Pravastatin| 70| 9.1%| 62| 88.6%

    Simvastatin| 187| 24.2%| 164| 87.7%

    TOTAL| 772 524| 67.9%|
    =============================
    Table 2. Deaths reported in Statin-Associated Rhabdomyolysis
    (October 1997 through December 2000)

    Drug| Number of Cases(Deaths)| Percent of Total Deaths|
    Cases without Fibrates| Percent of cases of each drug
    without Fibrates

    Atorvastatin| 13| 18.1%| 11| 84.6%

    Cerivastatin| 20| 27.8%| 10| 50.0%

    Fluvastatin| 1| 1.4%| 1| 100%

    Lovastatin| 5| 6.9%| 5| 100%

    Pravastatin| 9| 12.5%| 8| 88.9%

    Simvastatin| 24| 33.3%| 19| 79.2%

    TOTAL| 72*| 54**| 75.0%

    *- 2 deaths were reported where there was use of 2 statins
    concurrently (1 with cerivastatin and simvastatin, 1 with
    pravastatin and simvastatin)

    ** - 1 death with use of 2 statins (pravastatin and
    simvastatin)
    ========================
     
    Tags:


  2. listener

    listener Guest

    On 6 Mar 2004 21:11:59 -0800, [email protected] (Zee) wrote:

    >I guess we'll just have to extrapolate what the numbers
    >would be now, three more years into use and millions more
    >users. What say Chinnis?
    >
    >
    >Table 1. Cases of Statin-Associated Rhabdomyolysis by Drug
    >(October 1997 through December 2000
    >
    >Drug| Number of Cases| Percent of Total Cases| Cases
    >without Fibrates| Percent of cases without Fibrates
    >Atorvastatin| 86| 11.1%| 73| 84.9%
    >
    >Cerivastatin| 387| 50.1%| 187| 48.3%
    >
    >Fluvastatin| 10| 1.3%| 8| 80.0%
    >
    >Lovastatin| 32| 4.1%| 30| 93.8%
    >
    >Pravastatin| 70| 9.1%| 62| 88.6%
    >
    >Simvastatin| 187| 24.2%| 164| 87.7%
    >
    >TOTAL| 772 524| 67.9%|
    >=============================
    >Table 2. Deaths reported in Statin-Associated
    >Rhabdomyolysis (October 1997 through December 2000)
    >
    >Drug| Number of Cases(Deaths)| Percent of Total Deaths|
    >Cases without Fibrates| Percent of cases of each drug
    >without Fibrates
    >
    >Atorvastatin| 13| 18.1%| 11| 84.6%
    >
    >Cerivastatin| 20| 27.8%| 10| 50.0%
    >
    >Fluvastatin| 1| 1.4%| 1| 100%
    >
    >Lovastatin| 5| 6.9%| 5| 100%
    >
    >Pravastatin| 9| 12.5%| 8| 88.9%
    >
    >Simvastatin| 24| 33.3%| 19| 79.2%
    >
    >TOTAL| 72*| 54**| 75.0%
    >
    >
    >*- 2 deaths were reported where there was use of 2 statins
    >concurrently (1 with cerivastatin and simvastatin, 1 with
    >pravastatin and simvastatin)
    >
    >** - 1 death with use of 2 statins (pravastatin and
    >simvastatin)
    >========================

    72 deaths out of hundreds of millions of statin users, even
    then. A tragedy to be sure, but statistically speaking.....?

    Also, it's not made clear if there were underlying issues
    that precipitated a negative interaction.

    Jim, you've been paged.

    L.
     
  3. Anonymous

    Anonymous Guest

    "Zee" <[email protected]> wrote in message
    news:[email protected]...
    > I guess we'll just have to extrapolate what the numbers
    > would be now, three more years into use and millions more
    > users. What say Chinnis?
    >
    >
    > Table 1. Cases of Statin-Associated Rhabdomyolysis by Drug
    > (October 1997 through December 2000
    >
    > Drug| Number of Cases| Percent of Total Cases| Cases
    > without Fibrates| Percent of cases without Fibrates
    > Atorvastatin| 86| 11.1%| 73| 84.9%
    >
    > Cerivastatin| 387| 50.1%| 187| 48.3%
    >
    > Fluvastatin| 10| 1.3%| 8| 80.0%
    >
    > Lovastatin| 32| 4.1%| 30| 93.8%
    >
    > Pravastatin| 70| 9.1%| 62| 88.6%
    >
    > Simvastatin| 187| 24.2%| 164| 87.7%
    >
    > TOTAL| 772 524| 67.9%|
    > =============================
    > Table 2. Deaths reported in Statin-Associated
    > Rhabdomyolysis (October 1997 through December 2000)
    >
    > Drug| Number of Cases(Deaths)| Percent of Total Deaths|
    > Cases without Fibrates| Percent of cases of each drug
    > without Fibrates
    >
    > Atorvastatin| 13| 18.1%| 11| 84.6%
    >
    > Cerivastatin| 20| 27.8%| 10| 50.0%
    >
    > Fluvastatin| 1| 1.4%| 1| 100%
    >
    > Lovastatin| 5| 6.9%| 5| 100%
    >
    > Pravastatin| 9| 12.5%| 8| 88.9%
    >
    > Simvastatin| 24| 33.3%| 19| 79.2%
    >
    > TOTAL| 72*| 54**| 75.0%
    >
    >
    > *- 2 deaths were reported where there was use of 2 statins
    > concurrently (1 with cerivastatin and simvastatin, 1 with
    > pravastatin and simvastatin)
    >
    > ** - 1 death with use of 2 statins (pravastatin and
    > simvastatin)
    > ========================

    Source? Also it is not clear what these numbers mean. But I
    think it means that, e.g., 11.1% of the total cases reported
    were taking Atorvastatin - not that 11.1% of the people
    taking Atorvastatin were afflicted. Right? What was the
    underlying population and how many of them were there? What
    does the total 772 524 mean?

    Thanks.

    Bill
     
  4. Your numbers are absolutely insignificant out of a
    population totaling tens of millions (perhaps hundreds of
    millions) of users. Following the logic represented by your
    posting this information, we should stop driving our cars
    because of the many people killed in auto accidents. I don't
    think so......


