Rheumatic heart disease secondary prophylaxis prescribing patterns and outcomes: A tertiary care hospital experience in Saudi Arabia

Namareq F Aldardeer; Amnah S Mukhtar; Bayader S Kalkatawi; Arwa F Lardhi; Nezar E Elsheikh

doi:10.4103/sjcp.sjcp_22_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 2 | Issue : 1 | Page : 4-8

Rheumatic heart disease secondary prophylaxis prescribing patterns and outcomes: A tertiary care hospital experience in Saudi Arabia

Namareq F Aldardeer¹, Amnah S Mukhtar¹, Bayader S Kalkatawi¹, Arwa F Lardhi², Nezar E Elsheikh³
¹ Pharmaceutical Care Department, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
² Cardiology Department, Dr. Suliman Fakeeh Hospital, Jeddah, Saudi Arabia
³ Cardiovascular Diseases Department, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia

Date of Submission	16-Oct-2022
Date of Acceptance	21-Feb-2023
Date of Web Publication	30-Mar-2023

Correspondence Address:
Namareq F Aldardeer
Pharmaceutical Care Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 40047, Jeddah 21499 MBC J-11
Saudi Arabia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/sjcp.sjcp_22_22

Abstract

Background: Rheumatic heart disease (RHD) is a leading cause of heart disease in children and young adults in developing countries and is considered a significant cause of cardiovascular diseases. Antimicrobial prophylaxis is recommended as secondary prevention for heart complications caused by recurrent acute rheumatic fever. Objective: Our study aims to describe the prescribing patterns of RHD antibiotic secondary prophylaxis among eligible patients and highlight the frequency of valvular heart disease complications requiring intervention. Materials and Methods: A single-center retrospective study was conducted at a tertiary hospital in Saudi Arabia. The study included all patients 5 years old and above diagnosed with rheumatic heart fever and/or RHD and eligible for secondary prevention between January 2009 and December 2018. The primary outcome is the frequency of RHD secondary prophylaxis prescribed for eligible patients. Results: Among 806 patients who were screened, 272 patients were eligible for inclusion. A total of 194 (71.3%) were female, and 146 (53.67%) were older than 40. RHD secondary prophylaxis prescribing adherence was found in only 14 of 272 (5.14%). A total of 185 of 272 (68%) patients had at least one cardiac-related intervention during the follow-up period. Valvular heart disease progression was found in 72 of 185 (38.9%) after a primary intervention. Overall mortality was 30 (11%). Conclusion: Our study found low prescribing adherence to RHD secondary prevention among eligible patients in an area with a high disease prevalence. A larger sample size is needed to confirm these findings.

Keywords: Antibiotic prophylaxis, rheumatic fever, rheumatic heart disease, secondary prevention

How to cite this article:
Aldardeer NF, Mukhtar AS, Kalkatawi BS, Lardhi AF, Elsheikh NE. Rheumatic heart disease secondary prophylaxis prescribing patterns and outcomes: A tertiary care hospital experience in Saudi Arabia. Saudi J Clin Pharm 2023;2:4-8

How to cite this URL:
Aldardeer NF, Mukhtar AS, Kalkatawi BS, Lardhi AF, Elsheikh NE. Rheumatic heart disease secondary prophylaxis prescribing patterns and outcomes: A tertiary care hospital experience in Saudi Arabia. Saudi J Clin Pharm [serial online] 2023 [cited 2023 Jun 10];2:4-8. Available from: http://www.sjcp.org/text.asp?2023/2/1/4/372929

Introduction

Rheumatic heart disease (RHD) is an immunological reaction to group A streptococcus (GAS) infection. It develops 2–3 weeks post acute pharyngitis and attacks certain body parts, including the heart, joints, brain, and skin.^[1] Acute rheumatic fever (ARF), however, occurs after evidence of preceding streptococcal infection.^[2],[3] According to the World Health Organization, RHD and ARF are considered significant causes of cardiovascular diseases.^[4] In 2015, there were globally 33.4 million cases of RHD with 319,400 deaths.^[5] Although RHD has significantly reduced in developed countries, it remains a significant concern in regions such as Africa, South-Central Asia, and Arabian Gulf, including Saudi Arabia.^[6]

