A five-day course of azithromycin carried a 2.49-fold higher risk of cardiovascular death than amoxicillin, i.e. 47 extra deaths per million courses, and 245 per million in high-risk patients.
Original statement
أظهر Ray في NEJM عام 2012 أن دورة من خمسة أيام من الأزيثرومايسين ترفع خطر الوفاة القلبية الوعائية بمعدل 2.49 مقارنة بالأموكسيسيلين
verbatim according to source. Translation by the project; the Arabic wording is authoritative.
Translation
A five-day course of azithromycin carried a 2.49-fold higher risk of cardiovascular death than amoxicillin, i.e. 47 extra deaths per million courses, and 245 per million in high-risk patients.
Origin
- Source status
- Archive editors
- Attribution
- Archive editors (eltayebat.com)
- Origin
- https://eltayebat.com/rule/antibiotic-overuse/
- Attribution uncertainty
- Archive editorial narrative and featured-study cards, written by the archive operators; study selection is the archive's, not necessarily Elawady's.
- Claimed mechanism
QT prolongation/arrhythmia.
- Claimed health effect
Cardiovascular death.
- Population concerned
Adults (Tennessee Medicaid)
- Geographic restriction by Elawady
none found
Scientific assessment
Mostly true – Correct at its core, but with limitations or minor inaccuracies.
Certainty of evidence: low – Further research is likely to change the assessment considerably.
1. What was claimed?
Azithromycin cardiac risk.
2. What is demonstrably correct?
HR 2.49 (1.38-4.50) vs amoxicillin; 47 additional CV deaths per million courses; 245 per million in the highest risk decile (A-ABX-13). The archive also reports the absolute numbers, which is good practice.
3. What is wrong or exaggerated?
Nothing misreported. It is a drug-specific risk, not evidence that antibiotics in general are dangerous.
4. What remains unclear?
How far the result applies to lower-risk populations: a Danish study of adults aged 18-64 found no excess (I-ABX-120).
5. Which studies support it?
6. Which studies contradict it?
Limiting: in 1.1 million azithromycin courses in Danish adults aged 18-64, cardiovascular death was not increased compared with penicillin V (RR 0.93, 0.56-1.55; risk difference -1 per million, -9 to 11) (I-ABX-120). A meta-analysis of 33 studies found no association of macrolides with cardiovascular mortality, but a small increase in myocardial infarction (OR 1.15, 1.01-1.30) (I-ABX-121).
7. What applies to Germany and Europe?
A Danish nationwide study found no excess cardiovascular death with azithromycin compared with penicillin V in adults aged 18-64 (I-ABX-120).
8. What is known about Egypt?
No Egyptian data were reviewed.
9. What practical conclusion is appropriate?
Drug choice matters in patients with heart risk.
Assessment details
- Rationale for certainty of evidence
Numbers correctly reported from a large observational cohort; single study read; absolute risk is small; residual confounding possible.
- Source quality
High-quality pharmacoepidemiology (NEJM).
- Regional transferability
Moderate.
- Individual exceptions
Higher-risk patients have higher absolute risk.
- Regional scope of the claim
- not specified
- Last reviewed
- 26 October 2026 provisional
Scientific evidence in detail
True only under certain conditions – The claim holds only for certain doses, groups of people, preparations or circumstances.
Research question: Does a 5-day azithromycin course increase cardiovascular death compared with amoxicillin, and by how much in absolute terms?
Research question in detail (PECO)
- Population
- Adults
- Intervention or exposure
- Azithromycin
- Comparison
- Amoxicillin / penicillin V / no antibiotic
- Geographic scope
- Population-dependent (baseline cardiac risk)
- Outcomes
- Cardiovascular death
Study results as reported by the authors. Our assessment follows below.
What speaks for the claim?
Azithromycin and heart deaths
Ray WA et al.. N Engl J Med 2012 · PMID 22591294 · DOI 10.1056/NEJMoa1003833 Cohort studyfull text, structured risk-of-bias assessmentTennessee Medicaid cohort (NEJM 2012).
- Actual result
- HR 2.49 (1.38-4.50) vs amoxicillin; +47 CV deaths per million courses; +245 in highest-risk decile.
- Methodological quality
- moderate-high
- Relevance
- direct: source of claim
- Limitations
- Medicaid population with higher baseline risk.
What speaks against the claim?
