Orlando, FL - Unlike hormone replacement therapy (HRT), treatment with the selective estrogen receptor modulator (SERM) raloxifene appears to be associated with neither an early increase, nor a late decrease in cardiovascular (CV) events. The results, taken from the Multiple Outcomes of Raloxifene Evaluation (MORE) study of raloxifene for osteoporosis, were presented here at the American College of Cardiology 50th Annual Scientific Session.

"I think what we can say is that in people who are not at particularly high risk of heart disease, there's no evidence of harm," said Dr Elizabeth Barrett-Connor (UCSD). No benefit was apparent either, she said, although the average age of women in the study was 67, and treatment longer than 3 years might be required to see any benefit in these patients.

MORE data

In the MORE study, researchers were investigating the effects of raloxifene on osteoporosis in 7705 women - specifically, the incidence of fractures, and changes in bone mineral density (BMD). Women were randomized to one of three groups, placebo, or raloxifene in doses of 60 mg (now the recommended dose in this indication) and 120 mg per day. The main results of that study showed that raloxifene significantly reduced spinal fractures.

Although CV events were not the main focus of this trial, they were recorded as safety endpoints. All CV events were adjudicated by a cardiologist, who was blinded to treatment assignment, and not associated with the trial. Only 2% had known heart disease at enrollment.

Serum lipids were evaluated at baseline and after treatment. Both doses of raloxifene significantly reduced both total cholesterol and LDL cholesterol, Barrett-Connor reported. HDL cholesterol increased equally and "mysteriously" across all three groups, but was not significantly increased unlike it is with estrogen therapy, she added. Also unlike HRT, triglycerides were not raised by raloxifene.

One novel finding was a "rather striking" reduction in fibrinogen, "which would be presumed to be a beneficial effect."

Cardiovascular events

Over 3 years, 205 women reported at least one CV event, including 116 coronary events, 20 coronary deaths, 29 nonfatal MIs, 50 UA, 19 coronary ischemia on ECG, and 89 cerebrovascular events.

"The bottom line is that if you take all cardiovascular events, all coronary and cerebrovascular events, there is no evidence of harm or benefit in this study," Barrett-Connor said.


Number of events at 1 year with 60 mg raloxifene therapy versus placebo

Events Placebo Raloxifine 60 mg RR (95% CI) Coronary events 15 18 1.22 (0.62-2.41) Cerebrovascular events 8 7 0.89 (0.32-2.45) All CV events 23 25 1.10 (0.63-1.94)

Number of events at 3 years with 60 mg raloxifene therapy versus placebo

Events Placebo Raloxifine 60 mg RR (95% CI) Coronary events 39 34 0.88 (0.56-1.39) Cerebrovascular events 32 29 0.91 (0.55-1.50) All CV events 17 63 0.89 (0.64-1.25)

Number of events at 1 year with 120 mg raloxifene therapy versus placebo

Events Placebo Raloxifine 120 mg RR (95% CI) Coronary events 15 13 0.87 (0.42-1.83) Cerebrovascular events 8 10 1.26 (0.50-3.18) All CV events 23 23 1.01 (0.57-1.79)

Number of events at 3 years with 120 mg raloxifene therapy versus placebo

Events Placebo Raloxifine 120 mg RR (95% CI) Coronary events 39 43 1.10 (0.72-1.70) Cerebrovascular events 32 28 0.88 (0.53-1.45) All CV events 17 71 1.00 (0.72-1.39)

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Even among the 202 women with established coronary disease at baseline, there were no apparent differences on these parameters, although numbers were small.

Cardiac effects of raloxifene "important"

Besides the antiosteoporotic effects of raloxifene, there is also some evidence that it may reduce breast cancer, perhaps by as much as 90%, Barrett-Connor noted. "It's very important that we know whether it's good or bad for your heart because there were big surprises with estrogen."

	It's very important that we know whether it's good or bad for your heart because there were big surprises with estrogen.

To better define some of these issues, the results of the Raloxifene Use for The Heart (RUTH) study, an international study comparing raloxifene to placebo are awaited with "great curiosity," she added. Enrollment for the study was recently completed, in total 10 101 postmenopausal women at increased risk for coronary events. Two primary outcomes for the trial include a cardiovascular endpoint, the combined incidence of nonfatal MI, fatal coronary disease, and hospitalization for acute coronary syndromes, and a separate endpoint of invasive breast cancer. Results are expected in 5 to 7 years' time.

Susan Jeffrey sjeffrey@conceptis.com

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