AUTHOR=Yu Ben-Hui , Chen Yen-Chun , Li Yi-Da , Chiou Wen-Yen , Chen Yi-Chun 

TITLE=No dose-response relationship of clarithromycin utilization on cardiovascular outcomes in patients with stable coronary heart disease: Analysis of Taiwan’s national health insurance claims data

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1018194

DOI=10.3389/fcvm.2022.1018194

ISSN=2297-055X

ABSTRACT=Background: It has been reported that clarithromycin has a potential for adverse cardiovascular outcomes. However, the dose-response relationship of clarithromycin with cardiovascular outcomes in patients with stable coronary heart disease (CHD) remains uncertain.
Methods: This cohort study retrospectively analyzed a national health insurance claims data from Taiwan’s 2005 Longitudinal Generation Tracking Database. We used a new-user design and 1:1 propensity score matching. A total of 9631 eligible clarithromycin users and 9631 nonusers in 2004-2015 were subject to final analysis. All patients were followed-up after receiving clarithromycin or on the matched corresponding date until occurrence of cardiovascular morbidity in the presence of competing mortality, all-cause and cause-specific mortality, or through the end of 2015. The effect of cumulative dose and exposure duration of clarithromycin on cardiovascular outcomes were also addressed.
Results: Clarithromycin use, compared with nonuse, was associated with higher risk for all-cause (adjusted hazard ratios [aHR], 1.43; 95% confidence interval, 1.29-1.58), cardiovascular (1.35; 1.09-1.67), and noncardiovascular (1.45; 1.29-1.63) mortality, but not for overall cardiovascular morbidity. Further analysis of individual cardiovascular morbidity demonstrated major risk for heart events (1.25; 1.04-1.51) in clarithromycin users than nonusers. However, there was no relationship of cumulative dose and exposure duration of clarithromycin on cardiovascular outcomes. Analyses of the effects over time showed that clarithromycin increased cardiovascular morbidity (1.21; 1.01-1.45), especially heart events (1.39; 1.10-1.45), all-cause (1.57; 1.38-1.80), cardiovascular (1.58; 1.20-2.08), and noncardiovascular (1.57; 1.35-1.83) mortality during the first three years. Thereafter, clarithromycin effect on all outcomes almost dissipated. 
Conclusion: Clarithromycin use was associated with increased risk for short-term cardiovascular morbidity (especially, heart events) and mortality without a dose-response relationship in patients with stable CHD. Hence, patients with stable CHD while receiving clarithromycin should watch for these short-term potential risks.