Secondary antibiotic prophylaxis reduces progression of rheumatic heart disease in children
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In children and adolescents with latent rheumatic heart disease, secondary antibiotic prophylaxis was associated with lower risk for disease progression at 2 years, researchers reported at the American Heart Association Scientific Sessions.
For the GOAL trial, Andrea Beaton, MD, pediatric cardiologist and associate professor of pediatrics at Cincinnati Children’s Hospital, and colleagues randomly assigned 916 patients aged 5 to 17 years in northern Uganda with confirmed latent rheumatic heart disease to receive prophylaxis via injections of penicillin G benzathine every 4 weeks for 2 years or no prophylaxis.
All patients underwent echocardiography at baseline and at 2 years, and 799 had results available for the final analysis. The primary outcome was progression of latent rheumatic heart disease at 2 years as determined by echocardiography. The results were simultaneously published in The New England Journal of Medicine.
“We have known for almost a decade that we can find rheumatic heart disease earlier through echo screening,” Beaton said during a presentation. “Using echo to screen apparently healthy populations has shown about 1.3% of children in rheumatic heart disease-endemic areas could potentially benefit from secondary antibiotic prophylaxis. However, not knowing if children with the earliest form of this disease will benefit has stalled progress of echo screening.”
Compared with controls, the prophylaxis group had lower rates of progression of latent rheumatic heart disease at 2 years (0.8% vs. 8.2%; risk difference, –7.5 percentage points; 95% CI, –10.2 to –4.7; risk ratio = 0.09; 95% CI, 0.03-0.29; P < .001), Beaton said.
The number needed to treat with prophylaxis in order to prevent one progression of rheumatic heart disease was 13 (95% CI, 10-21), according to the researchers.
Regression of latent rheumatic heart disease at 2 years occurred in 48.9% of the prophylaxis group compared with 47.8% of the control group (risk difference, 1.5 percentage points, 95% CI, –5.4 to 8.4), and among all participants with regression, 94% had a normal echocardiogram at 2 years, according to the results.
Two patients had prophylaxis-related serious adverse events, including one incidence of mild anaphylactic reaction, reflecting less than 0.1% of doses of the prophylactic regimen, according to the researchers.
In the prophylaxis group, mean age was 12.6 years and 43% were male. In the control group, mean age was 12.5 years and 46% were male.
“From these data, we can say that secondary antibiotic prophylaxis results in a significant and substantial reduction in rheumatic heart disease progression in children with latent rheumatic heart disease,” Beaton said. “We don’t have sufficient justification yet for widespread screening, as we need to translate these data into real-world application, look at barriers to secondary prophylaxis in the community, look into health system strengthening for echo screening integrated into public health systems and shore up BPG supply chains. Also, half of children regressed, most to normal, with or without prophylaxis, so we need better risk stratification.”
Beaton said the researchers have received funding to conduct the GOAL Post study, a longer-term follow-up of the GOAL cohort.
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Sandeep Krishnan, MD, FACC, FSCAI, RPVI
This is a fascinating question to ask. Although there is not a lot of rheumatic heart disease in the United States, it is quite common in the rest of the world, especially in countries with lower socioeconomic status, and results in many deaths annually. It’s important if we can figure out, as the adage goes, if an ounce of prevention is worth a pound of cure. In this case, if we can prevent patients from developing true valvular heart disease in childhood to the point where they need surgery, we can do something good.
The absolute risk reduction and the relative risk reduction were monumental. The number needed to treat of 13 is very powerful. Also of note is that this is a low-cost intervention, because we are giving a generic medication once per month for 2 years.
The question is how are these patients going to be found in the real world. That may be a higher-cost intervention because it may require screening echocardiography. Unfortunately, a lot of patients develop rheumatic heart disease because they did not have access to health care to begin with. They may not have had access to antibiotics in a timely manner. They may have thought they had strep throat which would go away on its own, after which they get rheumatic fever which may not be diagnosed, and then years later they have mitral valve stenosis and cannot walk more than 10 feet. By the time they present with end-stage valvular disease, it is too late and surgery is required. So proving that a screening program works is very exciting.
The American College of Cardiology is well-suited to help implement programs like this through its international chapters and contacts. But there is relevance in the U.S. as well. A paper published in August (de Loizaga SR, et al. J Am Heart Assoc. 2021;doi:10.1161/JAHA.120.020992) found that in 22 U.S. pediatric institutions from 2008 to 2018, there were 947 children between ages 4 and 17 years with acute rheumatic fever or rheumatic heart disease. That is a significant amount, and we have the opportunity to include the regimen from GOAL as part of guideline-directed medical therapy for these patients. While it would be an off-label use, this is a medication that has been around a long time and has a good side-effect profile. More research should be conducted in this arena and longer-term follow up should be continued. The authors should be commended on their work.
A paradox is that we have an overuse of antibiotics in this country, but we still see rheumatic heart disease, and that will continue with immigration from populations at higher risk for rheumatic heart disease, and with children born in the U.S. who live below the poverty line and have poor access to health care. This is a reason why we need to ensure that everyone has good access to health care.
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Beaton A, et al. Helen B. Taussig Memorial Lecture and Outstanding Research Awards in Pediatric Cardiology. Presented at: American Heart Association Scientific Sessions; Nov. 13-15, 2021 (virtual meeting).
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