Danish study: azithromycin not linked to heart deaths in younger adults
Svanström H et al.. N Engl J Med 2013 · PMID 23635050 · DOI 10.1056/NEJMoa1300799 Cohort studyabstract checkednewly addedDanish nationwide cohort, adults 18-64.
- Actual result
- RR 0.93 (0.56-1.55) vs penicillin V; risk difference -1 (-9 to 11) per million.
- Methodological quality
- high
- Relevance
- direct (lower-risk population)
- Limitations
- Younger population.
Pooled studies: macrolides not linked to cardiac death overall
Gorelik E et al.. Antimicrob Agents Chemother 2018 · PMID 29610207 · DOI 10.1128/AAC.00438-18 Meta-analysisabstract checkednewly addedMeta-analysis of 33 studies (22.6 million subjects).
- Actual result
- No association of macrolides with CV mortality; MI OR 1.15 (1.01-1.30).
- Methodological quality
- moderate
- Relevance
- direct
- Limitations
- Observational inputs.
What does the overall evidence say?
Editorial assessment based on the studies above – not itself a study result.
Which position is better supported?
The archive reproduces the Ray study's numbers correctly, including absolute risks. The excess risk was not replicated in younger general-population adults, and pooled data show no class-wide increase in cardiovascular death; the risk appears limited to patients with high baseline cardiac risk.
Why some studies weigh more
Active-comparator cohorts weigh most; the Danish study excludes an excess as large as +47 per million in young and middle-aged adults.
Is a causal relationship established? Possible, not established QT prolongation is a recognised mechanism; magnitude depends on baseline risk.
Remaining uncertainty
Risk in elderly cardiac patients.
Justified conclusion
Correctly reported single-study result; should be read as a risk mainly for high-risk patients.
Why do studies seem to disagree?
Ray (older, sicker Medicaid population) vs Svanström (healthy Danish adults 18-64): different baseline risk, not a contradiction of the high-risk finding.
Does this depend on the country?
- General biological effects
- Drug pharmacology universal; absolute risk depends on cardiac risk profile.
- Eating habits
- Not applicable (medicine use, not diet).
- Legal rules
- Not applicable.
- Actual monitoring data
- Not applicable.
A regional difference that changes the conclusion is not supported by robust data.
Statistical re-check
- CI symmetry and absolute risk – RR 0.93 (0.56-1.55) symmetric; crude rate ratio 0.73; NNH for Ray about 21,000 courses (4,100 in highest-risk decile). recalculated
Certainty of the overall evidence (GRADE, simplified)
- Main outcome
- Cardiovascular death after azithromycin
- Starting level
- low (observational studies)
- Reasons for downgrading
- inconsistency between populations
- Result
- low
Simplified assessment by a single reviewer, following the GRADE approach; not a formal GRADE panel. GRADE rates the body of evidence for one outcome, not individual studies.
Search strategy
Documented literature searches for this review (search strings in the original database syntax).
| Database | Date | Search | Looking for | Hits | Included |
|---|---|---|---|---|---|
| Europe PMC | 26 October 2026 | TITLE:"Use of azithromycin and death from cardiovascular causes" | contradicting evidence | 1 | |
| Europe PMC | 26 October 2026 | TITLE:(azithromycin OR macrolide*) AND TITLE:(cardiovascular OR cardiac OR arrhythmia OR "sudden death") AND (PUB_TYPE:"Systematic Review" OR TITLE:"meta-analysis" OR TITLE:"cohort") | both directions | 13 |
Open questions
Risk in elderly patients with cardiac disease outside the US.
How deeply was this checked?
3 linked studies: 1 checked in full text (1 of them with a structured risk-of-bias assessment), 2 on the basis of the abstract, 0 bibliographically only. No formal assessment with two independent reviewers and no independent human expert review has taken place yet.
Last scientific review: 26 October 2026
History of the verdict
- 25 October 2026 · Phase 1 · Initial assessment: Mostly true (low)
- 26 October 2026 · Phase 4 (systematic evidence review) · Re-examined with extended evidence; verdict unchanged: Mostly true (low)
Numbers are correctly reported; replication data limit generalisation to high-risk patients, which is reflected in the wording, not in the verdict.
New sources: I-ABX-120 I-ABX-121
In plain language
A large US study found that azithromycin was linked to a small extra risk of death from heart problems compared with amoxicillin: about 47 extra deaths per million treatment courses. In people with high heart risk it was about 245 per million. This is a known drug-specific risk that doctors consider when choosing an antibiotic.
