SESSION TITLE: COPD Exacerbation Risk
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Wednesday, October 29, 2014 at 02:45 PM - 04:15 PM
PURPOSE: To examine seasonal variations in mortality and exacerbations in COPD patients in the TIOtropium Safety and Performance In Respimat® (TIOSPIR®) trial (NCT01126437).
METHODS: TIOSPIR was a large, multinational, randomized, double-blind, double-dummy, event-driven, parallel-group trial in COPD patients age ≥40 years, smoking history ≥10 pack-years, post-bronchodilator FEV1 ≤70% and FEV1/FVC ≤0.70. Patients with a respiratory infection/COPD exacerbation within 4 weeks before randomization were excluded. Inclusion/exclusion criteria allowed study of a broad COPD population. Maintenance therapy, except inhaled anticholinergics, was allowed. Patients were randomized to tiotropium Respimat® 2.5 or 5 μg qd or tiotropium HandiHaler® 18 μg qd. Primary outcomes were times to death (all-cause) and first exacerbation; secondary outcomes included: total exacerbations and those leading to hospitalization. Death rates were calculated from the vital status set (VSS; full follow-up period) and exacerbation rates from the treated set (TS; on-treatment period), taking into account time at risk and treatment duration, respectively. Southern hemisphere (SH) data were shifted by 6 months to compare with northern hemisphere (NH) data; eg, winter: Jun-Aug (SH) and Dec-Feb (NH). Data were pooled since mortality and exacerbations did not differ significantly between treatments.
RESULTS: 17,182 patients were randomized and 17,135 received ≥1 dose of tiotropium at >1200 sites in 43 NH (VSS: n=15,987; TS: n=15,968) and 7 SH (VSS/TS: n=1148) countries (recruitment: May 2010-Apr 2011; study end: May 2013). Overall, death rates were highest in winter (peak 3.38/1000 patient-months) and lowest in the first fall and mid-summer months (2.24 and 2.25, respectively). Overall, first exacerbation rates were highest in winter (peak 25.7) vs summer (lowest 12.2) as were total exacerbation rates (peak 58.9 vs lowest 31.3). First and total exacerbation rates leading to hospitalization were highest in the last winter month (8.64 and 12.6) and lowest in the last summer month (3.37 and 5.50), respectively. NH and SH data examined separately had similar seasonality profiles.
CONCLUSIONS: Overall, in COPD patients, rates of death, exacerbations and exacerbations leading to hospitalization were greatest in winter and lowest in summer.
CLINICAL IMPLICATIONS: The data suggest clinical trials of COPD exacerbation reduction should be conducted in winter and patients and healthcare workers should be educated to increased awareness of these events.
DISCLOSURE: Robert Wise: Grant monies (from industry related sources): GSK, BIPI, Merck, Pearl, Consultant fee, speaker bureau, advisory committee, etc.: GSK, BIPI, Mylan, Spiration, Sunovion, Pulmonx, Intermune, Merck, Janssen, Medimune, AZ, Novartis, Genentech Peter Calverley: Consultant fee, speaker bureau, advisory committee, etc.: GSK, BI, Nycomed, Novartis, Forest, AZ, Takeda Nycomed Kerstine Carter-Scherer: Employee: BI Emmanuelle Clerisme-Beaty: Employee: BI Norbert Metzdorf: Employee: BI Antonio Anzueto: Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca, Boehringer Ingelheim, Forest Laboratories, GlaxoSmithKline, and Novartis, Grant monies (from industry related sources): Forest, GSK
No Product/Research Disclosure Information