A groundbreaking study once challenged how we prevent heart attacks, suggesting a week of antibiotics could shield the heart for a year.
For decades, the battle against heart disease has focused on cholesterol, blood pressure, and smoking. But what if a common infection was also secretly damaging your arteries? This is the compelling and controversial theory that researchers explored in the South Thames Trial of Antibiotics in Myocardial Infarction and Unstable Angina (STAMINA), a study that proposed a surprising new weapon in the fight against heart disease: antibiotics.
The traditional view of coronary artery disease is one of gradual buildup. Fatty deposits, or plaques, made of cholesterol and other substances, accumulate in the walls of the arteries that supply blood to the heart. Over time, these plaques can harden or rupture, leading to blockages that cause chest pain (unstable angina) or full-blown heart attacks (acute myocardial infarction).
In the 1990s and early 2000s, a radical new idea began to gain traction. Scientists started finding evidence linking common chronic infections to this process. Two bacteria, in particular, came under suspicion:
A common cause of respiratory infections like bronchitis and pneumonia.
The primary cause of stomach ulcers.
Theory: Perhaps these bacteria, by setting up long-term, low-grade infections in the body, were fueling the inflammation that makes plaques unstable and prone to rupture. If true, this meant that eradicating these infections with a simple course of antibiotics could potentially reduce the risk of future cardiac events. The STAMINA trial was designed to put this exciting theory to the test 1 4 .
To determine whether fighting infection could protect the heart, researchers designed a meticulous clinical trial involving 325 patients who had been hospitalized with acute coronary syndromes—either a heart attack or unstable angina 1 4 .
Patients who had not taken antibiotics in the previous three months were eligible for the double-blind, placebo-controlled study.
Participants were randomly assigned to one of three groups, each receiving a different one-week course of treatment 1 4 :
Patients were then monitored for a full year. Researchers tracked specific markers of inflammation in the blood (like C-reactive protein and fibrinogen) and, most importantly, recorded any cardiac events, such as cardiac death or readmission to the hospital with an acute coronary syndrome 1 .
The trial used specific drug combinations to attack the suspected bacterial culprits. The table below breaks down this pharmaceutical toolkit.
| Medication | Function in the Trial | Specific Dosage |
|---|---|---|
| Azithromycin | A broad-spectrum antibiotic effective against Chlamydia pneumoniae. | 500 mg once daily 1 |
| Amoxicillin | A penicillin-type antibiotic effective against Helicobacter pylori. | 1000 mg twice daily 4 |
| Metronidazole | An antibiotic used in combination to eliminate Helicobacter pylori. | 400 mg twice daily 1 4 |
| Omeprazole | A proton-pump inhibitor that reduces stomach acid, helping antibiotics work better against H. pylori. | 20 mg twice daily 1 4 |
| Placebo | An inert substance given to the control group to provide a baseline for comparison. | N/A 4 |
Hospitalized with ACS
3 Groups
Cardiac Events & Inflammation Markers
When the results were analyzed, they were both significant and puzzling.
reduction in cardiac deaths and hospital readmissions at 12 weeks with antibiotic treatment
Placebo Group
Antibiotic Groups
The most dramatic finding was in clinical outcomes. At the 12-week mark, patients who had received either of the active antibiotic treatments had a 36% reduction in cardiac deaths and hospital readmissions compared to the placebo group. This benefit persisted throughout the entire year of follow-up. By the end of the study, a cardiac event had occurred in only 26% of patients in the antibiotic groups, compared to 39% in the placebo group 1 4 .
| Outcome Measure | Placebo Group | Antibiotic Groups (Combined) | Statistical Significance |
|---|---|---|---|
| Patients with a coronary event | 39% | 26% | Risk Ratio 0.6 (P=0.02) 4 |
| Reduction in adverse cardiac events | --- | 36% at 12 weeks | P=0.02 1 |
The data on inflammation markers was more mixed. Levels of C-reactive protein (CRP), a key inflammatory marker, were reduced in unstable angina patients receiving amoxicillin. Fibrinogen, another protein involved in inflammation and clotting, was reduced in both antibiotic groups, though the result was borderline for statistical significance 1 4 .
| Inflammatory Marker | Observed Effect | Patient Group | Statistical Significance |
|---|---|---|---|
| C-Reactive Protein (CRP) | Reduced levels | Unstable angina patients on Amoxicillin | P=0.03 1 |
| Fibrinogen | Reduced levels | Both antibiotic groups | P=0.06 1 |
The benefit of the antibiotics was completely independent of whether a patient was infected with H. pylori or C. pneumoniae 1 . In other words, patients who showed no signs of these infections were just as likely to benefit from the antibiotics as those who were infected.
The conclusion of the STAMINA trial was a head-scratcher. Antibiotic treatment significantly reduced adverse cardiac events, but the effect was independent of H. pylori or C. pneumoniae seropositivity 1 . How could this be explained?
The authors proposed several fascinating possibilities 4 :
The participants, from a relatively low socioeconomic area in England, might have had other undetected chronic infections (like bronchitis or periodontal disease) that also contribute to heart disease risk. The antibiotics could have inadvertently treated these.
The antibiotics themselves, particularly azithromycin, are known to have direct anti-inflammatory properties independent of their bacteria-killing abilities. This suggests the benefits might have come from calming the body's overall inflammatory state, not from eradicating a specific bug.
Despite its promising results, the STAMINA trial was not the final word. As an accompanying commentary noted, the study was relatively small, and its findings were not consistent with other, larger studies 4 . The hypothesis that targeted antibiotic therapy could prevent heart attacks was ultimately not widely adopted into clinical practice. Later, larger trials failed to replicate the dramatic benefits, and concerns about antibiotic resistance made long-term preventive use undesirable.
Nevertheless, the STAMINA trial left an indelible mark. It powerfully advanced the understanding of inflammation's central role in heart disease and opened up new avenues of research into the complex links between our body's infections, its immune response, and the health of our heart. It remains a classic example of how a surprising result in science can be just as valuable as a confirmed one, pushing medical knowledge forward in unexpected ways.