    "Zee" <[email protected]> wrote in message
    news:[email protected]...
    > I guess we'll just have to extrapolate what the numbers
    > would be now, three more years into use and millions more
    > users. What say Chinnis?
    >
    >
    > Table 1. Cases of Statin-Associated Rhabdomyolysis by Drug
    > (October 1997 through December 2000
    >
    > Drug| Number of Cases| Percent of Total Cases| Cases
    > without Fibrates| Percent of cases without Fibrates
    > Atorvastatin| 86| 11.1%| 73| 84.9%
    >
    > Cerivastatin| 387| 50.1%| 187| 48.3%
    >
    > Fluvastatin| 10| 1.3%| 8| 80.0%
    >
    > Lovastatin| 32| 4.1%| 30| 93.8%
    >
    > Pravastatin| 70| 9.1%| 62| 88.6%
    >
    > Simvastatin| 187| 24.2%| 164| 87.7%
    >
    > TOTAL| 772 524| 67.9%|
    > =============================
    > Table 2. Deaths reported in Statin-Associated
    > Rhabdomyolysis (October 1997 through December 2000)
    >
    > Drug| Number of Cases(Deaths)| Percent of Total Deaths|
    > Cases without Fibrates| Percent of cases of each drug
    > without Fibrates
    >
    > Atorvastatin| 13| 18.1%| 11| 84.6%
    >
    > Cerivastatin| 20| 27.8%| 10| 50.0%
    >
    > Fluvastatin| 1| 1.4%| 1| 100%
    >
    > Lovastatin| 5| 6.9%| 5| 100%
    >
    > Pravastatin| 9| 12.5%| 8| 88.9%
    >
    > Simvastatin| 24| 33.3%| 19| 79.2%
    >
    > TOTAL| 72*| 54**| 75.0%
    >
    >
    > *- 2 deaths were reported where there was use of 2 statins
    > concurrently (1 with cerivastatin and simvastatin, 1 with
    > pravastatin and simvastatin)
    >
    > ** - 1 death with use of 2 statins (pravastatin and
    > simvastatin)
    > ========================
     
  5. Zee

    Zee Guest

    > "Zee" <[email protected]> wrote in message
    > news:[email protected]...
    > > I guess we'll just have to extrapolate what the numbers
    > > would be now, three more years into use and millions
    > > more users. What say Chinnis?
    > >
    > >
    > > Table 1. Cases of Statin-Associated Rhabdomyolysis by
    > > Drug (October 1997 through December 2000
    > >
    > > Drug| Number of Cases| Percent of Total Cases| Cases
    > > without Fibrates| Percent of cases without Fibrates
    > > Atorvastatin| 86| 11.1%| 73| 84.9%
    > >
    > > Cerivastatin| 387| 50.1%| 187| 48.3%
    > >
    > > Fluvastatin| 10| 1.3%| 8| 80.0%
    > >
    > > Lovastatin| 32| 4.1%| 30| 93.8%
    > >
    > > Pravastatin| 70| 9.1%| 62| 88.6%
    > >
    > > Simvastatin| 187| 24.2%| 164| 87.7%
    > >
    > > TOTAL| 772 524| 67.9%|
    > > =============================
    > > Table 2. Deaths reported in Statin-Associated
    > > Rhabdomyolysis (October 1997 through December 2000)
    > >
    > > Drug| Number of Cases(Deaths)| Percent of Total Deaths|
    > > Cases without Fibrates| Percent of cases of each drug
    > > without Fibrates
    > >
    > > Atorvastatin| 13| 18.1%| 11| 84.6%
    > >
    > > Cerivastatin| 20| 27.8%| 10| 50.0%
    > >
    > > Fluvastatin| 1| 1.4%| 1| 100%
    > >
    > > Lovastatin| 5| 6.9%| 5| 100%
    > >
    > > Pravastatin| 9| 12.5%| 8| 88.9%
    > >
    > > Simvastatin| 24| 33.3%| 19| 79.2%
    > >
    > > TOTAL| 72*| 54**| 75.0%
    > >
    > >
    > > *- 2 deaths were reported where there was use of 2
    > > statins concurrently (1 with cerivastatin and
    > > simvastatin, 1 with pravastatin and simvastatin)
    > >
    > > ** - 1 death with use of 2 statins (pravastatin and
    > > simvastatin)
    > > ========================
    >
    > Source? Also it is not clear what these numbers mean. But
    > I think it means that, e.g., 11.1% of the total cases
    > reported were taking Atorvastatin - not that 11.1% of the
    > people taking Atorvastatin were afflicted. Right? What was
    > the underlying population and how many of them were there?
    > What does the total 772 524 mean?
    >
    > Thanks.
    >
    > Bill

    I think it originates with this, but that's not where I got
    it. http://www4nl.dr-rath-
    foundation.org/DE_STICHTING/Nieuws/2001/2001-08-20.htm

    Here's another. With both, it is *reported* rhabdomyolysis,
    *reported* adverse events. Reported adverse events are
    estimated to be ONE to Ten percent of all adverse events,
    and Terence Young, father of the young woman killed by
    cisapride estimates the number at 25 per cent. Also to
    consider, this is only to the FDA. Does that include Canada,
    Europe, Britain and Australia, for example? I can tell you
    categorically that my illness, disability and several types
    of side effects including spiked CK were NOT every reported.
    Not by my G.P, not by my endocrinologists, either of them,
    both of whom are principals in studies funded by pharma.

    :www.theannals.com/cgi/reprint/36/2/288.pdf+Cases+of+Statin-
    Associated+Rhabdomyolysis+by+Drug&hl=en&ie=UTF-8

    I would also suggest everyone who goes on statins thinks
    they have to take them. We are all under the impression *we*
    have serious need to take this drug. Others may be able to
    get away without it, but not us. We are faced with our
    mortality, impressed by it in fact. I can tell you virtually
    every person I have talked to who has been put on statins
    says some variation of, but really not too varied "oh but I
    have to take them. I have very serious (fill in the blank).

    And there is still no concensus that high cholesterol is
    the problem or that lowerering cholesterol will protect you
    from anything.

    Case in point: a friend who recently had a heart attack and
    had a stent implanted had one blockage, was reassured his
    other arteries are "clean as a whistle". His total
    cholesterol is 6.1. He is on a statin to lower his
    cholesterol. Why?

    B'adant
     
  6. Zee

    Zee Guest

    [email protected] (Zee) wrote in message news:<[email protected]>...

    > I guess we'll just have to extrapolate what the numbers
    > would be now, three more years into use and millions more
    > users. What say Chinnis?
    >
    >
    > Table 1. Cases of Statin-Associated Rhabdomyolysis by Drug
    > (October 1997 through December 2000

    It originates here: http://www.publiccitizen.org/publicatio-
    ns/release.cfm?ID=7051

    And here for an overview of ADRs but not to date:2/288.pdf+fda+adverse+event+reports+on+statins&hl=en&ie=UTF-
    8

    And here for ADRs in under one year for Crestor in Canada
    alone. Type in Crestor, and limit 2003-2003.

    http://www.cbc.ca/news/adr/database/

    Click on the numbers to the left to see what the actual side
    effects experienced were.

    Try your statin here, and keep in mind it is estimated no
    more than 10 percent of serious ADRs are ever reported.

    B'adant
     
  7. listener

    listener Guest

    On 7 Mar 2004 13:05:43 -0800, [email protected] (Zee) wrote:
    >
    >And here for an overview of ADRs but not to date:/288.pdf+fda+adverse+event+reports+on+statins&hl=en&ie=UTF-
    >8

    Again, "....871 reports of statin-associated rhabdomyolysis
    in the 29-month time frame examined, representing 601 cases"
    out of *millions* of statin users is statistically extremely
    small. Isn't it?

    And MOST IMPORTANTLY as the study says:

    "....safety is not an absolute concept, since no drug is
    completely without adverse effects..."

    AND (get a load of this!):

    "In addition, assessing causality was not possible, since
    there was no certainty that a statin or its possible
    interaction with other drugs may have caused the
    rhabdomyolysis because the event may have occurred due to
    some other cause."

    >B'adant

    L.
     
