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Curr Cardiol Rev
Curr Cardiol Rev
CCR
Current Cardiology Reviews
1573-403X
1875-6557
Bentham Science Publishers

38018202
CCR-20-E231123223747
10.2174/011573403X256576231017110252
Medicine, Cardiology
Adherence to Congestive Heart Failure Guidelines and Outcome in the Middle East
Aqel Raed 1*
Alzughayyar Tareq 2
Zalloum Jihad 3
Salah Qais 3
Qafisheh Qutaiba 2
Izraiq Mahmoud 4
1 National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan;
2 College of Medicine and Health Sciences, Palestine Polytechnic University, Hebron, Palestine;
3 Faculty of Medicine, Al Quds University, Jerusalem, Palestine;
4 The Specialty Hospital, Private Sector, Amman, Jordan
* Address correspondence to this author at the National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan; E-mail: raed.aqel@yahoo.com
23 11 2023
2024
23 11 2023
20 3 E23112322374709 4 2023
18 7 2023
28 8 2023
© 2024 The Author(s). Published by Bentham Science Publisher.
2024
The Author(s)
https://creativecommons.org/licenses/by/4.0/ © 2024 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Background

Adherence to Congestive Heart Failure with reduced Ejection Fraction (CHFrEF) guidelines is not easily attainable everywhere, particularly in countries with a high prevalence of low socioeconomic status, which includes many Middle Eastern countries. However, it is well-established that adherence to the guidelines is associated with lower mortality and morbidity rates.

Objective

Our objective is to investigate the adherence to the degree of treatment guideline in CHFrEF within a patient population in the Middle East and correlate the level of compliance both fully and partially with morbidity and mortality outcomes.

Methods and Statistics

We conducted a retrospective study on patients with CHFrEF in the Middle East region who were maintained on Sacubitril/Valsartan for up to 4 years (190 patients). This study included follow-up assessments for morbidity and mortality rates and their correlation with the level of adherence to guidelines.

Results

Statistical analysis was performed using IBM SPSS® 27th version. In both the partial adherence group and the full adherence group, there was a statistically significant improvement in NYHA (pretreatment and post-treatment) and Ejection fraction (pretreatment and post-treatment). This means that regardless of the level of adherence to the use of Sacubitril/Valsartan in CHFrEF, there was an overall improvement in the morbidity and mortality rates over the four years of follow-up.

Conclusion

While we fully support the idea of achieving full CHFrEF guideline adherence, we recognize the difficulty of this task. Nevertheless, this study reinforces the notion that any degree of adherence to guideline is correlated with better morbidity and mortality rates over a long-term follow-up.

Keywords

Congestive
heart failure
guidelines
Middle East
socioeconomical
ejection fraction
morbidity and mortality rates
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pmc1 INTRODUCTION

Adherence to guideline is often linked to improved morbidity and mortality rates- a promising prospect for better health outcomes. However, the reality is far from simple. Multiple studies have revealed that strict or complete adherence to guidelines is an unfeasible task for both patients and physicians. Interestingly, institutional guidelines have been shown to influence physician adherence, which ranges from 25% to 50%, with academic institutions reporting the highest rates. Moreover, patients' adherence to guidelines is even lower, rarely surpassing 30%. This phenomenon, known as “adherence fatigue,” is a culmination of various factors, including the complexities of long-term medication use, its high costs, diverse side effects, low socioeconomical status and even physician adherence, as reflected in the time invested in patients’ education [1, 2].

The aftermath of the PARADIGM-HF and PROVE-HF studies triggered a surge of interest in the global and local efficacy of Sacubitril/Valsartan. In the Middle East, data on CHFrEF incidence, guideline application, and long-term morbidity and mortality have been rapidly accumulating. We have previously revealed eye-opening one-year follow-up data on ejection fraction improvement in Palestinian patients with CHFrEF [3]. A recent pilot study, published in 2021, offers promising results, showcasing improved morbidity and mortality rates over four years in Middle Eastern patients with CHFrEF on Sacubitril/Valsartan [4-6].

