Differences in outcomes between GOLD groups in patients with COPD in the TIOSPIR^® trial

Abstract

Background

The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR^®, the largest randomized clinical trial in COPD performed to date.

Methods

A total of 17,135 patients from TIOSPIR^® were pooled and grouped by GOLD grading (A–D) according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular (CV) and respiratory mortality were assessed.

Results

Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV mortality – hazard ratio [HR] =1.74, P=0.004; all-cause mortality – HR =1.18, P=0.11). Group D patients had a higher incidence of all-cause mortality than Group B patients (10.9% vs 6.6%). Similar trends were observed regardless of respiratory or CV medication at baseline. In contrast, respiratory deaths increased consistently from Groups A–D (0.3%, 0.8%, 1.6%, and 4.2% of patients, respectively).

Conclusion

The data obtained from the TIOSPIR^® trial, supporting earlier studies, suggest that proportionally more CV medication and CV deaths occur in GOLD Group B COPD patients, although deaths attributed to respiratory causes are more prevalent in Groups C and D.

Keywords:

• TIOSPIR^®
• GOLD
• cardiovascular comorbidity
• mortality
• respiratory death
• cardiovascular death

Supplementary materials

Figure S1 Kaplan–Meier curves of patient events by GOLD Stage (I/II–IV).

Notes: (A) All-cause mortality, (B) respiratory deaths, (C) MACE deaths, and (D) hospitalizations (severe exacerbations).

Abbreviations: GOLD, Global Initiative for Chronic Obstructive Lung Disease; MACE, major adverse cardiovascular event.

Table S1 Number of patients with GOLD Stage I/II–IV at baseline by GOLD Group A–D at baseline

Table S2 Patient baseline characteristics by GOLD stage

Table S3 Type of baseline pulmonary and CV medication use categorized by GOLD stage

Table S4 CV outcomes and patient mortality by GOLD stage

Table S5 All-cause mortality by GOLD stage and by pulmonary and cardiac therapy at baseline

Acknowledgments

This study was funded by Boehringer Ingelheim. The authors wish to thank Achim Mueller, of Boehringer Ingelheim, for statistical support. Writing assistance was provided by Sarah J Petit of PAREXEL, funded by Boehringer Ingelheim.

Disclosure

Daniel Dusser reports receiving consulting fees, lecture fees, and payment for the development of educational activities from Boehringer Ingelheim, Pfizer, Novartis, Chiesi, Nycomed, and Dey Pharma. Robert Wise reports receiving consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Mylan, Novartis, Pfizer, Sunovion, Pulmonx, Spiration, Roche, Grifols, and AstraZeneca, and grant support from Boehringer Ingelheim, GlaxoSmithKline, Pearl Therapeutics, and Forest Laboratories. Ronald Dahl reports receiving consulting fees, lecture fees, and grant support from Boehringer Ingelheim and Novartis. Antonio Anzueto reports receiving consulting fees, lecture fees, and travel support from AstraZeneca, Boehringer Ingelheim, Forest Laboratories, GlaxoSmithKline, and Novartis, and grant support from GlaxoSmithKline. Kerstine Carter and Andy Fowler report being employees of Boehringer Ingelheim. Peter Calverley reports receiving consulting fees, lecture fees, and travel support from Novartis, GlaxoSmithKline, Boehringer Ingelheim, and Takeda. The authors report no other conflicts of interest in this work.