How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease

Background Acute rheumatic fever (ARF) and rheumatic heart disease cause substantial burdens worldwide. Long‐term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited. Using data from northern Australia, we identi...

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Main Authors: Jessica Langloh de Dassel, Nick de Klerk, Jonathan Rhys Carapetis, Anna P. Ralph
Format: Article
Language:English
Published: Wiley 2018-12-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.118.010223
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author Jessica Langloh de Dassel
Nick de Klerk
Jonathan Rhys Carapetis
Anna P. Ralph
author_facet Jessica Langloh de Dassel
Nick de Klerk
Jonathan Rhys Carapetis
Anna P. Ralph
author_sort Jessica Langloh de Dassel
collection DOAJ
description Background Acute rheumatic fever (ARF) and rheumatic heart disease cause substantial burdens worldwide. Long‐term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited. Using data from northern Australia, we identified factors associated with adherence, and the association between adherence and ARF recurrence, progression to rheumatic heart disease, worsening or improvement of rheumatic heart disease, and mortality. Methods and Results Factors associated with adherence (percent of doses administered) were analyzed using logistic regression. Nested case–control and case–crossover designs were used to investigate associations with clinical outcomes; conditional logistic regression was used to estimate odds ratios (OR) with 95% CIs Adherence estimates (7728) were analyzed. Being female, younger, having more‐severe disease, and living remotely were associated with higher adherence. Alcohol misuse was associated with lower adherence. The risk of ARF recurrence did not decrease until ≈40% of doses had been administered. Receiving <80% was associated with a 4‐fold increase in the odds of ARF recurrence (case–control OR: 4.00 [95% CI: 1.7–9.29], case–crossover OR: 3.31 [95% CI: 1.09–10.07]) and appeared to be associated with increased all‐cause mortality (case–control OR: 1.90 [95% CI: 0.89–4.06]; case–crossover OR 1.91 [95% CI: 0.51–7.12]). Conclusions We show for the first time that increased adherence to penicillin prophylaxis is associated with reduced ARF recurrence, and a likely reduction in mortality, in our setting. These findings can motivate patients to receive doses since even relatively low adherence can be beneficial, and additional doses further reduce adverse clinical outcomes.
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spelling doaj.art-bd3096c695e24c64844b4aabad13c1422022-12-21T18:11:42ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802018-12-0172410.1161/JAHA.118.010223How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart DiseaseJessica Langloh de Dassel0Nick de Klerk1Jonathan Rhys Carapetis2Anna P. Ralph3Menzies School of Health Research Charles Darwin University Darwin AustraliaTelethon Kids Institute University of Western Australia Perth AustraliaTelethon Kids Institute University of Western Australia Perth AustraliaMenzies School of Health Research Charles Darwin University Darwin AustraliaBackground Acute rheumatic fever (ARF) and rheumatic heart disease cause substantial burdens worldwide. Long‐term antibiotic secondary prophylaxis is used to prevent disease progression, but evidence for benefits of different adherence levels is limited. Using data from northern Australia, we identified factors associated with adherence, and the association between adherence and ARF recurrence, progression to rheumatic heart disease, worsening or improvement of rheumatic heart disease, and mortality. Methods and Results Factors associated with adherence (percent of doses administered) were analyzed using logistic regression. Nested case–control and case–crossover designs were used to investigate associations with clinical outcomes; conditional logistic regression was used to estimate odds ratios (OR) with 95% CIs Adherence estimates (7728) were analyzed. Being female, younger, having more‐severe disease, and living remotely were associated with higher adherence. Alcohol misuse was associated with lower adherence. The risk of ARF recurrence did not decrease until ≈40% of doses had been administered. Receiving <80% was associated with a 4‐fold increase in the odds of ARF recurrence (case–control OR: 4.00 [95% CI: 1.7–9.29], case–crossover OR: 3.31 [95% CI: 1.09–10.07]) and appeared to be associated with increased all‐cause mortality (case–control OR: 1.90 [95% CI: 0.89–4.06]; case–crossover OR 1.91 [95% CI: 0.51–7.12]). Conclusions We show for the first time that increased adherence to penicillin prophylaxis is associated with reduced ARF recurrence, and a likely reduction in mortality, in our setting. These findings can motivate patients to receive doses since even relatively low adherence can be beneficial, and additional doses further reduce adverse clinical outcomes.https://www.ahajournals.org/doi/10.1161/JAHA.118.010223acute rheumatic feveradherenceAustralian Indigenousrheumatic heart diseasesecondary prophylaxis
spellingShingle Jessica Langloh de Dassel
Nick de Klerk
Jonathan Rhys Carapetis
Anna P. Ralph
How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
acute rheumatic fever
adherence
Australian Indigenous
rheumatic heart disease
secondary prophylaxis
title How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease
title_full How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease
title_fullStr How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease
title_full_unstemmed How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease
title_short How Many Doses Make a Difference? An Analysis of Secondary Prevention of Rheumatic Fever and Rheumatic Heart Disease
title_sort how many doses make a difference an analysis of secondary prevention of rheumatic fever and rheumatic heart disease
topic acute rheumatic fever
adherence
Australian Indigenous
rheumatic heart disease
secondary prophylaxis
url https://www.ahajournals.org/doi/10.1161/JAHA.118.010223
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