Project Details

Determining the Impact of Penicillin on Latent Rheumatic Heart Disease

Andrea Beaton, MD

Summary

BACKGROUND: Rheumatic heart disease (RHD) is a cumulative heart valve disease that results from Group A streptococcal infection, triggering the systemic inflammatory condition acute rheumatic fever (ARF), mainly in children, and leading to chronic cardiac valve disease. GAP: Echocardiography can “see” latent RHD before symptoms develop, allowing for early disease detection and initiation of benzathine penicillin G (BPG) prophylaxis. While BPG prophylaxis is known to stop disease progression and cause disease regression among patients with ARF, its effect on latent RHD is not known. HYPOTHESIS: Hypothesis 1: Prophylaxis with BPG will result in fewer children with latent RHD showing progression of echocardiographic valve changes at 2 years compared to children with latent RHD not receiving BPG prophylaxis. (We expect at least a 50% relative reduction in progression in the BPG arm: range 15%-25% control arm vs. 7.5-12.5% BPG-arm.); Hypothesis 2: Prophylaxis with BPG will result in more children with latent RHD showing regression of echocardiographic valve changes by 2 years compared to children with latent RHD not receiving BPG prophylaxis. (We expect at least a 50% relative increase in regression in the BPG arm: range 10-20% control arm vs. 20-40% BPG arm.) METHODS: We conducted a randomized controlled trial of penicillin prophylaxis in children (5-17 years) with latent RHD according to the 2012 World Heart Federation (WHF) criteria. RESULTS: A total of 916 children were enrolled between July and November 2018, meeting the enrollment target within the planned time frame. 818 were included in the modified intention to treat analysis and 799 participants (97.7%) reached study completion. Three participants in the prophylaxis group (0.8%) demonstrated echocardiographic progression, compared to 33 (8.3%) in the control group (risk difference -7.5%, 95%CI, -10.2 to -4.7, p<0.001). The number of children with latent rheumatic heart disease needed to receive prophylaxis to prevent one child from developing progression was 13 (95%CI, 10 to 21). There were 2 serious adverse events in the prophylaxis group, including one episode of a mild anaphylactic reaction (0.01% of all treatment doses). IMPACT: Secondary antibiotic prophylaxis reduces the risk of latent rheumatic heart disease progression at 2 years. These data provide new information for our understanding of the role of screening for latent rheumatic heart disease. Further research is needed before the implementation of population-level screening can be recommended.

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