Long-term efficacy of tiotropium in relation to smoking status in the UPLIFT trial.
UPLIFT (Understanding Potential Long-Term Improvements in Function with Tiotropium), a 4-yr trial of tiotropium in chronic obstructive pulmonary disease, allowed for assessment of smoking status on long-term responses to maintenance bronchodilator therapy. 5,993 patients were randomised (tiotropium/placebo). Lung function, St George's Respiratory Questionnaire, exacerbations and adverse events were followed. Patients were characterised as continuing smokers (CS), continuing ex-smokers (CE), or intermittent smokers (IS) based on self-reporting smoking behaviour. 60%, 14% and 26% of patients were CE, CS and IS, respectively. The rate of forced expiratory volume in 1 s (FEV(1)) decline for placebo patients was most rapid in CS (-52+/-4, -37+/2 and -23+/2 mL.yr(-1) in CS, IS, and CE, respectively). Tiotropium did not alter FEV(1) decline, but was associated with significant improvements in pre- and post-bronchodilator FEV(1) over placebo that persisted throughout the 4-yr trial for each smoking status (pre-bronchodilator: 127, 55 and 97 mL at 48 months in CS, IS and CE, respectively; p< or =0.0003). Tiotropium reduced exacerbation risk in CS (HR (95% CI) 0.80 (0.67-0.95)), in CE (0.85 (0.79-0.92)) and trended towards significance in IS (0.89 (0.79-1.00)). At 4 yrs, St George's Respiratory Questionnaire for tiotropium patients improved the most in CS (-4.63 units, p = 0.0006) and the least in IS (-0.60 units, p = 0.51), [corrected] compared with control. Tiotropium provided long-term benefits irrespective of smoking status, although differences among categories were observed.
Tashkin
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Dept of Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1690, USA. DTashkin@mednet.ucla.edu
Celli
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Kesten
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Lystig
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Mehra
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Decramer
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D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use; D018680:Cholinergic Antagonists / Q000494:pharmacology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000628:therapy*; D011788:Quality of Life; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D012907:Smoking; D013997:Time Factors; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D010919:Placebos; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide