Macrolide prescribing and preemptive electrocardiograms in asthma, COPD, ACO, and general population: a drug-utilization study

OBJECTIVE: Macrolides are used in patients with chronic respiratory conditions to prevent exacerbations. However, due to their QT interval prolonging effect, an electrocardiogram (ECG) assessment prior to long-term treatment is recommended. The objective was to evaluate the incidence of macrolides use (azithromycin, clarithromycin, erythromycin) in individuals with asthma, chronic obstructive pulmonary disease (COPD), asthma-COPD overlap (ACO), and to assess the frequency of ECGs performed prior to long-term macrolide prescribing. METHODS: We utilized data from the Dutch Integrated Primary Care Information (IPCI) database and Spanish Information System for Research in Primary Care (SIDIAP), between 2006 and 2022. The study population consisted of individuals diagnosed with asthma, COPD, and ACO with ≥365 days follow-up after diagnosis. Incidence was analyzed by type of macrolide, database, year, and prescribing-duration (short-, medium-, long-term [<30, 30-179, ≥180 days]). RESULTS: SIDIAP included 224,783 individuals with asthma, 167,524 with COPD, and 34,475 with ACO, while IPCI included 66,383 with asthma, 26,805 with COPD, and 7250 with ACO. The incidence of short-term use per 100,000 person-years (PYs) was 3500-6700 for azithromycin, 1300-2100 for clarithromycin and 200-300 for erythromycin. The incidence of medium- and long-term use was less than <1100/100,000 PYs. Incidence rates were higher in SIDIAP, females, and 60-79 year-olds. Medium- and long-term use was 2- to 4-fold higher in COPD and ACO than asthma, and increased over time. Database-registered ECGs were found in less than 1% of long-term macrolide users. CONCLUSIONS: Long-term macrolide users were on the rise among COPD- and ACO individuals; however, ECG monitoring was rare, raising concerns given guideline recommendations.