The drug raloxifene (Evista®) did not prevent heart problems in postmenopausal women with, or at high risk for, coronary heart disease. The drug did significantly reduce the risk of invasive breast cancer and spinal fractures, but also increased the incidence of blood clots and death from stroke.
Background
Recent large clinical trials have shown that the drug raloxifene, which was originally developed to help prevent osteoporosis, can also reduce the risk of breast cancer in postmenopausal women at high risk of the disease.
In the Multiple Outcomes of Raloxifene (MORE) trial, the drug lowered breast cancer incidence in postmenopausal women with osteoporosis by 72 percent over four years, compared to a placebo. The Study of Tamoxifen and Raloxifene (STAR) trial compared raloxifene to tamoxifen for the prevention of breast cancer in postmenopausal women at increased risk for breast cancer. Both tamoxifen and raloxifene reduced the risk of developing invasive breast cancer by about 50 percent (see the NCI press release about STAR).
The Raloxifene Use for The Heart (RUTH) trial, described in this summary, was originally designed to determine whether raloxifene can reduce the risk of coronary heart disease in postmenopausal women at increased risk for the disease. (Coronary heart disease – damage to the coronary arteries that supply blood to the heart - is the most common form of heart disease.) When results from the MORE trial showed a reduction in breast-cancer risk with use of the drug, the RUTH team expanded their study to look at raloxifene’s breast cancer risk effect, as well.
The Study
The RUTH trial was an international randomized clinical trial designed to determine if raloxifene can reduce the incidence of coronary events and invasive breast cancer in postmenopausal women who had coronary heart disease (CHD) or who were at high risk of CHD. Coronary events included death from a heart attack, from heart failure, or during heart surgery; a nonfatal heart attack; or hospitalization for other heart problems.
Between June 1998 and August 2000, investigators from 26 countries enrolled 10,101 eligible women into the trial. Participating women were randomly assigned to receive either 60 milligrams of raloxifene a day (5,044 patients), or an identical placebo pill (5,057 patients).
Researchers checked on the women’s health status and compliance with their medication schedule twice a year. In addition, an electrocardiography (a test used to measure the condition of the heart) was performed at the beginning of the study, during year 2 and year 4 of follow-up, and during the last follow-up visit. Mammograms and clinical breast examinations were performed at the start and every two years during follow-up. Patients’ cholesterol levels were measured at the beginning of the study, during year 1 and year 5 of follow-up, and during the last follow-up visit.
Investigators recorded occurrences of coronary events; breast cancer; noncoronary events such as stroke and venous thromboembolism (blood clots in the cardiovascular system); bone fractures; and death. Side effects were reported voluntarily by the participants during their checkups.
Results
In both the raloxifene and placebo groups, patients were followed for a median of 5.56 years. About 80 percent of patients in both groups completed the study, and about 70 percent in both groups took at least 70 percent of the assigned medication.
The number of women reporting side effects was not significantly different between the two groups, though more women in the raloxifene group stopped use of the study drug because of side effects.
Investigators did not see any significant differences between the two groups in the number of deaths from coronary causes, nonfatal heart attacks, or hospitalizations for an acute coronary syndrome. These results were unaffected by whether women already had CHD or were at increased risk for CHD.
Levels of low-density lipoprotein (‘bad’) cholesterol declined significantly and levels of high-density (‘good’) lipoprotein cholesterol increased significantly in the raloxifene group. However, these changes did not correspond to a protective effect on the heart.
Raloxifene did reduce the risk of estrogen-receptor positive invasive breast cancer by 55 percent and the incidence of clinical vertebral fractures by 35 percent. The reduction in breast-cancer risk did not differ significantly between women at increased risk and women at normal risk of breast cancer.
However, raloxifene did cause more fatal strokes: 59 women in the raloxifene group (1 percent) and 39 in the placebo group (0.7 percent) died from stroke, which translates into a statistically significant 49 percent higher risk on raloxifene. Similarly, though the absolute numbers were small, women on raloxifene were 44 percent more likely to suffer a noncoronary blood clot than those on placebo.
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