  8. Anonymous

    Anonymous Guest

    "Zee" <[email protected]> wrote in message
    news:[email protected]...
    > [email protected] (Zee) wrote in message
    news:<[email protected]>...
    > Try your statin here, and keep in mind it is estimated no
    > more than 10 percent of serious ADRs are ever reported.
    >
    >
    > B'adant

    I would think that most serious cases would be recognized
    via the CPK test, but maybe not reported - I don't know most
    Drs. habits. But in case of death I would think it would be,
    but again I'm not sure. Also keep in mind that there are
    causes other than statins to Rhabdomyolysis and indeed it
    was known prior to the development of statins.

    Bill
     
  9. listener

    listener Guest

    On 7 Mar 2004 09:56:01 -0800, [email protected] (Zee) wrote:

    >And there is still no concensus that high cholesterol is
    >the problem or that lowerering cholesterol will protect you
    >from anything.
    >
    >Case in point: a friend who recently had a heart attack and
    >had a stent implanted had one blockage, was reassured his
    >other arteries are "clean as a whistle". His total
    >cholesterol is 6.1. He is on a statin to lower his
    >cholesterol. Why?
    >
    >
    >
    >B'adant

    Cholesterol levels are just a piece of the puzzle.
    Studies are beginning to show other factors involved in
    cardiovascular disease. (This actually has been known
    for some time). At the same time, studies are also
    showing *other* benefits from statins besides its
    effective cholesterol lowering abilities. I've been
    posting links to some of them in the past few weeks, in
    case you missed it....:)

    I understand that CAUSers would never want to
    acknowledge that.

    L.

    Here is some useful information for you:

    Simvastatin reduces human atrial myofibroblast
    proliferation independently of cholesterol lowering via
    inhibition of RhoA.

    Porter KE, Turner NA, O'Regan DJ, Balmforth AJ, Ball SG.

    Institute for Cardiovascular Research, Worsley Building,
    University of Leeds, Leeds LS2 9JT, UK.

    Objective: Adverse atrial and ventricular myocardial
    remodeling is characterized by fibrosis, myocyte death or
    hypertrophy and fibroblast proliferation. HMG-CoA reductase
    inhibitors (statins) are widely prescribed cholesterol-
    lowering drugs that also appear to have beneficial effects
    on myocardial remodeling. Although statins are known to
    reduce myocyte hypertrophy, their effect on cardiac
    fibroblast proliferation is unknown. The purpose of this
    study was to investigate the effects of simvastatin on human
    atrial myofibroblast proliferation. Methods: Cardiac
    myofibroblasts were cultured from biopsies of human right
    atrial appendage. Proliferation was quantified by cell
    counting and cell cycle progression determined by
    immunoblotting for Cyclin A. The expression, activation and
    intracellular localization of RhoA were investigated using
    immunoblotting and immunocytochemistry. Results: Simvastatin
    (0.1-1.0 micromol/l) inhibited serum-induced myofibroblast
    proliferation in a concentration-dependent manner at a point
    upstream of Cyclin A expression. These effects were reversed
    by mevalonate or geranylgeranyl pyrophosphate (GGPP), but
    not squalene or farnesyl pyrophosphate (FPP), indicating a
    mechanism involving inhibition of Rho-family GTPases and
    independent of cholesterol synthesis. The effects of
    simvastatin were mimicked by inhibiting Rho
    geranylgeranylation or Rho-kinase activation. Furthermore,
    we demonstrated that simvastatin inhibited RhoA function by
    preventing its association with the plasma membrane and
    hence, its interaction with downstream effectors required
    for cell proliferation. Conclusions: Simvastatin reduced
    proliferation of cultured human atrial myofibroblasts
    independently of cholesterol synthesis via a mechanism
    involving inhibition of RhoA geranylgeranylation. Statins
    may therefore have an important role in preventing adverse
    myocardial remodeling associated with cardiac myofibroblast
    proliferation. PMID: 14985071

    Cholesteryl ester transfer protein concentration is
    associated with progression of atherosclerosis and response
    to pravastatin in men with coronary artery disease
    (REGRESS).

    Klerkx AH, de Grooth GJ, Zwinderman AH, Jukema JW,
    Kuivenhoven JA, Kastelein JJ.

    Department of Vascular Medicine, Academic Medical Center,
    University of Amsterdam, Amsterdam, The Netherlands.
    [email protected]

    BACKGROUND: The TaqIB polymorphism in the cholesteryl ester
    transfer protein (CETP) gene is associated with HDL-C,
    progression of coronary artery disease (CAD) and response to
    pravastatin treatment in men with angiographically proven
    CAD (REGRESS). We hypothesized that differences in CETP
    concentration could explain these associations and now
    investigated whether CETP concentration is an independent
    determinant of these parameters. MATERIALS AND METHODS:
    Plasma CETP concentrations at baseline and after 2 years'
    treatment with pravastatin or placebo were measured (n=674),
    and correlations with lipid and angiographic parameters
    (mean segment- and obstruction-diameter; MSD and MOD), and
    TaqIB genotype were studied. RESULTS: After segregation into
    three groups (baseline CETP<1.58,
    1.58-2.21, >2.21 mg L(-1)), subjects with the highest CETP
    had significantly higher baseline total cholesterol, LDL-C
    and triglycerides (P<0.01), while HDL-C, MSD and MOD were
    not different among these groups. After 2 years of
    placebo, the MSD decreased threefold (P<0.001) and the MOD
    decreased 2.4-fold (P=0.042) more in the highest compared
    with the lowest CETP quartile. Pravastatin treatment
    reduced total cholesterol LDL-C and triglycerides
    significantly more in the highest CETP quartile. Moreover,
    only in the highest CETP quartile, pravastatin
    significantly reduced the MSD- (P=0.003) and MOD-decrease
    (P=0.014) compared with placebo, and, notably, this was
    independent of baseline lipids and differential lipid
    changes in these quartiles. Strikingly, baseline
    associations and treatment responses according to baseline
    CETP were independent of TaqIB genotype. CONCLUSIONS: High
    CETP concentration is associated with faster progression
    of coronary atherosclerosis in men with proven CAD.
    Second, pravastatin yielded the highest improvement of
    lipid and angiographic parameters in patients with high
    baseline CETP independent of baseline lipids, lipid
    changes and TaqIB genotype, indicating that the plasma
    CETP level itself is an important determinant of the
    response to statins. PMID: 14984434

    Does atorvastatin influence serum C-reactive protein levels
    in patients on long-term hemodialysis?

    Vernaglione L, Cristofano C, Muscogiuri P, Chimienti S.

