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Barrett-Connor E, Grady D, Sashegyi A, et al. Raloxifene and Cardiovascular Events in Osteoporotic Postmenopausal Women: Four-Year Results From the MORE (Multiple Outcomes of Raloxifene Evaluation) Randomized Trial. JAMA. 2002;287(7):847–857. doi:10.1001/jama.287.7.847
Author Affiliations: Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego, La Jolla (Dr Barrett-Connor); Department of Epidemiology and Biostatistics, University of California, San Francisco (Dr Grady); Lilly Research Laboratories, Indianapolis, Ind (Drs Sashegyi, Anderson, Cox, and Harper); Medical Center, Railway Hospital, Warsaw, Poland (Dr Hoszowski); and Department of Public Health Services, Wake Forest University, Winston-Salem, NC (Dr Rautaharju).
Context Raloxifene, a selective estrogen receptor modulator, improves cardiovascular
risk factors, but its effect on cardiovascular events is unknown.
Objective To determine the effect of raloxifene on cardiovascular events in osteoporotic
Design Secondary analysis of data from the Multiple Outcomes of Raloxifene
Evaluation trial, a randomized, double-blind, placebo-controlled trial conducted
between November 1994 and September 1999.
Setting Outpatient and community settings at 180 sites in 25 countries.
Participants A total of 7705 osteoporotic postmenopausal women (mean age, 67 years).
Intervention Patients were randomly assigned to receive raloxifene, 60 mg/d (n =
2557), or 120 mg/d (n = 2572), or placebo (n = 2576) for 4 years.
Main Outcome Measures Cardiovascular events, including coronary events (myocardial infarction,
unstable angina, or coronary ischemia) and cerebrovascular events (stroke
or transient ischemic attack), collected as safety end points and subsequently
adjudicated by a cardiologist blinded to therapy. Cardiovascular risk at study
entry was determined by the presence of multiple cardiovascular risk factors
or prior coronary events or revascularization procedure.
Results In the overall cohort, there were no significant differences between
treatment groups in the number of combined coronary and cerebrovascular events:
96 (3.7%) with placebo, 82 (3.2%) with 60 mg/d of raloxifene, and 94 (3.7%)
with 120 mg/d of raloxifene. Relative risks (RRs) were 0.86 (95% confidence
interval [CI], 0.64-1.15) and 0.98 (95% CI, 0.74-1.30) for 60 mg/d and 120
mg/d of raloxifene, respectively. Similar results were obtained when coronary
and cerebrovascular events were analyzed separately. Among the subset of 1035
women with increased cardiovascular risk at baseline, those assigned to raloxifene
had a significantly lower risk of cardiovascular events compared with placebo
(RR, 0.60; 95% CI, 0.38-0.95 for both raloxifene groups). The number of cardiovascular
events during the first year was not significantly different across groups
in the overall cohort (P = .94), or among women at
increased cardiovascular risk (P = .86) or with evidence
of established coronary heart disease (P = .60).
Conclusions Raloxifene therapy for 4 years did not significantly affect the risk
of cardiovascular events in the overall cohort but did significantly reduce
the risk of cardiovascular events in the subset of women with increased cardiovascular
risk. There was no evidence that raloxifene caused an early increase in risk
of cardiovascular events. Before raloxifene is used for prevention of cardiovascular
events, these findings require confirmation in trials with evaluation of cardiovascular
outcomes as the primary objective.
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