Chest
Original ResearchCOPDFeaturedCardiovascular Safety in Patients Receiving Roflumilast for the Treatment of COPD
Section snippets
Clinical Studies and Protocol
The prespecified approach by charter was to determine the incidence of MACE as previously defined9 (nonfatal MI, nonfatal stroke, and cardiovascular death) for roflumilast and placebo (or a combination of roflumilast and active agent vs placebo and active agent). All COPD clinical studies from the roflumilast drug safety database that met the following criteria were included in the analysis: (1) randomized trials with a parallel group design, (2) one treatment arm of roflumilast ≥ 250 μg per
Baseline Characteristics of the Treatment Groups
As shown in Table 2, 12,054 patients were included in the analysis; 6,563 patients were randomized to roflumilast 250 to 500 μg total daily dose, and 5,491 were randomized to placebo. Baseline patient characteristics in the comparisons between roflumilast and placebo were similar for age, sex, COPD severity, and concomitant cardiovascular and pulmonary medications. Similar proportions of the patients in the roflumilast and placebo treatment groups had cardiovascular risk factors of
Discussion
In an analysis of clinical trials involving > 12,000 patients, reductions in MACEs (nonfatal MI, nonfatal stroke, and cardiovascular death) were found in patients treated with the PDE-4 inhibitor roflumilast compared with patients who received placebo. Of note, subgroup analyses indicated that the risk reduction might be more prominent in patients with severe vs moderate COPD. Changes in MACEs for roflumilast relative to placebo were not altered substantially as a result of baseline
Conclusions
This cardiovascular safety analysis of data from randomized controlled trials of roflumilast in patients with COPD for up to 1 year demonstrates a lower incidence of cardiovascular events in those treated with roflumilast vs placebo. Further resolution of the absolute and relative cardiovascular effects of systemic PDE-4 inhibition will require purposefully designed prospective randomized trials of appropriate durations.
Acknowledgments
Author contributions: Dr White had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Dr White: contributed as principal investigator and chair of the cardiovascular adjudication committee to the conception and design of the analysis and drafting of the manuscript.
Dr Cooke: contributed as a member of the cardiovascular adjudication committee to the data interpretation and critical review of the manuscript.
Dr
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Funding/Support: Funding was provided by Research and Development, Forest Research Institute Inc, a wholly owned subsidiary of Forest Laboratories, Inc, Jersey City, NJ, and Nycomed: a Takeda Company, Zurich, Switzerland.
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