Studies on this claim
Studies supporting the claim (1)
-
Azithromycin and heart deaths
Ray WA et al.. N Engl J Med 2012 · PMID 22591294 · DOI 10.1056/NEJMoa1003833Cohort studycited by the Tayebat archivefull text, structured risk-of-bias assessment★ key studyAzithromycin was linked to about 47 extra heart deaths per million courses compared with amoxicillin.
Does the study support the specific claim? Yes · Methodological quality: high · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Test CV risk.
- How was the study done?
Cohort.
- How many people, animals or samples were studied?
347,795 azithromycin courses vs 1.39 million matched non-use periods and 1.35 million amoxicillin courses (Tennessee Medicaid, 1992-2006).
- What was actually found?
CV deaths during 5 days: 85.2 per million azithromycin courses vs 31.5 per million amoxicillin courses; HR 2.49 (1.38-4.50) vs amoxicillin.
- How large was the observed effect?
HR 2.49; +47/million.
- What do the results mean in everyday life?
Rare but real for high-risk patients.
- What are the study's limitations?
Observational; few deaths (29); Medicaid population; no difference from levofloxacin.
- What does it say about Elawady's specific claim?
Supports.
- Do the results apply to Germany and Europe?
Moderate.
- What can explicitly not be concluded from this study?
That antibiotics are generally dangerous.
No study in this group is marked as key.
Studies contradicting or limiting the claim (2)
-
Danish study: azithromycin not linked to heart deaths in younger adults
Svanström H et al.. N Engl J Med 2013 · PMID 23635050 · DOI 10.1056/NEJMoa1300799Cohort studyindependent cross-checkabstract checked★ key studyCompared with penicillin, azithromycin showed no extra cardiovascular deaths in Danish adults aged 18-64.
No excess CV death vs penicillin V in Danish adults 18-64 (RR 0.93)
Does the study support the specific claim? No · Methodological quality: high · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
Study explained simply
- What did the researchers want to find out?
Check azithromycin heart risk in the general population
- How was the study done?
National cohort
- How many people, animals or samples were studied?
Over 1 million azithromycin courses
- What was actually found?
No increase vs penicillin V
- How large was the observed effect?
RR 0.93 (0.56-1.55)
- What do the results mean in everyday life?
For most younger adults the risk is not measurable
- What are the study's limitations?
Few events; younger population
- What does it say about Elawady's specific claim?
Limits the claim to higher-risk groups
- Do the results apply to Germany and Europe?
High
- What can explicitly not be concluded from this study?
Risk in older heart patients
-
Pooled studies: macrolides not linked to cardiac death overall
Gorelik E et al.. Antimicrob Agents Chemother 2018 · PMID 29610207 · DOI 10.1128/AAC.00438-18Meta-analysisindependent cross-checkabstract checkedAcross 33 studies, macrolides were not linked to cardiovascular death; a small MI signal was found.
No pooled association with CV mortality; small MI signal
Does the study support the specific claim? No · Methodological quality: moderate · Certainty of evidence: see overall assessment of the claim
Original publication · Scientific details
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
No study in this group is marked as key.
Studies with mixed or unclear results (0)
No studies in this group.
Regional context
Germany / EU
A Danish nationwide study found no excess cardiovascular death with azithromycin compared with penicillin V in adults aged 18-64 (I-ABX-120).
Egypt
No Egyptian data were reviewed.
What applies in my country?
General scientific assessment
Mostly true Correctly reported; a small, drug-specific risk mainly in high-risk patients, not replicated in younger general-population adults.
This statement concerns biological or medical relationships. The scientific assessment above applies regardless of the country; country-specific food data do not change it.
References
- Azithromycin and the risk of cardiovascular death.. Ray WA et al.. N Engl J Med 2012 · PMID 22591294 · DOI 10.1056/NEJMoa1003833
- Use of azithromycin and death from cardiovascular causes.. Svanström H et al.. N Engl J Med 2013 · PMID 23635050 · DOI 10.1056/NEJMoa1300799
- Systematic Review, Meta-analysis, and Network Meta-analysis of the Cardiovascular Safety of Macrolides.. Gorelik E et al.. Antimicrob Agents Chemother 2018 · PMID 29610207 · DOI 10.1128/AAC.00438-18