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Managing Cardiovascular Risk of Macrolides: Systematic Review and Meta-Analysis
Angel Y S Wong1, Esther W Chan1, Shweta Anand1
1Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Introduction:
It was postulated that antibiotics including macrolides could be used for the secondary prevention of coronary heart disease but recent studies showed that macrolides increase the cardiovascular risk. We aimed to review the evidence of cardiovascular risk associated with macrolides regarding duration of effect and risk factors; and to explore the potential effect of statins for the prevention of cardiovascular events as a result of macrolide use.
Methods:
Several electronic databases (PubMed, EMBASE, Cochrane library) were searched to identify eligible studies. Observational studies and randomized controlled trials that investigated the association between macrolides and cardiovascular events in adults aged ≥18 years were included. A meta-analysis was conducted to investigate the short- and long-term risks of cardiovascular mortality, myocardial infarction, arrhythmia, and stroke. Methodological quality was assessed by the Newcastle-Ottawa scale and the Cochrane Collaboration's tool. The body of evidence was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines.
Results:
Observational studies were found to have a short-term risk of cardiovascular outcomes including cardiovascular mortality, myocardial infarction, and arrhythmia associated with macrolides but no risk was found in randomized controlled trials. However, no association for long-term risk (ranging from >30 days to >3 years) was observed in observational studies or randomized controlled trials.
Limitations:
The included studies reported different units of denominators for absolute risk and used different outcome definitions, which might increase the heterogeneity.
Conclusions:
More studies are required to investigate the short-term cardiovascular outcomes associated with different types of macrolides. Future studies are warranted to evaluate the effect of statins for preventing excess acute cardiovascular events associated with clarithromycin or other macrolides.
Insights
Macrolide antibiotics may increase short-term cardiovascular risk, particularly in observational studies, but not in randomized trials. Long-term risks were not identified, and statins may help prevent macrolide-associated events.
Area of Science:
- Cardiology
- Pharmacology
- Epidemiology
Background:
- Macrolides were considered for secondary prevention of coronary heart disease.
- Recent evidence suggests macrolides may elevate cardiovascular risk.
- This review examines macrolide-associated cardiovascular risks and potential statin interventions.
Purpose of the Study:
- To review evidence on cardiovascular risk from macrolides, considering duration and risk factors.
- To explore statins' potential role in preventing macrolide-induced cardiovascular events.
Main Methods:
- Meta-analysis of observational studies and randomized controlled trials.
- Searched PubMed, EMBASE, and Cochrane Library for studies on macrolides and cardiovascular events.
- Assessed risk of cardiovascular mortality, myocardial infarction, arrhythmia, and stroke.
Main Results:
- Observational studies indicated a short-term risk of cardiovascular outcomes with macrolides.
- Randomized controlled trials did not show an increased cardiovascular risk.
- No long-term cardiovascular risk (>30 days to >3 years) was found in either study type.
Conclusions:
- Further research is needed on short-term cardiovascular outcomes for specific macrolides.
- Future studies should evaluate statins for preventing acute cardiovascular events linked to macrolides like clarithromycin.
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