Secondary prevention of recurrent ARF with lifelong antibiotic prophylaxis is recommended for patients with a definite history of ARF or diagnosis of definite RHD. Secondary antimicrobial prevention protects patients against reinfection with GAS, thus preventing recurrent ARF and the risk of heart complications and further damage to the heart valves.^{[7],[8],[9],[10]} A Cochran review of three trials (n = 1301) compared penicillin with control as prevention of ARF. One of the three studies showed that penicillin decreased the recurrence of rheumatic fever (RF) (RR, 0.45; 95% confidence interval [CI], 0.22–0.92) and GAS infection (RR, 0.84; 95% CI, 0.72–0.97).^[11]

The 2009 American Heart Association scientific statement and the 2017 RHD Saudi guidelines thoroughly described the eligibility criteria for RHD secondary prevention.^[6],[7] However, the secondary antibiotic prophylaxis prescribing in literature was low and ranged between 18% and 54%.^[12],[13] Despite the high prevalence of RHD in our population, there is a lack of enforcement systems for secondary prophylaxis initiation for eligible patients, which necessitates evaluating the risk of nonadherence to the prescription of RHD prevention. Our study aims to describe the prescribing patterns of RHD antibiotic secondary prophylaxis among eligible patients and highlight the frequency of overall valvular heart disease complications requiring intervention.

Patients and Methods

A descriptive retrospective study was conducted at a 500-bed tertiary care hospital in Saudi Arabia. The study included all patients 5 years old and above diagnosed between 2009 and 2018 with RF and/or RHD and eligible for secondary prevention based on the published guidelines.^[6] We defined rheumatic heart fever as an infection with body temperature reaching 38.2°C–38.9°C post-GAS infection.^[1],[14] We considered patients eligible for secondary antibiotic prevention in the following cases: RF with carditis and residual heart disease (persistent valvular disease evidenced clinically or echocardiographically); RF with carditis but no residual heart disease (no valvular disease evidenced clinically or echocardiographically); RF with carditis but no residual heart disease (no valvular disease evidenced clinically or echocardiographically); or RF without carditis.^[6],[7] The study excluded patients who did not qualify for secondary prevention [Figure 1]. The hospital’s institutional review board approved the study.

Figure 1: Patient enrollment

Click here to view

We used the hospital system Citrix to identify RHD/RF patients. We collected data on patient demographics, antibiotic prophylaxis adherence, valvular complications, and surgery history for valvular heart diseases using the research electronic data capture system.

The primary outcome is the frequency of RHD secondary prophylaxis prescribed for eligible patients. Secondary outcomes include the frequency of valvular heart disease interventions, the number of valvular heart disease progression after the first and second interventions, the time from the first and second intervention to further valvular disease progression, and overall mortality. We used simple descriptive statistics using frequencies and percentages for the categorical data, including baseline characteristics and outcomes.

Results

A total of 806 patients with RHD were screened between January 2009 and December 2018. The analysis included 272 patients who fit the inclusion criteria. Most of the included patients were female, 194 (71.3%), and around 146 (53.67%) were more than 40 years old. Upon hospital referral, most patients were newly diagnosed, 164 (60.29%), and only 22 (8.08%) received secondary antibiotic prevention. Most study patients were followed up for more than 5 years, 181 (66.54%) [Table 1].

Table 1: Baseline characteristics for eligible patients upon hospital referral (n = 272)

Click here to view

RHD secondary prevention prescribing was found in only 14 (5.14%) eligible patients. The valve-related surgery interventions were performed in 185 of 272 (68%) patients. Type of valvular interventions includes mechanical valve replacement (103 [55.6%]), valve repair (61 [32.9%]), tissue valve replacement (54 [29.1%]), and valve dilatation (14 [7.5%]). Valvular heart disease progression was found in 72 of 185 (38.9%) after a primary intervention. Valve regurgitation was the most form of progression (39 [54.1%]). In most patients with valvular intervention, the time to first progression was less than 5 years, 35 of 74 (47.29%). Progression after the secondary intervention was found in 13 of 35 (37.14%) patients. Overall mortality was 30 (11%) among included patients [Table 2].

