Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During this year, cellular therapy with bone mononuclear cells of critical leg ischemia was demonstrated to be a new therapeutic approach in critical leg ischemia. This treatment, as well as gene therapy, is an important step forward in this pathology when there is no other therapeutic option. In venous thromboembolism, the usefulness of fibrinolytic therapy in severe pulmonary embolism associated with right ventricular dysfunction or pulmonary-artery hypertension was demonstrated. Fondaparinux appears also to be a promising agent for prophylaxis of deep vein thrombosis. Finally, the publication of the WHI trial (Women Health Initiative) confirms the absence of any benefit of hormone replacement therapy in primary cardiovascular prevention.
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PMID:[The best of vascular medicine in 2002]. 1261 66

(1) The WHI study was published in 2002: a randomised double-blind placebo-controlled clinical trial in more than 16 000 women with an average age of 63 years at enrollment. The paper reports data on the long-term adverse effects of combined equine estrogen-progestin hormone replacement therapy, taken for 5 years. (2) On average, a yearly excess of 19 severe adverse events per 10 000 women occurred in the estrogen-progestin group. Relative to the placebo group, there were an extra 8 pulmonary embolisms, 7 coronary events, 8 strokes and 8 cases of invasive breast cancer. In contrast, there were 6 fewer colorectal cancers and 5 fewer hip fractures in the active treatment group. (3) The differences in the frequency of coronary events and venous thromboembolism emerged after the first year of treatment, while the curves for stroke and breast cancer diverged after the second and fifth years, respectively. (4) The overall mortality rate did not differ between the two groups. (5) A placebo-controlled trial of the same hormone combination (HERS trial), given for 4.1 years as secondary prophylaxis against coronary heart disease was published in 1998. The drug was ineffective during the trial, and during unblinded post-trial follow-up of 2 321 women for an average of 2.7 years (HERS II study). (6) The estrogen-progestin combination used in these trials did not reduce the risk of coronary heart disease (in primary or secondary prophylaxis) or the risk of stroke. On the contrary, both risks increased. (7) The increased incidence of deep venous thrombosis and/or pulmonary embolism associated with estrogen-progestin replacement therapy was confirmed in these trials, even among women with no relevant history. (8) The WHI trial also confirmed the increased risk of breast cancer in women on hormone replacement therapy, but did not study its impact on outcome or mortality. (9) The WHI trial confirmed the beneficial impact of estrogen-progestin combination therapy on the risk of osteoporotic fracture. An average of 5 hip fractures were avoided each year per 10 000 women treated (10 versus 15 observed cases per 10 000 women per year), together with 6 symptomatic vertebral fractures (9 versus 15 cases) and 44 osteoporotic fractures (147 versus 191 cases). It is not known whether the benefit observed at the end of the trial persisted after the end of treatment. (10) In practice, the decision to prescribe hormone replacement therapy, and the optimal duration of treatment, must be weighed up according to each individual's risk factors. And the decision to treat or not to treat must be regularly re-assessed. Women must be informed of the potential risks and benefits, and must be monitored. They should also be advised not to use less well assessed treatments such as phytoestrogens, DHEA and tibolone. (11) Health authorities, especially in Europe, must organise comparative trials to assess the benefits and risks of other hormone combinations used by perimenopausal and postmenopausal women.
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PMID:Postmenopausal hormone therapy: cardiovascular risks. 1267 30

(1) The results of a randomised placebo-controlled double-blind trial in 16 000 women (the WHI trial), published in 2002, showed that post-menopausal hormone replacement therapy based on sulphoconjugated equine oestrogen and medroxyprogesterone led to an excess risk of serious adverse events (pulmonary embolism, coronary events, stroke, and invasive breast cancer). (2) Further analysis showed that invasive breast cancer diagnosed in women treated with the hormone combination had a similar histology and grade to cancers diagnosed in the placebo group, but that they were larger and more advanced. (3) The excess risk of stroke was mainly due to ischaemic events. In the group treated with the hormone combination, the only identifiable risk factor was lengthy use of hormone replacement therapy before enrollment in the trial. (4) No subgroup of women at risk of coronary events was found apart from women with elevated LDL-cholesterol at enrollment. (5) In the WHIMS subtrial in women aged 65 years or more, the risk of dementia was twice as high in women receiving hormone therapy as in those receiving placebo. (6) In the British ESPRIT placebo-controlled trial, oral estradiol valerate, at a dose of 2 mg/day, was ineffective as secondary prevention of myocardial infarction. (7) Follow-up of a very large British cohort (the Million Women Study) showed a significantly increased risk of breast cancer with all types of hormone replacement therapy, including oestrogen-progestin combinations (relative risk 2.00; 95% confidence interval 1.88-2.12), oestrogen monotherapy (RR 1.30; 95% CI 1.21-1.40) and tibolone (RR 1.45; 95% CI 1.25-1.68). There was no significant difference between oestradiol and equine oestrogen, between medroxyprogesterone acetate and progestins derived from nortestosterone, between oral, transdermal and implanted oestrogen preparations, or between sequential and continuous regimens. (8) A Swedish cohort study and an American case-control study also showed a higher risk of breast cancer linked to progestin use. (9) In a small French epidemiological case-control study, the risk of thromboembolism was higher among women taking oral rather than transdermal estradiol as part of their hormone replacement therapy. (10) In practice, the risk-benefit ratios of the hormone replacement therapies most commonly used in France are poorly characterised. It is therefore logical to use the drugs with which we have most experience (in clinical trials or during lengthy follow-up). The benefits and drawbacks should be regularly discussed with women using hormone replacement therapy, and they should be closely monitored for signs of breast cancer or cardiovascular disease.
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PMID:Post-menopausal hormone replacement therapy (cont'd): risk-benefit balance in the hot seat. 1523 53