Tiotropium Respimat increases the risk of mortality: pro

Abstract

@ERSpublications Tiotropium Respimat increases mortality risk. First do no harm. Tiotropium Respimat should not be prescribed in COPD http://ow.ly/mzPGL Systematic reviews and meta-analyses of randomised controlled trials of medications provide a high standard of evidence to inform clinical practice, and can be considered the ''gold standard'' for assessing the risk/benefit profile of treatments [1,2]. Three systematic reviews and meta-analyses (including a Cochrane Review) of randomised placebo-controlled trials of tiotropium Respimat, each using different methods, have demonstrated a 50% increased risk of mortality, with its use in patients with chronic obstructive pulmonary disease (COPD) [3][4][5]. These analyses provide substantive evidence that tiotropium Respimat increases mortality in the treatment of COPD [6,7]. It is informative to review each of the systematic reviews and the issues that have been raised relevant to their interpretation.In 2011 the British Medical Journal (BMJ) published the first systematic review and meta-analysis, which included all parallel-group, randomised, placebo-controlled trials of tiotropium Respimat in the treatment of COPD that had reported data on mortality and were of a minimum 30-day duration [3] (table 1 [ [8][9][10]). Five trials were included in the analysis, two 12-week trials and three 12-month trials, studying 6522 participants. All five trials were judged to be at low risk of bias. Tiotropium Respimat significantly increased the risk of all-cause mortality, relative risk 1.52 (95% CI 1.06-2.16). There was an apparent dose-response effect on all-cause mortality, with RR 1.46 (95% CI 1.01-2.10) and 2.15 (95% CI 1.03-4.51), for the 5-mg and 10-mg preparations, respectively ( fig. 1). The overall estimates were not substantially changed by sensitivity analyses using the random effects model, limiting the analysis to three trials of 1-year duration period each, or the inclusion of additional preliminary data on tiotropium Respimat from an unpublished study. An accompanying editorial calculated, based on these figures, that one excess death is expected for every 121 (COPD) patients treated with a 5 mg dose of tiotropium by Respimat for 12 months [11].The 2012 Cochrane Review of tiotropium included the same five randomised placebo-controlled clinical trials of tiotropium Respimat, but used the Peto method for pooled estimation of odds ratio, which is arguably more appropriate for the combined analysis of rare events such as death [4]. Tiotropium Respimat significantly increased the risk of mortality, OR 1.47 (95% CI 1.04-2.08). In contrast there was no increased risk of mortality with tiotropium HandiHaler, OR 0.92 (95% CI 0.80-1.05).In 2012 Thorax published a systematic review with direct comparison and mixed treatment comparison meta-analyses of randomised controlled trials of medications used in the treatment of COPD that provided data about overall or cardiovascular death, and were a minimum 6 months in trial duration [5]. In the direct comparison meta-analysis, ti...

Use of tiotropium RespimatversusHandiHaler and mortality in patients with COPD

“…These disturbing findings are in accordance with the relatively high prevalences of arrhythmia, ischaemic heart disease and renal failure in our cohort study on the association between use of tiotropium Respimat versus use of tiotropium Handihaler and mortality in COPD patients [1]. As COPD patients with moderate and severe cardiac or renal comorbidity were excluded from the TIOSPIR (Tiotropium Safety and Perfomance In Respimat) RCT, the jury is still out whether tiotropium Respimat is safe in COPD patients with comorbid cardiac or renal disease [2][3][4]. C.N.…”

“…During the last two decades, the increasingly demonstrated capacity of the usual gait speed to predict major health-related events in older persons [4] and its strong relationships with key pathophysiological mechanisms of ageing [5] have made this tool of particular interest in the clinical setting. It is now well established that gait speed should not be considered a mere measure of mobility, but indeed represents a more global marker of well-being.…”

New abilities of administration of tiotropium bromide using the aerosol delivery device Respimat®

“…В течение последних 3 лет ведутся бурные дискус сии, посвященные сердечно сосудистой безопас ности ТР [52][53][54][55][56]. В совокупном анализе 2 сходных по дизайну 1 годичных исследований E.Bateman et al показано, что число летальных исходов от любых причин среди больных, принимавших ТР, было не сколько выше: 2,4 и 2,7 % (при приеме 5 и 10 мкг ти отропия соответственно) по сравнению с пациента ми группы плацебо (1,6 %) [48].…”

From Handihaler to Respimat: tiotropium delivery systems

“…Опасение это было не гипотети ческим, а основанным на ряде публикаций, где при ведены достаточные доказательства для глобальной отмены ТР из за повышенного риска смерти у паци ентов с ХОБЛ [5,6]. В полемической статье, опубли кованной в Европейском респираторном журнале, также весьма категорично звучат опасения относи тельно безопасности применения ТР при ХОБЛ [7].…”

“…В 2008 г. был опубликован метаанализ 17 РКИ, на ос новании которого высказано мнение о необходимос ти осторожного применения ингаляционных М хо линоблокирующих средств в связи с риском смерти от сердечно сосудистой патологии, развития инфарк та миокарда и инсульта [5]. Однако при внедрении ТХ не появилось заключения о повышенной опасности его применения, а в последнем критическом метаана лизе [7] справедливо отмечено, что применение ТХ не увеличивает риска летального исхода при лечении больных ХОБЛ в сравнении с плацебо (относитель ный риск -ОР -0,92; 95% ный доверительный интервал -ДИ -0,80-1,05). Все это свидетельствует о том, что до появления устройства Респимат серьез ные нежелательные явления и риск смерти у боль ных ХОБЛ с сопутствующей сердечно сосудистой патологией не были причиной для отказа в примене нии этой группы препаратов в пульмонологии, в частности при ХОБЛ.…”