Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Raloxifene, a selective estrogen receptor modulator (SERM) licensed for the prevention of non-traumatic vertebral fractures in postmenopausal women at increased risk of osteoporosis, was launched in the UK in August 1998. The aim of the study was to monitor the safety of raloxifene prescribed in the primary care setting in England using prescription-event monitoring (PEM). Patients were identified by means of prescription data supplied by the Prescription Pricing Authority between September 1998 and November 2000. Demographic and clinical event data were collected from questionnaires posted to primary care physicians (GPs) at least 6 months after the date of the first prescription for each patient. Information on medical events, suspected adverse drug reactions (ADRs), reasons for stopping treatment, pregnancies, and causes of death was requested. Event rates [Incidence Densities (IDs): no. first reports /1000 patient-months of treatment] were calculated. Differences between IDs for events reported in month one (ID(1)) and months 2-6 (ID(2-6)) of treatment were examined. The cohort comprised 13,987 patients [median age 62 years (IQR 55,69); 99.8% female]. The major indication was osteoporosis (40.9%, n=5725). Flushing was the event with the highest ID in month 1 (22.8), reported most frequently by GPs as an ADR to raloxifene (67/461 reports) and as the reason for stopping (700/4592 reports). Events associated with starting treatment included flushing, malaise/lassitude, headache/migraine, nausea/vomiting, sweating, cramp, pain abdomen, dizziness, diarrhea, mastalgia and vaginal hemorrhage. Less common events reported during treatment included deep vein thrombosis (n=13), pulmonary embolism (n=13), thrombophlebitis (n=31) and visual disturbance (n=29). In this study, there were 122 (0.9%) confirmed deaths, of which 32 causes of death were unknown. This study shows that raloxifene is generally well tolerated when used in general practice in England. Potential signals of unrecognised ADRs requiring further evaluation included gastrointestinal adverse symptoms and vaginal hemorrhage. There were also a small number of reports of events associated with venous thromboembolism and visual disorders that require further investigation.
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PMID:Safety profile of raloxifene as used in general practice in England: results of a prescription-event monitoring study. 1530 82

Raloxifene is the first Selective Estrogen Receptor Modulator (SERM) approved for the prevention and treatment of osteoporosis in postmenopausal women. Acting as an estrogen agonist in the skeleton and on lipid metabolism, raloxifene maintains bone mineral density (BMD) and prevents new vertebral fractures while improving the lipid profile in postmenopausal women. In an osteoporosis prevention study, 601 women without osteoporosis, aged 45 to 60 years, were assigned to receive a placebo or raloxifene 30, 60, or 150 mg/day. All women received calcium (400 to 600 mg/day). Raloxifene 60 mg increased BMD by 2.4% at both the lumbar spine and hip compared with the placebo at 36 months. More importantly, however, raloxifene significantly reduced the risk of new vertebral fractures in Multiple Outcomes of Raloxifene Evaluation (MORE), a placebo-controlled, double-blind randomized trial of 7705 postmenopausal women with osteoporosis. The women, with a mean age of 66.5 years, and with hip or spine T-score <-2.5 and/or prevalent vertebral fractures, were assigned to receive either a placebo or 60 mg or 120 mg of raloxifene. All women were provided supplemental calcium (500 mg/day) and vitamin D (400 IU/day). After 36 months, raloxifene 60 mg/day and 120 mg/day, reduced the risk of new vertebral fractures by 55% (RR 0.45, 95% CI 0.3, 0.7; p<0.001), and 40% (RR 0.60, CI 0.4, 0.9) in women without prevalent baseline fractures, respectively; and by 31% (RR 0.7, 95% CI 0.6, 0.9; p<0.001), and 49% (RR 0.5, CI 0.4, 0.6) in women with prevalent baseline fractures compared with the placebo. There was no difference in the proportion of women reporting non-traumatic, non - spine fractures among women receiving raloxifene compared to the placebo-treated women. Compared with placebo, BMD increased after 36 months by 2.1 and 2.6% at the femoral neck and spine, respectively, in the 60mg raloxifene group, and by 2.4 and 2.7% at the femoral neck and spine, respectively, in the 120mg raloxifene group. By 40 months of follow-up, there was a higher rate of deep venous thrombosis (38 cases) and pulmonary embolus (17 cases) in the combined raloxifene groups than in the placebo group (5 and 3 cases,), with a relative risk of 3.1, (CI 1.5-6.2). By 40 months, 54 women had a confirmed diagnosis of breast cancer with a relative risk compared to placebo of 0.35, (CI, 0.21-0.58). Raloxifene therapy for 3 years maintains BMD in healthy postmenopausal women and significantly reduces the risk of new vertebral fractures by about half in postmenopausal women with osteoporosis. Raloxifene also reduces the risk of breast cancer by 65% in postmenopausal women with osteoporosis thus providing a new choice for addressing postmenopausal health concerns.
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PMID:Raloxifene: results from the MORE study. 1575 5

