• Benefit of statin use in women questioned

    May 2010

    An estimated 12 million American women are taking cholesterol-lowering drugs called statins. Many are healthy and just want to lower their cholesterol to help prevent heart disease. However, a recent article in Time magazine calls into question the wisdom of prescribing such drugs to otherwise healthy women.


    “Researchers … don’t know why women are more likely than men to suffer side effects from statins …, but posit that lower body weight and hormonal fluctuations play a role.”
    – Catherine Elton, Time writer
     


    In the article, “Do Statins Work Equally for Men and Women?,” the cases of two women on statins are documented: a healthy woman and one who has diabetes, both with elevated cholesterol. The healthy woman had such severe muscle pain a month after she started taking the drug that she couldn’t sleep. The woman with diabetes suffered memory loss to such an extent that she forgot how to do basic math or drive to familiar places. These symptoms disappeared when the women stopped taking statins.

    While statin therapy can prolong the lives of people with heart disease or delay the onset of heart disease in healthy, at-risk adults, it doesn’t work equally for men and women, the Time article says.

    “Researchers also don’t know why women are more likely than men to suffer side effects from statins and many other drugs, but posit that lower body weight and hormonal fluctuations play a role,” writes Catherine Elton, the author.

    Response to the Time article

    In response to the article, the American Heart Association (AHA) issued a commentary, pointing out that research referred to in Time “demonstrated that the specific categories of women studied benefited (emphasis added) from taking a statin for primary prevention, with a reduction in risk for hospitalizations for unstable chest pain and for important blood vessel operations (surgical or catheterization-based).”

    The AHA reminded patients that the benefits of cholesterol-lowering statins are well-documented. Furthermore, myopathy, or muscle pain, though uncommon, is reversible. They advise against abruptly stopping taking statins without a discussion with a primary care physician.

    JUPITER trial finds benefit for both sexes

    A recently published, sex-specific metaanalysis of the JUPITER trial, which studied men and women who normally wouldn’t be prescribed statins, appears to contradict the claims in Time. Women in the study were age 60 or older, while men were 50 and up. Participants had no history of cardiovascular disease. The subjects all had low LDL cholesterol levels, but elevated levels (≥ 2 mg/L) of the inflammatory marker high-sensitivity C-reactive protein (hs-CRP). High CRP levels have been linked to cardiovascular events. The meta-analysis, which appeared in the Feb. 22, 2010, issue of Circulation, looked at the 13,154 women in the JUPITER trial.

    Researchers found that taking 20 milligrams daily of the statin rosuvastatin (Crestor®) reduced the relative risk of clinical events in women and men to a similar extent (46 percent and 43 percent reduction, respectively). In women, the benefit of rosuvastatin was largely due to reductions in revascularization procedures, such as stent implantations and coronary artery bypass surgery, and also reductions in hospitalization; whereas men also had lower rates of heart attacks and strokes.

    FDA advisory

    A recent statement by the U.S. Food and Drug Administration (FDA) addresses the likelihood of side effects at higher doses of the statin simvastatin (Zocor®), as well as at lower doses when taken with specific other medicines. The FDA recommends that patients be given the minimum effective dosage of that statin to reduce the likelihood of myopathy and rhabdomyolysis, the rapid destruction of skeletal muscles, and that health care providers be aware of the drug interactions when prescribing.

    In its commentary, the AHA states, “It’s important to note that the benefit of lowering cholesterol is most evident in people who have a cardiovascular event such as a heart attack or stroke. The data for statins as preventive treatment for women who have not had a first event, as described in Time, is still building, but results so far tell us that certain women can benefit from more aggressive therapy to avoid a first heart attack or stroke.”