    Nephrology and Dialysis Unit, M. Giannuzzi Hospital,
    Manduria, Italy. [email protected]

    BACKGROUND: The increase in serum C-reactive protein (CRP)
    levels is an independent determinant of cardiovascular
    events in long-term hemodialysis (HD) patients. Recently,
    statins have shown anti-inflammatory properties in addition
    to their lipid-lowering effect. METHODS: We designed a 6-
    month, prospective, randomized, controlled study to assess
    the safety and efficacy of atorvastatin in reducing serum
    CRP levels in long-term HD patients. Patients on HD therapy
    for at least 6 months, with autologous vascular access, were
    included. Patients presenting with illnesses and/or use of
    drugs that may affect CRP levels were excluded. After
    randomization, group A included 16 patients treated with
    atorvastatin (10 mg/d orally), and group B included 17
    patients treated with placebo. Body mass index, Kt/V,
    normalized protein catabolic rate, mean blood pressure, and
    levels of hemoglobin, serum CRP, albumin, creatinine,
    lipids, and enzymes were recorded at baseline and after 6
    months. RESULTS: Qualitative/quantitative parameters were
    homogeneous between the groups at baseline. In group A,
    median serum CRP levels decreased from 9 mg/L (range, 5 to
    22 mg/L) at baseline to 5 mg/L (range, 3 to 16
    mg/L) after 6 months (P = 0.004). In group B, values were 8
    mg/L (range, 4 to 14 mg/L) at baseline and 7 mg/L
    (range, 3 to 17 mg/L) after 6 months (P = 0.98). Serum
    CRP levels were lower in group A than group B at month-
    4 (5 mg/L; range, 3 to 11 mg/L versus 7 mg/L; range, 3
    to 10 mg/L, respectively; P = 0.054) and month-6
    evaluations (5
    mh/L; range, 3 to 16 mg/L versus 7 mg/L; range, 3 to 17
    mg/L, respectively; P = 0.060). After 6 months, only in
    group A was there a significant decrease in serum
    cholesterol levels (P = 0.041) and a significant increase
    in serum albumin levels (P = 0.004). Enzyme levels were
    stable during the study in both groups. CONCLUSION:
    Administration of atorvastatin is safe in patients on long-
    term HD therapy and, in addition to its beneficial
    effects on lipid levels, induces a significant decrease
    in serum CRP levels, with a consequential increase in
    serum albumin levels. PMID: 14981605

    Statin therapy is associated with improved survival in
    ischemic and non-ischemic heart failure.

    Horwich TB, MacLellan WR, Fonarow GC.

    Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, California
    90095-1679, USA.

    OBJECTIVES: This study aimed to investigate the impact of
    hydroxymethylglutaryl coenzyme A reductase inhibitor
    (statin) therapy in patients with advanced heart failure
    (HF). BACKGROUND: Although statins are known to reduce
    mortality in coronary artery disease (CAD), the impact of
    statin therapy in patients with HF has not been well
    studied. Both the potential risks and benefits of statins in
    HF have been described. METHODS: We studied a cohort of 551
    patients with systolic HF (left ventricular ejection
    fraction [EF] <or=40%) referred to a single university
    center for clinical management and/or transplant evaluation.
    Survival without the necessity of urgent heart
    transplantation was determined. RESULTS: The patients' mean
    age was 52 +/- 13 years; mean EF was 25 +/- 7%. Forty-five
    percent of the cohort had CAD, and 45% were receiving statin
    therapy, including 73% and 22% of CAD and non-CAD patients
    with HF, respectively. Patients receiving statins were
    significantly older and more likely to be male, with higher
    rates of hypertension, diabetes, and smoking. The EF and
    cholesterol levels were similar between treated and non-
    treated patients. Statin use was associated with improved
    survival without the necessity of urgent transplantation in
    both non-ischemic and ischemic HF patients (91% vs. 72%, p <
    0.001 and 81% vs. 63%, p < 0.001 at one-year follow-up,
    respectively). After risk adjustment for age, gender, CAD,
    cholesterol, diabetes, medications, hemoglobin, creatinine,
    and New York Heart Association functional class, statin
    therapy remained an independent predictor of improved
    survival (hazard ratio 0.41 95% confidence interval 0.18 to
    0.94). CONCLUSIONS: Statin therapy is associated with
    improved survival in patients with ischemic and non-ischemic
    HF. Randomized trials are needed for confirmation of a
    therapeutic benefit. PMID: 14975476

    Statins prevent bisphosphonate-induced gamma,delta-T-cell
    proliferation and activation in vitro.

    Thompson K, Rogers MJ.

    Bone Research Group, Department of Medicine and
    Therapeutics, Institute of Medical Sciences, University of
    Aberdeen, Foresterhill, Aberdeen, United Kingdom.
    [email protected]

    The acute phase response is the major adverse effect of
    intravenously administered N-BPs. In this study we show that
    N-BPs cause gamma,delta-T-cell activation and proliferation
    in vitro by an indirect mechanism through inhibition of FPP
    synthase, an effect that can be overcome by inhibiting HMG-
    CoA reductase with a statin. These studies clarify the
    probable initial cause of the acute phase response to N-BP
    drugs and suggest a possible way of preventing this
    phenomenon. INTRODUCTION: The acute phase response is the
    major adverse effect of intravenously administered nitrogen-
    containing bisphosphonate drugs (N-BPs), used in the
    treatment of metabolic bone diseases. This effect has
    recently been attributed to their action as non-peptide
    antigens and direct stimulation of gamma,delta-T-cells.
    However, because N-BPs are potent inhibitors of farnesyl
    diphosphate (FPP) synthase, they could cause indirect
    activation of gamma,delta-T-cells owing to the accumulation
    of intermediates upstream of FPP synthase in the mevalonate
    pathway, such as isopentenyl diphosphate/dimethylallyl
    diphosphate, which are known gamma,delta-T-cell agonists.
    MATERIALS AND METHODS: Peripheral blood mononuclear cells
    (PBMCs) were isolated from healthy volunteers and treated
    with N-BP, statin, or intermediates/inhibitors of the
    mevalonate pathway for 7 days in the presence of interleukin
    (IL)-2. Flow cytometric analysis of the T-cell-gated
    population was used to quantify the proportion of gamma,delta-T-
    cells in the CD3+ population. RESULTS AND CONCLUSIONS: The
    ability of N-BPs to stimulate proliferation of CD3+ gamma,delta-T-
    cells in human PBMC cultures matched the ability to inhibit
    FPP synthase. Gamma,delta-T-cell proliferation and
    activation (interferon gamma [IFNgamma] and TNFalpha
    release) was prevented by mevastatin or lovastatin, which
    inhibit HMG-CoA reductase upstream of FPP synthase and
    prevent the synthesis of isopentenyl
    diphosphate/dimethylallyl diphosphate. Desoxolovastatin, an
    analog of lovastatin incapable of inhibiting HMG-CoA
    reductase, did not overcome the stimulatory effect of N-BP.
    Furthermore, statins did not prevent the activation of gamma,delta-T-
    cells by a synthetic gamma,delta-T-cell agonist or by anti-
    CD3 antibody. Together, these observations show that N-BPs
    indirectly stimulate the proliferation and activation of gamma,delta-T-
    cells caused by inhibition of FPP synthase and intracellular
    accumulation of isopentenyl diphosphate/ dimethylallyl
    diphosphate in PBMCs. Because activation of gamma,delta-T-
    cells could be the initiating event in the acute phase
    response to bisphosphonate therapy, co-administration of a
    statin could be an effective approach to prevent this
    adverse effect.

    PMID: 14969398

    Beneficial effects of statins in patients with non-ischemic
    heart failure.

    Laufs U, Wassmann S, Schackmann S, Heeschen C, Bohm M,
    Nickenig G.

