Abstract
Accurate and consistent determination of cause of death is challenging in chronic obstructive pulmonary disease (COPD) patients. TIOSPIR (N=17 135) compared the safety and efficacy of tiotropium Respimat 5/2.5 µg with HandiHaler 18 µg in COPD patients. All-cause mortality was a primary end-point. A mortality adjudication committee (MAC) assessed all deaths. We aimed to investigate causes of discordance in investigator-reported and MAC-adjudicated causes of death and their impact on results, especially cardiac and sudden death.
The MAC provided independent, blinded assessment of investigator-reported deaths (n=1302) and assigned underlying cause of death. Discordance between causes of death was assessed descriptively (shift tables).
There was agreement between investigator-reported and MAC-adjudicated deaths in 69.4% of cases at the system organ class level. Differences were mainly observed for cardiac deaths (16.4% investigator, 5.1% MAC) and deaths assigned to general disorders including sudden death (17.4% investigator, 24.6% MAC). Reasons for discrepancies included investigator attribution to the immediate (e.g. myocardial infarction (MI)) over the underlying cause of death (e.g. COPD) and insufficient information for a definitive cause.
Cause-specific mortality varies in COPD, depending on the method of assignment. Sudden death, witnessed and unwitnessed, is common in COPD and often attributed to MI without supporting evidence.
Abstract
Investigator-attributed causes of death may lead to unreliable estimates of cause-specific mortality in COPD http://ow.ly/uzt9308TePH
Footnotes
This article has supplementary material available from openres.ersjournals.com
Clinical trial: This study is registered at www.clinicaltrials.gov with identifier number NCT01126437.
Support statement: The TIOSPIR study was funded by Boehringer Ingelheim. Boehringer Ingelheim participated in the design of the study, the collection and analysis of the data, and preparation of the manuscript. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.com
- Received June 29, 2016.
- Accepted January 8, 2017.
- Copyright ©ERS 2017
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