COPD and Respiratory Health Spotlight: Page 2 of 2

June 17, 2013

Roflumilast Has Safe Cardiovascular Profile

Among patients with mild to moderate chronic obstructive pulmonary disease (COPD), the leading cause of morbidity and mortality is cardiovascular disease. Thus, evaluating the cardiovascular safety profile of new COPD medications is important, especially among older adults, who tend to have more comorbidities than younger patients. A recent study by William B. White, MD, Calhoun Cardiology Center, University of Connecticut School of Medicine, and associates sought to evaluate the cardiovascular safety of roflumilast compared with placebo. The results of their study were published in February in CHEST. In March 2011, roflumilast was approved by the FDA to decrease the frequency of flare-ups and prevent worsening of symptoms from severe COPD. White and colleagues pooled data from intermediate- and long-term placebo-controlled clinical trials of roflumilast in COPD. The studies comprised 12- to 52-week placebo-controlled trials that included more than 12,000 patients with moderate to very severe COPD (average age, 64 years). They assessed for major adverse cardiovascular events (MACE; ie, myocardial infarction, death, stroke). From more than 6500 patients taking roflumilast, 52 patients experienced a MACE (14.3 per 1000 patient-years), compared with 76 patients from the 5500 patients taking placebo (22.3 per 1000 patient-years); the MACE composite rate was significantly lower in the roflumilast group compared with the placebo group (hazard ratio vs placebo, 0.65; 95% confidence interval, 0.45-0.93; P=.019). “The implications of our study is that roflumilast was not found to have a cardiovascular safety concern,” said White in an interview with Annals of Long-Term Care: Clinical Care and Aging.® “The original studies compiled for this analysis were the typical safety and efficacy studies and not designed to determine or define a cardioprotective effect of roflumilast; hence, this study should not be considered evidence for a protective effect of this drug.” However, as patients with COPD have increased rates of cardiovascular morbidity and mortality, particularly when severely ill, “new agents for the treatment of COPD should have some evidence that they do not increase harm when approved for use in the United States,” White said.


Aclidinium Bromide Demonstrates Improvement in Static Lung Function and Exercise
Endurance in Patients With COPD

Aclidinium bromide is an anticholinergic indicated for the long-term treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. The FDA approved the agent in 2012 following three randomized clinical trials that demonstrated the drug’s safety and efficacy to improve airflow in COPD patients. New clinical evidence supporting the use of aclidinium bromide was presented during the 2013 American Thoracic Society International Conference. Two posters presented different patient outcomes gleaned from a double-blind, randomized, crossover study involving 112 patients with moderate to severe COPD (mean age, 60.3 years).

Kai Beeh, MD, Insaf Respiratory Institute, Wiesbaden, Germany, and colleagues evaluated the effects of aclidinium bromide on dynamic hyperinflation, exercise endurance time, and dyspnea (doi: 10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A2430). Patients were randomly assigned to receive aclidinium bromide 400 µg twice daily or placebo for 3 weeks. They performed constant-load exercise at a 75% peak incremental exercise work rate, with the primary end point being change in level of endurance from baseline to week 3. The results showed that at week 3, patients taking aclidinium bromide improved significantly in exercise endurance time (P=.021).

In the other study, Henrik Watz, MD, Pulmonary Research Institute, Hospital Grosshansdorf, Germany, and associates investigated the effects of aclidinium bromide therapy on improving static lung function and hyperinflation—two important therapeutic goals in COPD treatment (doi:10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A2431). The patients received either aclidinium bromide 400 µg twice daily or placebo for 3 weeks. The researchers measured trough inspiratory capacity (IC) and forced expiratory volume in 1 second trough and 2-hour post-dose functional residual capacity, residual volume, total lung capacity, and specific airway conductance. The results showed that compared with placebo, aclidinium bromide significantly increased adjusted mean trough IC and forced expiratory volume from baseline to week 3 (P=.02). The authors further concluded that these improvements in static lung function at 2 hours post-dose were significantly greater for aclidinium bromide than for placebo (all P<.001).