Tiotropium (Spiriva®) is almost universally prescribed for treatment of chronic obstructive pulmonary disease. It has been demonstrated to improve lung function (better spirometry, less air trapping) and health-related quality of life, and to reduce the frequency of exacerbations and hospitalizations in studies that compared use of tiotropium to placebo.
But can it save lives?
To date, several interventions in particular clinical settings in patients with COPD have been demonstrated to improve survival. These include; smoking cessation; use of supplemental oxygen in patients with persistent and profound hypoxaemia (low blood levels of oxygen); use of non-invasive ventilation in patients with ventilatory failure (high levels of carbon-dioxide in the blood; and even lung volume reduction in a very select group of patients. An analysis of data collected in the previously-published UPLIFT trial was released in the Blue Journal in mid-November, and suggests that tiotropium used regularly may be added to this list.
This was an interesting study. Two groups of patients (totaling 5993 patients) with COPD were randomized to receive either tiotropium or placebo. They were allowed to take any other inhalers except anticholinergics, and were even allowed to smoke (30% of them were smokers). Many patients discontinued the drug (44.6% in the placebo arm and 36.2% in the treatment arm) but continued in the study over its four year duration, and then a 30 day follow up period, during which tiotropium was stopped and ipratroprium (Atrovent ®) administered. .
During the 1440 days of the treatment period, 411 patients died while receiving placebo and 381 while receiving tiotropium (Hazards ratio (95% CI) 0.84 (0.73-0.97) p-0.016). If those in the two groups who discontinued treatment were included there was still a significant difference ( 491 vs 430, HR 0.87 (0.76-0.99), p-0.034). However, the follow-up period was a particularly bad one for those in the tiotropium group. During that period, 16 patients from the tiotropium group died, as opposed to only four from the placebo group. Six of those ‘tiotropium group’ deaths were patients who had remained on the medication right up until the end of the study – raising the question of whether withdrawal of the medication may have been harmful. By the end of the follow-up period, the survival difference was not statistically significant.
In a sub-group analysis it seemed as if smoking status at baseline might be a significant differentiator. Not too much was made of this in the discussion, but certainly for those patients still smoking there was no difference in risk of death between the two groups (medication vs placebo).
I think that the study design was a bit messy, including smokers and non-smokers and with a real hotch-potch of other inhalers in play. In this regard, however, it can certainly claim to be like real life. This recently-published new analysis of old data from the UPLIFT study gives us even more reason to prescribe tiotropium, and encourage our patients to remain on it.
But can it save lives?
To date, several interventions in particular clinical settings in patients with COPD have been demonstrated to improve survival. These include; smoking cessation; use of supplemental oxygen in patients with persistent and profound hypoxaemia (low blood levels of oxygen); use of non-invasive ventilation in patients with ventilatory failure (high levels of carbon-dioxide in the blood; and even lung volume reduction in a very select group of patients. An analysis of data collected in the previously-published UPLIFT trial was released in the Blue Journal in mid-November, and suggests that tiotropium used regularly may be added to this list.
This was an interesting study. Two groups of patients (totaling 5993 patients) with COPD were randomized to receive either tiotropium or placebo. They were allowed to take any other inhalers except anticholinergics, and were even allowed to smoke (30% of them were smokers). Many patients discontinued the drug (44.6% in the placebo arm and 36.2% in the treatment arm) but continued in the study over its four year duration, and then a 30 day follow up period, during which tiotropium was stopped and ipratroprium (Atrovent ®) administered. .
During the 1440 days of the treatment period, 411 patients died while receiving placebo and 381 while receiving tiotropium (Hazards ratio (95% CI) 0.84 (0.73-0.97) p-0.016). If those in the two groups who discontinued treatment were included there was still a significant difference ( 491 vs 430, HR 0.87 (0.76-0.99), p-0.034). However, the follow-up period was a particularly bad one for those in the tiotropium group. During that period, 16 patients from the tiotropium group died, as opposed to only four from the placebo group. Six of those ‘tiotropium group’ deaths were patients who had remained on the medication right up until the end of the study – raising the question of whether withdrawal of the medication may have been harmful. By the end of the follow-up period, the survival difference was not statistically significant.
In a sub-group analysis it seemed as if smoking status at baseline might be a significant differentiator. Not too much was made of this in the discussion, but certainly for those patients still smoking there was no difference in risk of death between the two groups (medication vs placebo).
I think that the study design was a bit messy, including smokers and non-smokers and with a real hotch-potch of other inhalers in play. In this regard, however, it can certainly claim to be like real life. This recently-published new analysis of old data from the UPLIFT study gives us even more reason to prescribe tiotropium, and encourage our patients to remain on it.
Andrew
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