    Klinik und Poliklinik Innere Medizin III, Universitat des
    Saarlandes, 66424, Homburg, Germany, [email protected]

    OBJECTIVE: HMG CoA reductase inhibitors (statins) may exert
    a wide array of cholesterolindependent effects including
    antihypertrophic effects on the heart. Their role in the
    treatment of heart failure has not been studied. METHODS AND
    RESULTS: 15 patients with heart failure NYHA II-III based on
    non-ischemic dilated cardiomyopathy were randomized in a double-
    blind study to 0.4 mg cerivastatin or placebo for an average
    treatment period of 20 weeks. Quality of life and exercise
    capacity increased significantly in the statin treatment but
    not in the placebo group (Minnesota Living with Heart
    Failure Questionnaire, 6 min walking test). Concomitantly,
    there was a trend towards increased left ventricular
    ejection fraction (radionuclear ventriculography) and
    improved endothelial function (forearm blood flow). Statins
    decreased plasma concentrations of troponine T, high
    sensitive C-reactive protein (hsCRP), plasminogen activator
    inhibitor-1 (PAI-1) and tumor necrosis factor alpha
    (TNFalpha). CONCLUSIONS: Statins induce benefical effects in
    patients with non-ischemic cardiomyopathy leading to
    improvement of quality of life and exercise capacity
    disclosing a promising novel treatment strategy for patients
    with heart failure. PMID: 14963675

    Statins induce the regression of left ventricular mass in
    patients with angina.

    Nishikawa H, Miura S, Zhang B, Shimomura H, Arai H, Tsuchiya
    Y, Matsuo K, Saku K.

    Department of Cardiology, Fukuoka University School of
    Medicine, Japan.

    Background There is evidence that statins induce the
    regression of cardiac hypertrophy in a transgenic rabbit
    model of hypertrophic cardiomyopathy. Methods and Results
    The association between treatment with statins and the
    regression of cardiac mass (left ventricular mass index,
    LVMI) was investigated in a case - control study using
    transthoracic echocardiography in 304 patients with angina
    who underwent coronary angiography. Those who received
    pravastatin or

    index-matched controls (n=127) were selected. The cases
    showed a significant decrease in LVMI compared with the
    controls. Although the cases included a significantly
    higher percentage of patients with hypertension and
    calcium antagonist (CaA) treatment than the controls,
    there were no relationships between LVMI and either
    hypertension or CaA treatment. Because the cases had a
    significantly higher number of stenosed vessels than the
    controls, LVMI for each number of stenosed vessels was
    analyzed, and a significant interaction effect between the
    association of LVMI with statin and the number of stenosed
    vessels was found. Conclusions Treatment with statins was
    associated with a lower cardiac mass in patients with
    angina, suggesting that this is one of the drugs'
    pleiotropic effects. PMID: 14745145

    Additive benefits of pravastatin and aspirin to decrease
    risks of cardiovascular disease: randomized and
    observational comparisons of secondary prevention trials and
    their meta-analyses.

    Hennekens CH, Sacks FM, Tonkin A, Jukema JW, Byington RP,
    Pitt B, Berry DA, Berry SM, Ford NF, Walker AJ, Natarajan K,
    Sheng-Lin C, Fiedorek FT, Belder R.

    Mount Sinai Medical Center-Miami Heart Institute, Department
    of Medicine & Epidemiology and Public Health, University of
    Miami School of Medicine, Boca Raton, FL 33432, USA.
    [email protected]

    BACKGROUND: In randomized trials of secondary prevention,
    pravastatin sodium and aspirin reduce risks of
    cardiovascular disease. Pravastatin has a predominantly
    delayed antiatherogenic effect, and aspirin has an immediate
    antiplatelet effect, raising the possibility of additive
    clinical benefits. METHODS: In 5 randomized trials of
    secondary prevention with pravastatin (40 mg/d), comprising
    73 900 patient-years of observation, aspirin use was also
    prescribed in varying frequencies, and data were available
    on a large number of confounding variables. We tested
    whether pravastatin and aspirin have additive benefits in
    the 2 large trials (Long-term Intervention With Pravastatin
    in Ischaemic Disease trial and the Cholesterol and Recurrent
    Events trial) that were designed to test clinical benefits.
    We also performed meta-analyses of these 2 trials and 3
    smaller angiographic trials that collected clinical end
    points. In all analyses, multivariate models were used to
    adjust for a large number of cardiovascular disease risk
    factors. RESULTS: Individual trials and all meta-analyses
    demonstrated similar additive benefits of pravastatin and
    aspirin on cardiovascular disease. In meta-analysis, the
    relative risk reductions for fatal or nonfatal myocardial
    infarction were 31% for pravastatin plus aspirin vs aspirin
    alone and 26% for pravastatin plus aspirin vs pravastatin
    alone. For ischemic stroke, the corresponding relative risk
    reductions were 29% and 31%. For the composite end point of
    coronary heart disease death, nonfatal myocardial
    infarction, coronary artery bypass graft, percutaneous
    transluminal coronary angioplasty, or ischemic stroke, the
    relative risk reductions were 24% and 13%. All relative risk
    reductions were statistically significant. CONCLUSION: More
    widespread and appropriate combined use of statins and
    aspirin in secondary prevention of cardiovascular disease
    will avoid large numbers of premature deaths. PMID: 14718320

    Atorvastatin completely inhibits VEGF induced ACE
    upregulation in human endothelial cells.

    Saijonmaa O, Nyman T, Stewen P, Fyhrquist F.

    Minerva Institute for Medical Research, Helsinki, Finland;
    Department of Internal Medicine, Helsinki University Central
    Hospital, Helsinki, Finland.

    Objective: Angiotensin-converting enzyme (ACE) plays an
    important role in the pathophysiology of cardiovascular
    disease. We investigated whether atorvastatin, a powerful
    agent for the prevention and treatment of cardiovascular
    disease influences ACE production in endothelial cells.
    Methods and Results: Human umbilical cord vein endothelial
    cells were treated with VEGF (476pM) which induced ACE
    upregulation. Co-treatment with atorvastatin (0,1-10 micro
    M) dose dependently inhibited VEGF induced ACE upregulation.
    In the presence of mevalonate (100 micro M), atorvastatin
    failed to downregulate VEGF induced ACE production. Co-
    treatment of the cells with either farnesylpyrophosphate
    (FPP, 5 micro M) or geranylgeranylpyrophosphate (GGPP, 5
    micro M) partially inhibited the suppressive effect of
    atorvastatin. Pretreatment of the cells with Rho associated
    protein kinase inhibitor, Y27632 (10 micro M), partially
    inhibited VEGF induced ACE upregulation. VEGF (476pM) caused
    PKC phosphorylation which was inhibited by co-treatment of
    the cells with atorvastatin. Conclusions: Atorvastatin
    inhibited VEGF induced ACE upregulation probably by
    inhibiting PKC phosphorylation. This effect was mediated via
    inhibition of the mevalonate pathway. ACE downregulation may
    be an additional beneficial effect of statins in the
    treatment of cardiovascular disease. PMID: 14704227

    Usefulness of statin drugs in protecting against atrial
    fibrillation in patients with coronary artery disease.

