Antiplatelet therapy use and the risk of venous thromboembolic events in the Raloxifene Use for the Heart (RUTH) trial.
BACKGROUND
Raloxifene use in postmenopausal women with osteoporosis increases the risk of venous thromboembolic events (VTE) 2-fold compared with placebo. Platelet activation is involved in the pathophysiology of arterial thromboses more than venous thromboses, but aspirin may reduce VTE risk associated with estrogen use. This analysis examines the effects of concomitant antiplatelet therapy on VTE risk in raloxifene-treated women.


METHODS
In the Raloxifene Use for the Heart (RUTH) trial, 10,101 postmenopausal women from 177 sites in 26 countries at increased risk of coronary heart disease (CHD) (primary prevention cohort) or with CHD (secondary prevention cohort) were randomized to placebo or raloxifene 60 mg/day and followed for a median 5.6 years. Reports of clinical symptoms of VTE were assessed. Concomitant use of antiplatelet agents (aspirin, clopidogrel, ticlopidine, dipyridamole) was allowed. Cox proportional hazard models, with use of warfarin, presence of fracture, and hospitalization as covariates, were used to estimate hazard ratios (HR) with 95% confidence intervals (CI).


RESULTS
Overall, raloxifene use was associated with an increased VTE risk (HR 1.44, 95% CI 1.06-1.95) vs. placebo. Most women (72%) reported using aspirin, and 14.2% reported using nonaspirin antiplatelet agents during the study period. Users of antiplatelet agents were older, more likely to have CHD, and more likely to be hyperlipidemic. They had a higher VTE risk than nonusers. No difference in VTE risk was observed in women who used raloxifene alone vs. those who used raloxifene with antiplatelet agents during the study. The increase in VTE risk with raloxifene compared with placebo was not different between women who used antiplatelet agents at baseline (HR 1.44, 95% CI 0.98, 2.10) and those who did not use antiplatelet agents (HR 1.37, 95% CI 0.83, 2.27) (interaction p = 0.88). Similar conclusions were noted for aspirin and nonaspirin antiplatelet use.


CONCLUSIONS
In RUTH, postmenopausal women treated with raloxifene had an increased risk of VTE compared with placebo. Concomitant use of aspirin or nonaspirin antiplatelet agents along with raloxifene did not change VTE risk.
Duvernoy
Claire S
CS
VA Ann Arbor Healthcare System/University of Michigan, Ann Arbor, Michigan 48105-2399, USA. duvernoy@umich.edu
Yeo
Adeline A
AA
Wong
Mayme
M
Cox
David A
DA
Kim
Hyungjin M
HM
D001241:Aspirin / Q000627:therapeutic use; D015331:Cohort Studies; D003327:Coronary Disease / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D017698:Postmenopause; D016016:Proportional Hazards Models; D020849:Raloxifene Hydrochloride / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control
D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D001241:Aspirin