In 1998, the concept of breast cancer prevention became a reality with the approval of tamoxifen to reduce the risk of developing breast cancer in women at increased risk for the disease. This approval was based on decades of research on selective estrogen receptor modulators providing an understanding of the role of the estrogen receptor in breast cell growth, and an appreciation of the carcinogenic process. Although results from the Breast Cancer Prevention Trial demonstrated a 49% reduction in breast cancer in women at increased risk, there were associated toxicities related to the estrogenic effects of tamoxifen; that is, deep vein thrombosis, pulmonary embolism, and endometrial cancer. In an effort to improve its benefit-risk profile, tamoxifen is now being compared with raloxifene, a selective estrogen receptor modulator approved for the treatment and prevention of osteoporosis. This equivalency prevention Study of Tamoxifen and Raloxifene completed accrual of 19 747 high-risk postmenopausal women in November 2004. Meanwhile, another class of estrogen-directed drugs, the aromatase inhibitors, have shown efficacy in breast cancer adjuvant trials, spawning a number of prevention trials that have recently been initiated. As with breast cancer the hormonal contribution to prostate carcinogenesis was the basis for the Prostate Cancer Prevention Trial which showed that finasteride, an androgen antagonist, reduces the incidence of prostate cancer compared to placebo.
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PMID:Hormonal interventions to prevent hormonal cancers: breast and prostate cancers. 1741 94

Raloxifene, a selective estrogen receptor modulator, is indicated for the prevention of osteoporosis in postmenopausal women. However, its effect on the risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) is unclear. Therefore, we conducted a meta-analysis to evaluate the effect of raloxifene on these outcomes. To identify randomized controlled trials of raloxifene, a systematic search of PubMed, EMBASE, and Cochrane Collaboration databases was performed from the date of inception of these databases to October 2007. Search was limited to trials that were published in peer-reviewed English-language medical journals. Articles were included in the meta-analysis if they had reported on DVT, PE, or thromboembolic events. Nine trials, including 24,523 postmenopausal women, (median age 59.4 years, range 55 to 67 years; median follow-up 24 months, range 3 to 67 months) met inclusion criteria. Therapy with raloxifene was associated with a 62% increase in odds of either DVT or PE (odds ratio = 1.62; 95% confidence interval = 1.25 to 2.09; p-value < 0.001). Similarly, raloxifene therapy was associated with 54% increase in odds of DVT (odds ratio = 1.54; 95% confidence interval = 1.13 to 2.11; p-value = 0.006) and 91% increase in odds of PE alone (odds ratio = 1.91;95% confidence interval = 1.05 to 3.47; p-value = 0.03). Raloxifene increases the risk of DVT and PE in postmenopausal women.
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PMID:Effect of raloxifene therapy on venous thromboembolism in postmenopausal women. A meta-analysis. 1827 83

Selective estrogen receptor modulators (SERMs) have offered the promise of reducing the burden of coronary artery disease (CAD) in postmenopausal women, based on the positive effects recorded on intermediate markers (blood lipids and markers of inflammation). The effects of raloxifene, bazedoxifene and lasofoxifene on cardiovascular endpoint markers are presented as reported in recent, randomized, controlled trials. Raloxifene failed to significantly lower the risk of CAD in postmenopausal osteoporotic women, without any effect on stroke or early harm, but doubling the risk of venous thromboembolism. The risk of CAD was lowered in a subgroup of patients at risk of CAD. In a large randomized, controlled trial with CAD as the primary endpoint in patients at risk of CAD, raloxifene failed to significantly reduce CAD, while significantly increasing the incidence of fatal stroke and venous thromboembolism. Bazedoxifene, in an osteoporosis trial, had similar effects on the cardiovascular system when compared to raloxifene. Lasofoxifene has only been studied in postmenopausal osteoporotic women in the PEARL trial. Lasofoxifene reduced the risk of coronary heart disease events as well as the risk of stroke, while the risk of deep vein thrombosis remained in line with other SERMs. These results will need to be confirmed in a study with primary cardiovascular endpoints. Until then, it is unlikely that SERMs will play a major role in strategies aimed at the prevention of coronary heart disease in postmenopausal women.
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PMID:Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women. 1981 Dec 53