    Young-Xu Y, Jabbour S, Goldberg R, Blatt CM, Graboys T,
    Bilchik B, Ravid S.

    Lown Cardiovascular Research Foundation, Brookline,
    Massachusetts, USA

    Atrial fibrillation (AF) is prevalent in the elderly, in
    patients with hypertension, and in patients with coronary
    artery disease (CAD). We hypothesized that statin therapy
    might be effective in preventing AF in patients with CAD and
    examined this hypothesis in a sample of patients with
    chronic stable CAD without AF, followed prospectively at a
    large outpatient cardiology practice. The association
    between statin use and the risk of developing AF was
    examined univariately and then with adjustment for potential
    confounding factors. Four hundred forty-nine men and women
    between the ages of 40 and 87 years were followed for an
    average of 5 years. Fifty-two patients (12%) developed AF
    during follow-up. Statin therapy was used by 59% of the
    patients during the study period and was associated with a
    significantly reduced risk of developing AF (crude odds
    ratio, 0.48, 95% confidence interval 0.28 to 0.83). This
    association remained significant after adjustment for
    potential confounders, including age, hypertension, left
    ventricular systolic function, occurrence of heart failure
    or acute ischemic events, and baseline cholesterol and
    changes in cholesterol levels (adjusted odds ratio 0.37, 95%
    confidence interval .18 to 0.76). Use of statins in patients
    with chronic stable CAD appears to be protective against AF.
    The underlying mechanism for this effect is unknown but
    appears to be independent of the reduction in serum
    cholesterol levels. PMID: 14675569

    The cardioprotective effects of statins.

    Davignon J.

    Hyperlipidemia and Atherosclerosis Research Group, Clinical
    Research Institute of Montreal (IRCM), 110 Pine Avenue West,
    Montreal, QC H2W 1R7, Canada. [email protected]

    In addition to their lipid-modulating properties, statins
    have a large number of beneficial cardiovascular effects
    that have emerged over time and that were not anticipated
    during drug development. The lipid and nonlipid effects act
    in a concerted way to reduce the ischemic burden of the
    myocardium and to protect it against injury. By acting on
    the vessel wall, statins may prevent lesion initiation and
    repair injuries, enhance myocardial perfusion, slow lesion
    progression, and prevent coronary occlusion. They may also
    directly reduce myocardial damage, favor myocardial repair,
    and protect against immune injury. This review focuses on
    properties of statins that contribute to their
    cardioprotective effect. The first section includes
    information on modulation of vascular tone, endothelial
    permeability and function, inhibition of complement injury,
    curbing of foam cell formation, antioxidant and anti-
    inflammatory properties, and profibrinolytic and
    anticoagulant activities. The second section relates to
    reduction of myocardial necrosis, myocardial hypertrophy,
    blood pressure, and heart failure, as well as mobilization
    of endothelial progenitor cells for repair, angiogenic
    effects, and immunomodulation. In many instances, results of
    in vitro and animal studies have raised expectations and
    prompted studies in humans. Several clinical trials have
    confirmed these expectations and have strengthened the value
    of statins as valuable antiatherosclerotic and
    cardioprotective agents. PMID: 14662105

    Atorvastatin reduces neurological deficit and increases
    synaptogenesis, angiogenesis, and neuronal survival in rats
    subjected to traumatic brain injury.

    Lu D, Goussev A, Chen J, Pannu P, Li Y, Mahmood A, Chopp M.

    Department of Neurosurgery, Henry Ford Health Sciences
    Center, Detroit.

    Statins administered postischemia promote functional
    improvement in rats, independent of their capability to
    lower cholesterol. We therefore tested the effect of statin
    treatment on traumatic brain injury (TBI) in rats.
    Atorvastatin was orally administered (1
    mi/kg/day) to Wistar rats starting 1 day after TBI for 7
    consecutive days. Control animals received saline.
    Modified Neurological Severity Scores and Corner tests
    were utilized to evaluate functional response to
    treatment. Bromodeoxyuridine (BrdU, 100 mg/kg) was also
    intraperitoneally injected daily for 14 consecutive
    days to label the newly generated endothelial cells.
    Rats were sacrificed at day 14 after TBI, and the brain
    samples were processed for immunohistochemical
    staining. Atorvastatin administration after brain
    injury significantly reduced the neurological
    functional deficits, increased neuronal survival and
    synaptogenesis in the boundary zone of the lesion and
    in the CA3 regions of the hippocampus, and induced
    angiogenesis in these regions. The results suggest that
    atorvastatin may provide beneficial effects in
    experimental TBI. PMID: 14987462

    Prevention of atrial fibrillation recurrence by statin
    therapy in patients with lone atrial fibrillation after
    successful cardioversion.

    Siu CW, Lau CP, Tse HF.

    Cardiology Division, Department of Medicine, Queen Mary
    Hospital, The University of Hong Kong, Hong Kong, China.

    The aim of this study was to investigate the effect of
    statin therapy on arrhythmia recurrence in patients with
    lone atrial fibrillation (AF). From July 1998 to December
    1999, 62 patients with lone persistent AF lasting >/=3
    months underwent successful external cardioversion. After a
    mean follow-up of 44 months, 85% had recurrence of AF. The
    use of statins was associated with a significant decrease
    in the risk of arrhythmia recurrence after successful
    cardioversion of AF. The result of this retrospective study
    demonstrates that the use of statins in patients with lone
    AF was associated with a significant decrease in the risk
    of arrhythmia recurrence after successful cardioversion.
    PMID: 14636918

    American Journal of Therapeutics: Volume 10(6)
    November/December 2003

    Statins for Everybody? New Evidence on the Efficacy and
    Safety of the Inhibitors of HMG Co-A Reductase Alcocer,
    Luis* México City General Hospital and National Autonomous
    University of México, México City, Mexico. *Address for
    correspondence: Tuxpan 16, México D.F., 0676, México. E-
    mail: [email protected] Abstract Classically, the
    statins are the first choice drugs when treating
    dyslipidemias, especially in patients with
    hypercholesterolemia alone or accompanied by
    hypertriglyceridemia. The recent evidence of the
    effectiveness, safety and impact comes from hard endpoints,
    as demonstrated in 6 trials which included more than 40,000
    subjects. The statins are being recommended for the
    treatment of a large number of patients with overt coronary
    heart disease, regardless of serum cholesterol levels, in
    patients with acute phases of coronary syndromes, and in
    patients without apparent coronary heart disease with
    moderate risk and average serum cholesterol and LDL
    cholesterol levels. These drugs are also being prescribed to
    patients with high-risk medical conditions that are
    equivalent to coronary heart disease, like diabetes, lower
    limb atherosclerosis, or vascular cerebral disease,
    independent of the basal serum cholesterol levels or LDL
    cholesterol ranging from normal to high. Despite all the
    evidence collected as to the efficacy and safety of these
    drugs, the statins are not sufficiently used in daily
    practice, probably due to the ignorance of new concepts and
    the doubts related to the safety that may be cleared by
    careful analysis of 6 major studies with these drugs.

    Benefits of statin treatment in cardiac syndrome-X1.

    Kayikcioglu M, Payzin S, Yavuzgil O, Kultursay H, Can
    LH, Soydan I.

