Inhaled steroids with and without regular salmeterol for asthma: serious adverse events

Area of Science:

• Respiratory Medicine
• Clinical Pharmacology
• Evidence-Based Medicine

Background:

• Epidemiological studies suggest a link between beta₂-agonist use and increased asthma mortality.
• Debate exists regarding the safety of regular long-acting beta₂-agonists (LABAs), especially when combined with inhaled corticosteroids (ICSs).

Purpose of the Study:

• To assess the risks of mortality and non-fatal serious adverse events (SAEs) in randomized controlled trials.
• To compare regular salmeterol and ICS treatment versus ICS alone in participants with chronic asthma.

Main Methods:

• Systematic review and meta-analysis of parallel-design randomized controlled trials.
• Inclusion of trials involving adults and/or children with asthma, randomized to regular salmeterol plus ICS versus ICS alone for at least 12 weeks.
• Data extraction on mortality and SAEs, including unpublished data from sponsors and regulatory submissions.

Main Results:

• No significant difference in all-cause mortality was observed between adults receiving salmeterol and ICS versus ICS alone (Peto OR 0.80, 95% CI 0.36 to 1.78).
• No significant difference in non-fatal serious adverse events (SAEs) of any cause was found for adults (Peto OR 1.14, 95% CI 0.97 to 1.33) or children (Peto OR 1.04, 95% CI 0.73 to 1.48).
• Asthma-related SAEs showed a potential increase in risk with salmeterol/ICS in adults (Peto OR 1.15, 95% CI 0.83 to 1.59) and children (Peto OR 1.25, 95% CI 0.72 to 2.16), though confidence intervals included no difference.

Conclusions:

• No difference in mortality or overall SAE risk was found between regular salmeterol/ICS and ICS alone in adults or children.
• The risk of asthma mortality remains uncertain but appears very low with both treatment strategies.
• Potential small increases in SAEs with salmeterol/ICS require balancing against clinical benefits, with adherence noted as a factor.