Table 2: Eligible patients’ interventions and outcomes during study follow-up

Click here to view

Discussion

Our descriptive study highlighted the extremely low prescribing of RHD secondary prevention, which was observed in only 14 (5.14%) eligible patients. Nationally, a retrospective study (n = 1094) aimed to highlight the impact of RHD secondary prevention on patient outcomes found that only 18% of patients were prescribed antibiotic prophylaxis. At a 10-year follow-up period, the propensity score matching analysis found no significant difference in overall survival, valve-related hospitalization, and redo valve surgery between those who received the prophylaxis and those who did not.^[12] Internationally, many studies encountered patients’ adherence rate to RHD secondary prevention rather than physician-prescribing adherence. In a retrospective Brazilian study of 536 patients, 31% had a recurrence because antibiotics were not prescribed. On the other hand, among patients who received secondary antibiotic prevention and had a recurrence, 54.5% were nonadherent to antibiotic prophylaxis, and 14.5% of patients adhered to secondary prevention.^[15] In the global rheumatic heart disease registry (REMEDY) study, 54.8% of patients received secondary prevention, and 78% adhered to therapy; adherence was defined as having received greater than or equal to 80% of the prescribed doses in the preceding year. At 2 years, patients prescribed secondary antibiotic prophylaxis were less likely to have ARF, new onset of congestive heart failure, or die (16.2% versus 20.7%, P = 0.001).^[16] Indeed, a recent study by Rémond et al.^[9] discussed using the Chronic Care Model to solve poor compliance with RHD prophylaxis. This model includes self-management support, delivery system design, decision support, and clinical information system. These involve suggested interventions by patients, families, healthcare providers, and technology to optimize RF/RHD prevention.^[9]

Nonvalvular heart disease complications related to RHD include atrial fibrillation, pulmonary hypertension, infective endocarditis, congestive heart failure, and stroke.^[17] Among our patients, 185 of 272 (68%) had at least one heart-related surgical intervention in the form of valve replacement, repair, and/or dilatation. In the REMEDY study, the majority (63.9%) of patients had moderate-to-severe multivalvular disease.^[7] The choice of surgical intervention (replacement vs. repair) is debated in the literature. The primary concern about the type of surgery in young patients is the questionable compliance to anticoagulation therapy and secondary antibiotic prophylaxis.^[7] However, in the Australian cardiac surgery database, RHD mitral valve repair and replacement were no different (hazard ratio [HR], 0.86; 95% CI, 0.4–1.7) in the unadjusted survival analysis.^[18]

Our study investigated RHD progression and mortality. In our data, overall mortality was 11% among RHD patients. In REMEDY, the mortality rate reached 16.9%, with the median age at death being 28.7 years old. Severe valve disease was an independent predictor of death (HR, 2.36; 95% CI, 1.80–3.11).^[19] In our study, the overall disease progression requiring surgical intervention was found in 68% of patients. Moreover, disease progression was 38.9% and 37.14% post-first and second interventions, respectively. In a registry that aimed to identify RHD disease progression in Australia, 11.4% progressed to severe cases among initial mild RHD cases, and half required surgery.^[20]

Our study is one of the few studies that tackled the prescribing patterns of RHD secondary prevention in an area of high prevalence. However, some limitations to our study need to be addressed. First, the study was conducted in a single center, which could not represent nationwide data. Second, the low number of prescribed antibiotic prophylaxis in our hospital hinders us from performing a thorough analysis comparing the outcomes of patients who received secondary antibiotic prevention and those who did not. Thus, the study mainly represents the complications and outcomes of patients who did not receive prophylaxis. Finally, the loss of follow-up prevented us from collecting long-term data. Finally, providing awareness and education to prescribers is essential to improve prescribing patterns. A nationwide campaign and encouragement by a recognized national entity could improve the healthcare provider’s perception and compliance with RHD prophylaxis prescribing.

Conclusion

Our study confirmed the low prescribing adherence to RHD secondary prevention among eligible patients in an area with a high disease prevalence. Valve-related complications and the need for valvular heart disease surgeries are found in most RHD patients. A pre- and post-RHD antibiotic secondary prevention study with a larger sample size is needed to confirm these findings.

Declarations

All authors have reviewed and agreed with the manuscript’s contents and approved publication.

Ethical statement

The institutional review board of the hospital approved the study.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Financial support and sponsorship

Nil.

Conflicts of interest

The authors have no conflicts of interest to declare.

