Patients Who Switched from Established Lipitor Therapy to Simvastatin Experienced a Significant 30 Percent Increase in Relative Risk of Cardiovascular Events or Death, New Observational Study Shows



    An observational study of a large United Kingdom primary care
    database showed that switching patients from Pfizer's Lipitor(R)
    (atorvastatin calcium) Tablets to simvastatin was associated with a 30
    percent increase in the relative risk of major cardiovascular events,
    including heart attacks, strokes and certain types of heart surgeries,
    or death compared to patients who remained on Lipitor therapy.

    This analysis was presented today at the European Society of
    Cardiology Congress 2007 and is also in press at The British Journal
    of Cardiology.

    The data, which included records from October 1997 to June 2005,
    were generated from a retrospective analysis of a medical database of
    anonymous patient records entered by general practitioners in the
    United Kingdom known as The Health Improvement Network (THIN). The
    analysis included 11,520 patients (2,511 patients who had taken
    Lipitor for six months or more and were switched to simvastatin vs.
    9,009 patients who were taking Lipitor for six months or more and then
    remained on Lipitor therapy). Reasons for switching were not available
    from the database. Since patients were not randomly assigned to each
    group, the two treatment groups were matched based on certain risk
    factors and statistical adjustments were made to address any residual
    imbalances. As with all observational studies, the findings should be
    regarded as hypothesis generating.

    "Today, many health care payors including governments and managed
    care companies are encouraging patients who are well-established on
    one therapy to switch to a different statin therapy," said Dr. Michael
    Berelowitz, senior vice president of Pfizer's global medical division.
    "This study raises concerns about those policies. It suggests the
    potential for poorer cardiovascular outcomes associated with switching
    patients from established Lipitor therapy to simvastatin."

    A secondary analysis of the same data showed that patients who
    were switched from Lipitor to simvastatin were more than twice as
    likely to discontinue their treatment compared to those who remained
    on Lipitor therapy (20.5 percent versus 7.62 percent, p(less
    than)0.001). The reasons for discontinuation were not available from
    the database, though disruption in treatment has been associated with
    poor adherence in previous studies of statins and other medications.

    "The results of this analysis complement the large body of
    evidence from multiple clinical trials demonstrating the
    cardiovascular benefits of Lipitor," said Dr. Berelowitz.
    "Observational studies help the medical community better appreciate
    what is really happening in doctors' offices, and are commonly used by
    healthcare payors to set medical practice guidelines. This analysis
    highlights the need to carefully consider individual patient
    circumstances and cardiovascular risk because indiscriminate switching
    may adversely affect some patients."

    Additional Study Information

    The primary endpoint was time to a first major cardiovascular
    event, defined as heart attack, stroke, or coronary revascularization
    (a type of heart surgery), or all-cause death. There was a
    statistically significant 30 percent increase in the relative risk of
    the primary endpoint (p=0.03).

    -- The individual components making up the primary endpoint were
    analyzed as secondary endpoints. Compared with patients who
    did not switch therapy, switching was associated with the
    following:

    -0-
    *T
    -- Significant 43 percent increase in the relative risk of
    major cardiovascular events (p=0.008)

    -- No difference in all-cause death (p=0.369)
    *T

    -- The two treatment groups were matched based on the following:
    gender, history of heart attack, diabetes, time since last
    statin exposure and general practitioner treatment center.

    -- The following statistical adjustments were made to address any
    residual imbalances: age, gender, prior statin exposure, time
    since last statin exposure, diabetes, history of heart attack,
    and baseline cholesterol levels.

    -- Relative risk is the ratio of the risk of major cardiovascular
    events or death occurring in the group who switched from
    Lipitor to simvastatin versus the risk in the group who
    remained on Lipitor.

    About Lipitor

    Lipitor is the only statin with all the following criteria most
    important for many physicians, patients and payors: significant and
    proven cardiovascular event reductions, impressive average LDL
    lowering of 39 percent to 60 percent, and a proven safety profile
    across a broad range of patients.

    Lipitor is the most prescribed cholesterol-lowering therapy in the
    world, with nearly 139 million patient-years of experience. It is
    supported by an extensive clinical trial program involving more than
    400 ongoing and completed trials with more than 80,000 patients. There
    have been more than ten cardiovascular outcomes trials with more then
    50,000 patients.

    Important Safety Information

    Lipitor is a prescription medication. It is used in patients with
    multiple risk factors for heart disease such as family history, high
    blood pressure, age, low HDL ("good" cholesterol) or smoking to reduce
    the risk of heart attack, stroke, certain kinds of heart surgery, and
    chest pain. When diet and exercise alone are not enough, Lipitor is
    used along with a low-fat diet and exercise to lower cholesterol.

    Lipitor is also used in patients with type 2 diabetes and at least
    one other risk factor for heart disease such as high blood pressure,
    smoking or complications of diabetes, including eye disease and
    protein in urine, to reduce the risk of heart attack and stroke.

    Lipitor is not for everyone. It is not for those with liver
    problems. And it is not for women who are nursing, pregnant or may
    become pregnant.

    Patients taking Lipitor should tell their doctors if they feel any
    new muscle pain or weakness. This could be a sign of rare but serious
    muscle side effects. Patients should tell their doctors about all
    medications they take. This may help avoid serious drug interactions.
    Doctors should do blood tests to check liver function before and
    during treatment and may adjust the dose. The most common side effects
    are gas, constipation, stomach pain and heartburn. They tend to be
    mild and often go away.

    For additional product information, visit www.Lipitor.com.