Pharmacotherapy. 2020 Jul 16. doi: 10.1002/phar.2445. Online ahead of print.
Hydroxychloroquine combined with azithromycin has been investigated for activity against COVID-19, but concerns about adverse cardiovascular effects have been raised. This study evaluated claims data to determine if risks for cardiovascular events were increased with hydroxychloroquine alone or combined with azithromycin. We identified data from 43,752 enrollees that qualified for analysis. The number of cardiovascular events increased by 25 (95% CI: 8, 42, p=0.005) per 1,000 people per year of treatment with hydroxychloroquine alone compared to pre-treatment levels and by 201 (95% CI: 145, 256, p<0.001) events per 1,000 people per year when individuals took hydroxychloroquine and azithromycin. These rates translate to an additional 0.34 (95% CI: 0.11, 0.58) cardiovascular events per 1,000 patients placed on a 5-day treatment with hydroxychloroquine monotherapy and 2.75 (95% CI: 1.99, 3.51) per 1,000 patients on a 5-day treatment with both hydroxychloroquine and azithromycin. The rate of adverse events increased with age following exposure to hydroxychloroquine alone and combined with azithromycin. For females aged 60-79 prescribed hydroxychloroquine, the rate of adverse cardiovascular events was 0.92 per 1,000 patients on 5 days of therapy, but it increased to 4.78 per 1,000 patients when azithromycin was added. The rate of adverse cardiovascular events did not differ significantly from zero for patients 60 years of age or younger. These data suggest that hydroxychloroquine with or without azithromycin is likely safe in individuals under 60 years of age if they do not have additional cardiovascular risks. However, the combination of hydroxychloroquine and azithromycin should be used with extreme caution in older patients.