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Page last updated: 5/27/2014 11:56:14 AM
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    What the news means for you

    Biological differences mean drugs affect sexes differently

    Susan S. Smyth, MD
    Cardiologist

    Wright, Heather, MDThere are biological differences between men and women that manifest in health and disease, including cardiovascular disease (CVD). CVD usually occurs earlier in men, appearing roughly 10 years later in women. There are also subtle differences in how the sexes develop and present with their first symptoms of CVD. It is very important to acknowledge that these differences may affect how both sexes respond to cholesterol-lowering or other therapies.


    “For both women and men at high risk, the data is compelling that lowering cholesterol is beneficial and will save lives.” 


    Statins used to lower cholesterol

    When should cholesterol-lowering therapies be considered? First, we try to identify people at the highest risk for a cardiovascular event, such as individuals who have had a heart attack or a stroke or who have peripheral vascular disease or diabetes. For both women and men at high risk, the data is compelling that lowering cholesterol is beneficial and will save lives.

    Next, we consider people who are at risk for a cardiovascular event. Common risk factors include high blood pressure, elevated cholesterol, smoking, a family history of CVD, obesity and inactivity. The JUPITER trial extended the “at risk” group to individuals without symptoms of disease who were otherwise healthy with normal cholesterol levels but who had an elevated inflammatory marker. The data from the JUPITER trial is clear that these individuals also benefit from statin therapy.

    Problems in clinical trials

    In JUPITER, which looked at a group of people without symptoms of disease, there was a reduction of cardiovascular events and death in the population as a whole. When the trial was broken apart to examine events in women and men separately, death was not reduced in either sex. This is because the population of patients was very unlikely to die while in the study. Therefore, the beneficial effect of the drug on death could only be observed when information from men and women was combined. For cardiovascular outcomes other than death, a benefit was observed in both men and women when the sexes were analyzed separately.

    Other clinical trials have failed to demonstrate that statin therapy reduces death in women at risk of CVD. However, the Cholesterol Treatment Trialists examined information from 14 different trials, from 1994 to 2000, and found the reduction in death was the same in both men and women.

    One fundamental issue is that it is difficult to analyze cardiovascular clinical trial data in just women. Women are much less likely than men to be enrolled in clinical trials, so less information is available on how they respond to therapy. Despite a huge push over the last 10 years to recruit women into clinical trials, they are still underrepresented. Among the reasons: Women with cardiovascular disease tend to be older – and their age and other medical conditions may exclude them from trials; women may also be more concerned about the risks of clinical trials and therefore be less likely to be willing to participate.

    Risks and benefits

    Cholesterol-lowering therapy should be tailored to an individual. Physicians strive to identify people who are most likely to suffer from CVD, benefit the most and have a low likelihood of side effects. Women are often older when they present with CVD and they also tend to weigh less than men. Age and weight can be important features that determine how a person will respond to drug therapy. Thus, it would not be surprising for side effects from a particular cardiovascular drug to be different in women and men.

    Statin therapy comes with some very rare but serious side effects, such as liver failure and acute muscle breakdown (rhabdomyolysis). The side effects usually resolve when the drug is discontinued. At this time, I know of no reason to deny statin therapy to a high-risk or at-risk woman solely based on her sex. In my practice, I am now checking hs-CRP levels to provide additional information for women and men on their risk of suffering a cardiovascular event.


    “Women are often older when they present with CVD and they also tend to weigh less than men. Age and weight can be important features that determine how a person will respond to drug therapy.” 


    While CVD is the leading killer in people, it does not kill everyone. We don’t need to treat everyone. We do need to improve our ability to personalize medicine by identifying women and men who are most likely to benefit from a therapy. We also need to do a better job at preventing CVD. All women should try to exercise 30 minutes a day; eat a diet rich in vegetables, whole grains, and fish; and limit their intake of saturated fats (<10% of calories), cholesterol (<10% of calories), cholesterol (<300 mg/ day) and salt (< 1 – 2 grams/day).

    Dr. Smyth is a cardiologist with the UK Gill Heart Institute and the Lexington Veterans Administration Medical Center, as well as an associate professor of medicine in the UK College of Medicine.

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