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Correspondence |

Cardiovascular Safety of RoflumilastRoflumilast FREE TO VIEW

Yuji Oba, MD; Nazir A. Lone, MD
Author and Funding Information

From the University of Missouri-Columbia.

Correspondence to: Yuji Oba, MD, University of Missouri-Columbia, 1 Hospital Dr, CE 412, Columbia, MO 65212; e-mail: obay@health.missouri.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(3):1082. doi:10.1378/chest.13-1036
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Published online
To the Editor:

In this issue of CHEST (see page 758), White et al1 report significantly lower major adverse cardiovascular events (MACEs) for roflumilast compared with placebo (hazard ratio, 0.65; 95% CI, 0.45-0.93; P = .019) from data in 12,054 patients with COPD. In addition to the studies analyzed not being designed or powered to examine cardiovascular outcomes, we would like to point out other limitations of the study.

First, the incidence of nonfatal stroke was the only component of MACEs that showed a statistically significant difference. It may not be appropriate to use a composite outcome if the magnitude of treatment effects is not comparable across the outcome components.2 It may be fair to say that roflumilast could decrease cerebrovascular events but not cardiovascular events or mortality because roflumilast was not associated with a lower incidence of such MACE components compared with placebo.

Second, the incidence of atrial fibrillation was not included in the study. Our recent meta-analysis showed that atrial fibrillation was significantly more frequent with roflumilast than with placebo (0.4% vs 0.2%; P = .02).3 The COPD safety pool White et al1 used included this information, and they should have incorporated it into the study.

Third, the discontinuation rate because of adverse effects was significantly more frequent with roflumilast than with placebo (15% vs 9.2%, P <.0001).3 The imbalance of dropout rates between the two groups may have affected the study results. The results may have been quite different if all patients recruited for roflumilast continued to take the drug during the entire study period. Outcomes could have been adjusted, using person-years of exposure as a denominator.

In conclusion, the study by White et al1 does not provide enough evidence to support the cardiovascular safety of roflumilast. More studies are needed to further investigate the cardiovascular safety of the drug.

References

White WB, Cooke GE, Kowey PR, et al. Cardiovascular safety in patients receiving roflumilast for the treatment of COPD. Chest. 2013;144(3):758-765.
 
Ferreira-González I, Busse JW, Heels-Ansdell D, et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ. 2007;334(7597):786. [CrossRef] [PubMed]
 
Oba Y, Lone NA. Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Ther Adv Respir Dis. 2013;7(1):13-24. [CrossRef] [PubMed]
 

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References

White WB, Cooke GE, Kowey PR, et al. Cardiovascular safety in patients receiving roflumilast for the treatment of COPD. Chest. 2013;144(3):758-765.
 
Ferreira-González I, Busse JW, Heels-Ansdell D, et al. Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials. BMJ. 2007;334(7597):786. [CrossRef] [PubMed]
 
Oba Y, Lone NA. Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Ther Adv Respir Dis. 2013;7(1):13-24. [CrossRef] [PubMed]
 
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