    Ege University, Medical School, Department of Cardiology,
    Izmir, Turkey. [email protected]

    AIMS: The pathophysiological mechanism in cardiac syndrome-
    X (anginal chest pain, positive exercise test, and
    angiographically normal coronary arteries) has been
    suggested as an impairment in normal endothelial function
    of the coronary microvasculature, resulting in inadequate
    flow reserve. The aim of this study was to determine
    whether statins with proven beneficial effects on
    endothelium, have any effect on endothelial functions and
    exercise induced ischaemia in cardiac syndrome-X. METHODS
    AND RESULTS: Study population consisted of prospectively
    enrolled 40 patients with cardiac syndrome-X. Patients with
    left ventricular hypertrophy, hypertension, diabetes
    mellitus, and LDL levels >/=160 mg/dl were excluded. Half
    of the patients received pravastatin (40 mg/day) for 3
    months irrespective of their lipid values, according to a
    single-blind, randomized, placebo-controlled design.
    Endothelial functions were assessed with high-resolution
    vascular ultrasound, which measured the brachial artery
    flow mediated dilatation (FMD). Lipid measurements, symptom
    limited exercise tests and vascular ultrasound images were
    obtained before and at the end of 3 months. After the
    treatment, FMD improved significantly in pravastatin group.
    Exercise duration, and time to 1mm-ST depression were
    significantly prolonged after statin therapy. Ischaemic
    symptoms and ECG findings during exercise test disappeared
    completely in 5 (26%) patients in the statin group.
    However, there were no significant changes in FMD and
    exercise parameters in placebo group. CONCLUSIONS: Statin
    therapy resulted in beneficial effects on both exercise
    induced ischaemia and FMD in cardiac syndrome-X. The
    mechanism of this beneficial effect is probably the result
    of improvement in endothelial functions. PMID: 14613735

    Statin use is associated with enhanced collateralization of
    severely diseased coronary arteries.

    Pourati I, Kimmelstiel C, Rand W, Karas RH.

    Preventive Cardiology Center, Division of Cardiology, and
    Department of Medicine, New England Medical Center
    Hospitals, Boston, Mass, USA.

    BACKGROUND: The presence of coronary collateral vessels has
    been associated with improved clinical outcome in patients
    with coronary artery disease. Animal experiments have shown
    that hydroxymethyl glutaryl coenzyme A reductase inhibitors
    (statins) can promote angiogenesis in ischemic tissues in a
    cholesterol-independent manner. We hypothesized that statin
    therapy is associated with increased coronary collateral
    formation in patients with severe coronary artery disease.
    METHODS AND RESULTS: Patients undergoing clinically
    indicated coronary angiography at the Tufts-New England
    Medical Center from September 2000 to April 2001 who had at
    least 1 major coronary artery occlusion, or a stenosis of >
    or =95% with Thrombolysis In Myocardial Infarction (TIMI)
    trial grade < or =1 anterograde flow on their angiograms,
    were included. Fifty-one patients were taking statins before
    admission, and 43 patients were not. Their angiograms were
    reviewed and coronary collaterals were graded from 0 to 3
    according to the Cohen-Rentrop method. The statin-treated
    group had a significantly higher mean collateral score
    compared with the patients not taking statins (2.05 vs 1.52,
    P =.005). Multivariate analysis supported the significance
    of the effect of statin therapy on the collateral score.
    There was no relation between collateral score and low-
    density lipoprotein levels (r = -0.06, P =.64). The statin-
    treated group also had a significantly higher left
    ventricular ejection fraction compared to the patients not
    taking statins (51% vs 44%, P <.05). CONCLUSIONS: Statin
    therapy is associated with enhanced coronary collateral
    formation in patients with severely diseased coronary
    arteries. PMID: 14597938

    LIFE-SAVER: World's largest cholesterol-lowering trial
    reveals massive benefits for high-risk patients 13-NOV-2001

    Los Angeles: Around a third of all heart attacks and strokes
    can be avoided in people at risk of vascular disease by
    using statin drugs to lower blood cholesterol levels -
    irrespective of the person's age or

    conclusion of UK researchers who have just completed the
    world's largest randomised trial on cholesterol-lowering
    therapy. Unveiling the key findings today (Tuesday 13
    November) at the American Heart Association's Scientific
    Sessions 2001, lead researcher Professor Rory Collins said:
    "This is a stunning result, with massive public health
    implications. We've found that cholesterol-lowering
    treatment can protect a far wider range of people than was
    previously thought, and that it can prevent strokes as well
    as heart attacks." The MRC/BHF Heart Protection Study (HPS)
    involved 20,000 volunteers aged 40-80 years who were at high
    risk of coronary heart disease, but for whom there was
    substantial uncertainty about the balance of benefits and
    safety of cholesterol-lowering therapy. It specifically
    targeted groups of patients in which there was little direct
    evidence of benefit - including women, the over 70s, people
    with diabetes, those with non-coronary vascular disease, and
    those with average or below-average cholesterol levels.
    Volunteers were allocated either 40mg daily simvastatin as
    cholesterol-lowering therapy, or matching dummy tablets.
    Study treatment and follow-up continued for an average of
    five and a half years in 69 UK hospitals.

    The funding of £21 million (US $32 million) was provided
    by the UK's Medical Research Council (MRC), the British
    Heart Foundation (BHF), and the pharmaceutical companies
    Merck & Co. Inc. and Roche Vitamins Ltd. The study was,
    however, designed, conducted and analysed entirely
    independently of all funding sources by the Clinical Trial
    Service Unit of Oxford University. It started in 1994 and
    ended only last month.

    Summary of major findings o Cholesterol-lowering with statin
    treatment reduces the risk of heart attacks and of strokes
    by at least one-third, as well as reducing the need for
    arterial surgery, angioplasty and amputations.

    o Reductions of at least one-third in these 'major vascular'
    events were found in a very wide range of high-risk patients
    for whom there had previously been uncertainty about using
    cholesterol-lowering therapy:

    o women as well as men;

    o people aged over 70 as well as younger people;

    o people with blood levels of total cholesterol below
    200mg/dl (approx. 5mmol/l) or of 'bad' LDL cholesterol below
    120mg/dl (approx. 3mmol/l), as well as those considered to
    have 'high' levels.

    o About 5 years of statin treatment typically prevents heart
    attacks, strokes or other major vascular events in:

    o 100 of every 1000 people who've previously had a
    heart attack

    o 80 of every 1000 people with angina or some other evidence
    of coronary heart disease

    o 70 of every 1000 patients who've previously had a stroke

    o 70 of every 1000 people with occlusive disease in leg or
    other arteries

    o 70 of every 1000 people with diabetes

    o In addition, cholesterol-lowering reduces the risk of
    being hospitalised because of worsening angina
    - typically, about 30 fewer admissions per 1000 treated
    for 5 years.

    o The benefits increase throughout the study treatment
    period (so more prolonged therapy might be expected to
    produce even bigger benefits), and are additional to
    those of other treatments used to prevent heart attacks
    and strokes.

    o This trial provides uniquely reliable evidence about the
    safety of this simvastatin regimen, with no support for
    previous concerns about possible adverse effects of lowering
    cholesterol on particular non-vascular causes of death, on
    cancers or on strokes due to bleeding.

