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Published on: August 30, 2018
Clarithromycin use and the risk of mortality and cardiovascular events: A systematic review and meta-analysis
Ching-Hui You1, Cheng-Kuan Lin2, Po-Hua Chen1
1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.
Insights
Clarithromycin (CLR) use does not increase long-term mortality or cardiovascular risks, even in patients with existing heart conditions. Further research is needed on short-term risks compared to other antibiotics.
Area of Science:
- Pharmacovigilance
- Cardiovascular Epidemiology
- Antibiotic Safety
Background:
- Macrolide antibiotics, including clarithromycin (CLR), have been linked to potential cardiovascular (CV) risks, but evidence specifically for CLR remains debated.
- Existing studies present conflicting data regarding the association between CLR use and adverse CV events and mortality.
Purpose of the Study:
- To conduct a comprehensive meta-analysis summarizing the association between clarithromycin use and the risks of all-cause mortality and major adverse cardiovascular events.
- To evaluate these risks based on follow-up duration (long-term, short-term, and immediate) and patient comorbidity status.
Main Methods:
- A systematic literature search was performed across major databases (PubMed, EMBASE, Web of Science, Cochrane Library) for relevant randomized controlled trials (RCTs) and observational studies published up to December 31st, 2018.
- Studies reporting all-cause mortality or CV adverse events using multivariate models were included. Pooled rate ratios (RRs) with 95% confidence intervals (CIs) were synthesized by study design and follow-up duration.
Main Results:
- The meta-analysis included 13 studies with over 8.3 million participants.
- No significant association was found between CLR use and increased long-term all-cause mortality (RR = 1.09, 95% CI = 0.91-1.32), irrespective of cardiovascular comorbidities.
- CLR use was not associated with increased risks of cardiac mortality (RR = 1.03, 95% CI = 0.53-2.01), acute myocardial infarction (RR = 1.29, 95% CI = 0.98-1.68), or arrhythmia (RR = 0.90, 95% CI = 0.62-1.32) compared to placebo.
Conclusions:
- Clarithromycin use is not significantly associated with increased long-term all-cause mortality, even in patients with cardiovascular disease comorbidities.
- Further randomized controlled trials are recommended to investigate the short-term cardiovascular risks of CLR compared to alternative antibiotics, especially in high-risk patient populations.
Background:
Although studies reported increased cardiovascular (CV) risks in patients treated with macrolides, the risks remain controversial among clarithromycin (CLR) users. We aimed to summarize the association between CLR use and the risks of mortality and CV events.
Methods:
We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies with population exposed to CLR published until December 31st, 2018. These studies reported either all-cause mortality (primary outcome) or CV adverse events (secondary outcomes) based on multivariate models. Effect measures were synthesized by study design and follow-up duration (long-term, ≥ 1 year; short-term, ≤ 3 months; and immediate, ≤ 2 weeks). This study has been registered on PROSPERO (ID: CRD42018089605).
Results:
This meta-analysis included 13 studies (3 RCTs and 10 observational studies) and 8,351,815 subjects (1,124,672 cases and 7,227,143 controls). Overall, CLR use was not associated with increased long-term all-cause mortality (pooled rate ratio RR = 1.09, 95% CI = 0.91-1.32), either among patients with or without comorbidities of cardiovascular diseases. Comparing CLR users to placebo, there is no additional risks of cardiac mortality (pooled RR = 1.03, 95% CI = 0.53-2.01), acute myocardial infarction (pooled RR = 1.29, 95% CI = 0.98-1.68), and arrhythmia (pooled RR = 0.90, 95% CI = 0.62-1.32).
Conclusions:
Our findings suggested no significant association between CLR use and subsequent long-term all-cause mortality, regardless having comorbidity of cardiovascular diseases or not. Further RCTs investigating the short-term CV risks of CLR use compared to alternative antibiotics are warranted, particularly in high-risk populations.
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