References

1.	Liu M, Lu L, Sun RR, Zheng Y, Zhang P Rheumatic heart disease: Causes, symptoms, and treatments. Cell Biochem Biophys 2015;72:861-3.
2.	Gewitz MH, Baltimore RS, Tani LY, Sable CA, Shulman ST, Carapetis J, et al. Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: A scientific statement from the American Heart Association. Circulation 2015;131:1806-18.
3.	Ralph AP, Noonan S, Wade V, Currie BJ The 2020 Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease. Med J Aust 2021;214:220-7.
4.	Itzikowitz G, Prendergast EA, Prendergast BD, Zühlke L Acute rheumatic fever and rheumatic heart disease. Hear Valve Dis State Art 2001;2019:163-75.
5.	Watkins DA, Johnson CO, Colquhoun SM, Karthikeyan G, Beaton A, Bukhman G, et al. Global, regional, and national burden of rheumatic heart disease, 1990–2015. N Engl J Med 2017;377:713-22.
6.	Al-Jazairi A, Al-Jaser R, Al-Halees Z, Shahid M, Al-Jufan M, Al-Mayouf S, et al. Guidelines for the secondary prevention of rheumatic heart disease. Int J Pediatr Adolesc Med 2017;4:47-50.
7.	Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, et al. Prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis: A scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics. Circulation2009;119:1541-51.
8.	Veasy LG, Wiedmeier SE, Orsmond GS, Ruttenberg HD, Boucek MM, Roth SJ, et al. Resurgence of acute rheumatic fever in the intermountain area of the United States. N Engl J Med [Internet] 1987;316:421-7.
9.	Rémond MGW, Coyle ME, Mills JE, Maguire GP Approaches to improving adherence to secondary prophylaxis for rheumatic fever and rheumatic heart disease: A literature review with a global perspective. Cardiol Rev 2016;24:94-8.
10.	WHO Study Group on Rheumatic Fever and Rheumatic Heart Disease (2001: Geneva S, Organization WH). Rheumatic fever and rheumatic heart disease: Report of a WHO expert consultation, Geneva, 20 October - 1 November 2001. Geneva: World Health Organization; 2004 (WHO technical report series; 923). Available from: https://apps.who.int/iris/handle/10665/42898.
11.	Manyemba J, Mayosi BM Penicillin for secondary prevention of rheumatic fever. Cochrane Database Syst Rev2002;2002:CD002227.
12.	Al-Jazairi AS, Althobaiti AM, Marek J, Devol EB, Al Halees Z, Mohty DF Does secondary antibiotic prophylaxis improve clinical outcomes in adult rheumatic heart disease patients post-valve replacement? World J Pediatr Congenit Hear Surg 2022;18:21501351221139830.
13.	Karthikeyan G, Zühlke L, Engel M, Rangarajan S, Yusuf S, Teo K, et al. Rationale and design of a global rheumatic heart disease registry: The REMEDY study. Am Heart J. 2012;163:535-40.e1.
14.	Szczygielska I, Hernik E, Kołodziejczyk B, Gazda A, Maślińska M, Gietka P Rheumatic fever—New diagnostic criteria. Reumatologia 2018;56:37-41.
15.	Pelajo CF, Lopez-Benitez JM, Torres JM, de Oliveira SKF Adherence to secondary prophylaxis and disease recurrence in 536 Brazilian children with rheumatic fever. Pediatr Rheumatol 2010;8:1-5.
16.	Zühlke L, Karthikeyan G, Engel ME, Rangarajan S, Mackie P, Cupido-Katya Mauff B, et al. Clinical outcomes in 3343 children and adults with rheumatic heart disease from 14 low-and middle-income countries: Two-year follow-up of the global rheumatic heart disease registry (the REMEDY Study). Circulation 2016;134:1456-66.
17.	Kumar RK, Antunes MJ, Beaton A, Mirabel M, Nkomo VT, Okello E, et al. Contemporary diagnosis and management of rheumatic heart disease: Implications for closing the gap: A scientific statement from the American Heart Association. Circulation 2020;142:e337-57.
18.	Russell EA, Walsh WF, Reid CM, Tran L, Brown A, Bennetts JS, et al. Outcomes after mitral valve surgery for rheumatic heart disease. Heart Asia 2017;9:e0109161-7.
19.	Zühlke LJ, Beaton A, Engel ME, Hugo-Hamman CT, Karthikeyan G, Katzenellenbogen JM, et al. Group a streptococcus, acute rheumatic fever and rheumatic heart disease: Epidemiology and clinical considerations. Curr Treat Options Cardiovasc Med2017;19:15.
20.	Cannon J, Roberts K, Milne C, Carapetis JR Rheumatic heart disease severity, progression and outcomes: A multi-state model. J Am Heart Assoc 2017;6:e003498.