    Professor Collins, HPS lead investigator, said: "We knew
    from other studies that statins lowered 'bad' LDL
    cholesterol, and reduced heart disease risk in some
    circumstances. But, HPS now provides the first direct
    evidence that cholesterol-lowering therapy cuts the risk of
    heart attacks and strokes by at least one third not just in
    people who already have coronary disease but also in those
    who have diabetes, narrowing of arteries in their legs or a
    previous history of stroke. It shows that, for high-risk
    patients, cholesterol-lowering therapy produces substantial
    benefits even among those considered to have 'low'
    cholesterol levels. It also provides the first clear
    evidence of benefit in women and the over 70s. The study's
    size, and the wide range of high-risk patients included,
    means that doctors now have evidence that is uniquely clear
    and reliable.

    "In this trial, 10 thousand people were on a statin. If now,
    an extra 10 million high-risk people worldwide go onto
    statin treatment, this would save about 50,000 lives each
    year - that's a thousand a week. These results are at least
    as important as previous findings for aspirin's effects on
    heart attack and strokes. Those findings changed medical
    practice, and we expect these to have the same effect. In
    fact, statins are the new aspirin."
     
  10. Zee

    Zee Guest

    > "Zee" <[email protected]hoo.com> wrote in message
    > news:[email protected]...
    > > [email protected] (Zee) wrote in message
    > news:<[email protected]>...
    > > Try your statin here, and keep in mind it is estimated
    > > no more than 10 percent of serious ADRs are ever
    > > reported.
    > >
    > >
    > > B'adant
    >
    > I would think that most serious cases would be recognized
    > via the CPK test, but maybe not reported - I don't know
    > most Drs. habits. But in case of death I would think it
    > would be, but again I'm not sure. Also keep in mind that
    > there are causes other than statins to Rhabdomyolysis and
    > indeed it was known prior to the development of statins.
    >
    > Bill

    Apparently not Bill. It is only a voluntary reporting
    system. And there are many reasons a doctor would
    voluntarily choose not to report. I'll paraphrase a document
    I received recently.

    *Most get their drug information from pharma reps. Many take
    gifts from those same reps including jewellery, computers,
    prommissory notes and trips to luxury resorts. That this
    affects their prescribing habits is incontrovertible: just
    ask the drug company execs who happily put their signature
    to funding of this profitible expense. $$$$

    *Most don't read the warnings from drugs companies or
    medical journals regularly. Some have little training on how
    drugs work, only what they are prescribed for, and do not
    know how common ADRs are or how to recognize them.

    *Many prescribe off-label based on incidental evidence and
    conversations with drugs reps (illegal) and other doctors.

    *Most doctors are paid for service rather than for patient
    so their income goes up if they write more prescriptions
    taking 2 minutes instead of taking more time discussing
    diet, exercise and other options.

    *No doctor ever wants to talk about the primary reason
    doctors don't want to write ADRs--fear of being sued or
    damage to their reputation. They cloud the issue talking
    about the time it takes...

    I'll continue this in a following post.

    B'adant
     
  11. Zee

    Zee Guest

    Top posting for this one. B'adant

    The Washington Times www.washingtontimes.com

    ------------------------------------------------------------
    --------------------

    FDA unaware of most drug complaints By Joyce Howard Price
    THE WASHINGTON TIMES Published March 7, 2004

    ------------------------------------------------------------
    --------------------

    The Food and Drug Administration receives more than
    300,000 reports annually about adverse effects caused by
    drugs on the market, but officials say those reports
    don't include most patients' concerns because local
    health care professionals are not required to report
    complaints to the federal level. "We've always estimated
    we get about 10 percent of all reports," said Dr. Paul
    Seligman, director of the FDA's Office of
    Pharmacoepidemiolgy and Statistical Science. A Harvard
    study two years ago, published in the Journal of the
    American Medical Association, cited previous research
    that estimated only 10 percent of serious adverse
    effects are given to the FDA through its MedWatch
    program. MedWatch is the voluntary system the FDA
    established in 1993 for health professionals to report
    serious adverse reactions and problems related to drugs,
    biologics, medical devices, dietary supplements,
    cosmetics and infant formulas. MedWatch followed another
    FDA voluntary-reporting program started in 1961.
    Pharmaceutical firms are required to report adverse
    effects to the FDA. "Ninety percent of the reports we
    receive about the most adverse effects come from
    manufacturers," said Dr. Seligman, noting that many
    doctors and pharmacists first report such complaints to
    manufacturers.
    Dr. Gregory A. Thompson, director of the Los Angeles County-
    University of Southern California Drug Information
    Center, which advises health care professionals
    about proper dosages and side effects of
    medications, said the proportion of serious drug
    complications voluntarily reported to the FDA is
    "far lower" than 10 percent. "[Health professionals]
    might report 10 percent of people who die of serious
    side effects of drugs," Dr. Thompson said. He
    stressed that there should be more reporting, noting
    that the hospital where he works ?? the USC Medical
    Center ?? "reports hundreds of serious complaints
    yearly" to the FDA. The 2002 Harvard study in JAMA
    found that one in five new drugs produced major side
    effects that were not discovered until after FDA
    approval. The FDA says no one should be surprised
    that it's not until a drug has been taken by
    hundreds of thousands -- or millions -- of people
    that some complications are discovered. One person
    trying to get Congress to require physicians to
    report adverse events after drug approval is Marvin
    Moskowitz, 76, of Lancaster, Calif. He said he took
    a drug for heartburn and developed an unwanted
    condition. "Tissue developed under my breasts, and I
    wanted someone to help me with the $9,000 medical
    bills I incurred," he said. Asked about Mr.
    Moskowitz's push for federal legislation that would
    require physicians to report to the FDA "all serious
    side effects and complications," Dr. Seligman said,
    "the practice of medicine is regulated on a state-by-
    state basis. The FDA has no legal authority over
    health care providers, only manufacturers." A
    spokeswoman for the American Medical Association
    said such a change "would put an incredible burden
    on the health care system."


    > "Zee" <[email protected]> wrote in message
    > news:[email protected]...
    > > [email protected] (Zee) wrote in message
    > news:<[email protected]>...
    > > Try your statin here, and keep in mind it is estimated
    > > no more than 10 percent of serious ADRs are ever
    > > reported.
    > >
    > >
    > > B'adant
    >
    > I would think that most serious cases would be recognized
    > via the CPK test, but maybe not reported - I don't know
    > most Drs. habits. But in case of death I would think it
    > would be, but again I'm not sure. Also keep in mind that
    > there are causes other than statins to Rhabdomyolysis and
    > indeed it was known prior to the development of statins.
    >
    > Bill
     
  12. Anonymous

    Anonymous Guest

    Thanks. In this case the reporting of deaths MAY be somewhat
    higher than typical because there is a good test for the
    condition (CPK) and a known correlation. Of course, one can
    not know for sure.

    Bill
     
  13. George

    George Guest

    All I know is my own Family doctor takes Crestor himself.
    He's late 40's very fit and hates taking meds. It's
    heresay, for sure but he seems to think its safe enough to
    take it himself.
     
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