COPD’s month of danger

New use of inhaled long-acting beta, agonists or long-acting antimuscarinic antagonists was associated with a 1.5-fold increased cardiovascular risk within 30 days of initiation in patients with chronic obstructive pulmonary disease, irrespective of prior cardiovascular disease status and history  of exacerbations, according to a review of more than 280,000 COPD patients in Taiwan.

The relationship between cardiovascular disease (CVD) and LABAs and LAMAs in chronic obstructive pulmonary disease (COPD) has long been debated. The news study addressed some limitations of previous studies, which has found conflicting results ranging from no increased risk to up to a 4.5-fold increased risk of cardiovascular events when the medications were used for COPD.

Previous randomized trials haven’t raised much concern, but they included prior users who may have developed patients with baseline CVD. We cautioned physicians to closely monitor new users of LABAs and LAMAs for cardiovascular symptoms. Health care professionals should be vigilant for any cardiovascular symptoms during the first 30 days of inhalation therapy.

We suspect that there may exist a subgroup of patients with COPD who are particularly at risk of CVD with initial exposure to LABAs and LAMAs. We suggest that the use of inhaled long-acting bronchodilators in COPD needs to be performed before prescribing LABAs and LAMAs .

The team identified 284,220 COPD patients in the Taiwan National Health Insurance Research Database during 2007-2011 who were new to the medications. During a mean follow-up of two years, 37,719 developed severe CVD requiring hospitalization or emergency care, including coronary artery disease, heart failure, ischemic stroke, and arrhythmia.

The team compared their CVD subjects with controls who did not have a heart event and found the new LABA and LAMA use in COPD was associated with a 1.50-fold (95 percent confidence interval, 1.35-1.67; P less than .001) and a 1.52-fold (95 percent CI, 1.28-1.80; P less than .001) increased vascular risk within 30 days of initiation, respectively.

One severe CVD event requiring hospitalization or ED care occurred for every 406 (95 percent CI, 303-580) new LABA users and 391 (95 percent CI, 254-725) new LAMA users during the first 30 days of therapy.

The LABA and LAMA associated CVD risk remained significant, regardless of patient’s CVD history and COPD exacerbations. Analyses of individual CVD outcomes revealed increased risk of coronary artery disease and heart failure with LABA and LAMA treatment, and an increased risk for cardiac arrhythmias with LAMA therapy.

The cardiovascular risks peaked at around the 30th day of treatment, waned from 31-60 days of treatment, and reduced to a level lower than the baseline risk from 71 to 240 days.

Given that CVD is highly prevalent among patients with COPD, clinicians should also pay attention to the management of CVD risk factors throughout the duration of LABA or LAMA therapy… If needed, a preventive therapy for CVD should be considered during the initial treatment of inhaled long-acting bronchodilators.

LABAs and LAMAs are believed to cause sympathetic overactivation by activating sympathetic beta, adrenergic receptors and suppressing parasympathetic muscarinic-3 receptors, which could contribute to the CVD risk. Also LABA and LAMA use in COPD has been observed to increase inflammatory cytokine levels, which might also play a role.

The subjects were 40 years older, the mean age was 71.4 years and 68.9 percent of the participants were men.