Meta-analysisindependent cross-checkabstract checked I-ABX-121 standard review
Pooled studies: macrolides not linked to cardiac death overall
Systematic Review, Meta-analysis, and Network Meta-analysis of the Cardiovascular Safety of Macrolides.
Overview
Gorelik E et al.. Antimicrob Agents Chemother 2018 · PMID 29610207 · DOI 10.1128/AAC.00438-18
Across 33 studies, macrolides were not linked to cardiovascular death; a small MI signal was found.
Does the study support the specific claim? No · Methodological quality: moderate
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Pool macrolide heart-safety data
- How was the study done?
Meta-analysis
- How many people, animals or samples were studied?
33 studies
- What was actually found?
No link with CV death; small MI increase
- How large was the observed effect?
MI OR 1.15
- What do the results mean in everyday life?
The heart risk is small and drug-dependent
- What are the study's limitations?
Observational data
- What does it say about Elawady's specific claim?
Limits the claim's generality
- Do the results apply to Germany and Europe?
High
- What can explicitly not be concluded from this study?
Risk in specific high-risk groups
Scientific in-depth review
1. Full reference
- Authors
- Gorelik E et al.
- Journal
- Antimicrob Agents Chemother
- Year
- 2018
- Identifier
- PMID 29610207 DOI 10.1128/AAC.00438-18
- Verification
- verified – PubMed efetch 2026-10-26 + Crossref
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Not stated in abstract.
2. Research question
Are macrolides associated with arrhythmia, cardiovascular death or myocardial infarction?
3. Study design and population
- Study design
- Meta-analysis – Systematic review, meta-analysis and network meta-analysis
- Population
Subjects exposed to macrolides
- Country
Multinational
- Period
Searches to February 2018
- Sample size
33 studies, 22,601,032 subjects
- Inclusion and exclusion criteria
Studies reporting CV outcomes with macrolides
4. Methods and endpoints
- Exposure / intervention
Macrolides (azithromycin, clarithromycin, erythromycin)
- Comparator
Non-use or other antibiotics
- Endpoints
Arrhythmia, CV death, MI
- Statistical methods
Random-effects ORs; network MA
5. Actual results
- Results
Macrolide use not associated with arrhythmia or cardiovascular mortality; MI OR 1.15 (95% CI 1.01-1.30); erythromycin and clarithromycin associated with higher MI risk than azithromycin (OR 1.58 and 1.41).
- Absolute risks
not reported
- Authors' conclusion
Macrolides as a group are associated with MI but not with arrhythmia or cardiovascular mortality; residual confounding possible.
6. Strengths
- Very large pooled data
- Drug comparisons
7. Weaknesses
- Observational inputs
- Heterogeneous designs
8. Risk of bias
- Orienting tool
- AMSTAR 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- some concerns
- Rationale
Mixed designs pooled.
9. Assessment of the statistical interpretation
Pooled null for CV death contrasts with Ray.
10. Relevance to the specific claim
Pooled evidence does not confirm an excess CV death risk for macrolides as a class.
11. Independent contrary findings
Pooling may dilute high-risk subgroup effects.
12. Transferability to Germany and Europe
High.
13. Overall methodological judgement
Weakens generalisation of the 2.49-fold estimate.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | moderate |
| Risk of bias | some concerns |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | mixed |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
High-risk subgroups.