Prescrire International最新文献

Dabigatran, an oral anticoagulant that acts by inhibiting thrombin, was first marketed in the European Union in 2008. No antidote has been available, complicating the management of patients who have severe bleeding or require emergency surgery. In late 2015, idarucizumab, a monoclonal antibody directed against dabigatran, was authorised in the European Union as a specific antidote for dabigatran. It is administered intravenously. In early 2016, most data on the efficacy of idarucizumab come from an interim analysis of a non-comparative trial in 123 dabigatran-treated patients who had serious bleeding or required emergency surgery or invasive procedures. All 123 patients received idarucizumab. Twenty-six patients died, 8 from bleeding. Among the 66 patients with bleeding, the duration of the event could not be determined in 18 cases because the site of bleeding was not visible. Among the other 48 patients, the bleeding stopped in 44 cases after a median of about 10 hours. Fifty-two of the 57 patients who received idarucizumab prior to invasive procedures underwent surgery. The surgeons considered their clotting status to be normal in 48 cases and mildly or moderately abnormal in the other 4 cases. The role of idarucizumab in these outcomes is difficult to assess for several reasons, including: the lack of a comparator; the partly subjective end-points as the use of idarucizumab was known; and failure to take into account the natural rate of dabigatran elimination. Although idarucizumab normalised markers of dabigatran activity in most patients, the clinical impact was not reported in terms of the frequency of bleeding or thrombosis. The EU summary of product characteristics states that a second dose of idarucizumab can be administered in case of marked dabigatran exposure (massive ingestion, severe renal impairment), but this was the case for only two patients included in the clinical trial. Few data on the adverse effects of idarucizumab are available. Idarucizumab carries a risk of hypersensitivity reactions and of developing anti-idarucizumab antibodies, with unknown consequences. In practice, in 2016, close monitoring of patients on dabigatran and standard management of bleeding and its consequences remain the priority. The clinical effects of idarucizumab are poorly documented. Authorisation of this antidote should not lead to trivialising the use of dabigatran. In 2016, warfarin, a vitamin K antagonist, is the standard oral anticoagulant for most patients, despite its inconvenience.

Patients with relapsed or refractory multiple myeloma who have received several lines of therapy have no satisfactory treatment options. High-dose corticosteroid therapy or a combination of low-dose dexamethasone and pomaildomide may be proposed. Panobinostat is the first histone deacetylase (HDAC) inhibitor to be authorised in the European Union for use in this indication. A randomised, double-blind, placebo-controlled trial evaluated panobinostat in 768 patients with relapsed or refractory multiple myeloma who were also receiving bortezomib + dexamethasone. Panobinostat did not prolong survival. The median time to myeloma progression, relapse, or death was prolonged by about 3 months with the panobinostat-containing combination, and by a median of about 8 months in the subgroup of patients who had received at least two lines of chemotherapy including bortezomib and an "immunomodulatory" drug. There was no statistically significant increase in survival, however. In this trial, adverse events led one in six patients to discontinue panobinostat and resulted in numerous hospital admissions. The proportion of patients who died from causes unrelated to myeloma was 6.8% in the panobinostat group versus 3.2% In the placebo group. The toxicity of panobinostat affects most vital functions, resulting in a risk of infections as well as haematological, gastrointestinal, cardiac, renal, hepatic and thyroid disorders. These adverse effects are often severe and sometimes fatal. Panobinostat is subject to pharmacokinetic interactions via cytochrome P450 enzymes and P-glycoproteln, and also to pharmacodynamic Interactions. Panobinostat was teratogenic in animal studies. In practice, even when several previous lines of treatment have failed, panobinostatis more toxic than useful In patients with myeloma. It should therefore not be used.

In an unblended trial in 1623 multiple myeloma patients, treatment with lenalidomide + dexamethasone until disease progression appeared to prolong survival by a few months more than with the thalidomide + melphalan + prednisone combination given for 18 months, but serious adverse effects were more frequent.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterised by largely irreversible changes in air flow due to irritants such as tobacco smoke. Patients with COPD experience acute exacerbations. Severe disease may progress to chronic respiratory failure. We reviewed the literature on basic medications available for COPD, using the standard Prescrire methodology. There are few clinical data on treatment of mild COPD. Regular medication is not necessary for patients who do not have recurrent symptoms. Eliminating exposure to cigarette smoke and other irritants such as workplace irritants, is the only measure known to improve the outcome of COPD. Evaluation of inhaled short-acting beta-2 agonists is based mainly on short-term trials. These drugs have been shown to improve dyspnoea. Salmeterol and formoterol, two long-acting beta-2 agonists, have been extensively evaluated in symptomatic patients. Compared with no treatment, these drugs reduce breathlessness and acute exacerbations, preventing about two hospital admissions per 100 patients with moderate to severe COPD treated for 7 months. Indacaterol and olodateroldo not have a better harm-benefit balance. Inhaled beta-2 agonists occasionally provoke cardiovascular disorders. No excess mortality has been reported among the thousands of COPD patients included in clinical trials. There Is little evidence that ipratropium, an inhaled short-acting anti-muscarinic bronchodilator, improves COPD symptoms. A risk of Increased mortality among COPD patients treated with ipratroplum cannot be ruled out. Tiotroplum, an inhaled long-acting antimuscarinic bronchodilator, has been extensively evaluated In COPD. Tiotroplum has symptomatic efficacy in COPD, reducing dyspnoea and acute exacerbations. Tiotroplum had no tangible advantages over long-acting beta-2 agonists in seven randomised trials including more than 12 000 patients. Glycopyrronium and aclidinium, two other Inhaled long-acting antimuscarinics, do not appear to be more effective. Tiotroplum, like other inhaled anti-muscarinics, has antimuscarinic adverse effects including cardiac, visual and buccal disorders. Glycopyronium may carry a higher risk of serious cardiovascular effects. Combination of an antimuscarinic with an inhaled beta-2 agonist improves symptoms in 7% to 10% of patients. In patients with one or two COPD exacerbations per year, adding an Inhaled corticosterold (beclometa- sone, budesonide or fluticasone) to a long-acting beta-2 agonist prevents about 1 exacerbation during 3 to 4 years of treatment. Inhaled corticosteroids can cause pneumonia, candidiasis, dysphonia and adrenal Insufficiency. Fluticasone seems to have more adverse effects than other inhaled corticosterolds. Theophylline has uncertain efficacy on symptoms of COPD. This drug has a narrow therapeutic index and carries a risk of serious adverse effects. It should not be used in COPD. Long-term treatment with roflumilast or oral corticosteroids h