Currently, it is well-established that Sacubitril/Valsartan treatment leads to significant improvement in cardiac remodeling parameters, particularly an increase in left ventricular ejection fraction, as well as improvements in left ventricular and left atrial volumes and diastolic function [7]. These positive changes are associated with lower rates of hospitalization and mortality during follow-up.

Researchers are now exploring new areas of understanding regarding Sacubitril/Valsartan, including patients’s adherence levels and serum biomarkers and their association with clinical outcomes. For example, many experts propose a stronger association with levels of atrial natriuretic peptide (ANP), which nearly doubles in less than one month after treatment initiation. This suggests that ANP might be a more accurate marker than the inert, non-active NT-proBNP mediator in assessing treatment response and clinical outcomes [7].

In this manuscript, we seek to shine a light on the degree of adherence to guidelines for CHFrEF in the Middle East and its direct correlation with morbidity and mortality over a follow-up period of up to 4 years. This represents a new area of research, building upon our previous studies, with the hope of advancing our understanding and enhancing healthcare outcomes in the region.

2 METHODS

This single-center retrospective review study was conducted at a referral cardiologist clinic in the West Bank, Palestinian Territories. The data for all patients diagnosed with CHFrEF and maintained on the maximum dose of sacubitril/valsartan, following the recommendations of the Paradigm HF study [8] and the current CHFrEF guidelines [9], were collected.

All patients willingly consented to participate in this study and signed an informed consent form after being fully informed about the study protocols and objectives.

Data from all subjects' clinic visits, phone correspondences, laboratory studies, and echocardiogram results were meticulously tabulated over a follow-up period ranging from 6 months to four years.

The ejection fraction was accurately calculated by at least two board-certified cardiologists using M-Mode and/or the modified Simpson formula.

For data analysis, IBM SPSS® Statistics was employed, along with the normality test and paired T-test. The p-value for NYHA and the ejection fraction before and after medication was calculated for both the full adherence and partial adherence groups.

2.1 Inclusion Criteria

Ages above 18 years.

Documented CHFrEF diagnosis.

Sacubitril/valsartan usage for at least six months between January 1, 2016, and June 30, 2019.

Left ventricular ejection fraction (LVEF) less than or equal to 40%.

2.2 Exclusion Criteria

Ages below 18 years.

LVEF greater than 40% before starting sacubitril/valsartan therapy.

Pregnant women.

Taking Sacubitril/Valsartan for less than six months.

Inability to obtain informed consent.

3 RESULTS

Among the 190 patients included in this study, follow-up was completed for 187 patients (98%), while three patients (2%) were lost to follow-up by the end of the study. A total of 156 patients (82%) were titrated to 200 mg BID of Sacubitril/valsartan, and 34 patients (18%) were titrated to 100 mg BID of sacubitril/valsartan, with follow-ups every three months until the study's conclusion. Throughout the study, patients' adherence to prescribed doses was recorded, revealing that only 38 patients (20%) adhered fully to the prescribed doses, while approximately 152 patients (80%) exhibited partial adherence, which included temporary medication holds and/or dose reductions. Notably, no patients were without any adherence, thanks to the intensive follow-up protocol. By the end of the study, 23 patients (20 from the partial adherence group (13%) and three (3%) from the full adherence group) had passed away.

IBM SPSS® Statistics was utilized for data analysis, employing the normality test and paired T-test. The results demonstrated that the p-value for NYHA before and after medication delivery was 0.0001 in the partial adherence group (statistically significant) and 0.0001 in the full adherence group (also statistically significant). Similarly, the p-value for ejection fraction before and after medication delivery in the partial adherence group was 0.0001 (statistically significant), and 0.0009 in the full adherence group (also statistically significant).

This implies that any level of partial adherence provided a benefit in both NYHA score and EF values.

All data, including Quality of Life (QOL) described by the New York Heart Association's (NYHA) heart failure classification, laboratory data, transthoracic echocardiographic data, and mortality rate, were meticulously tabulated.

For detailed information, please refer to Tables 1A, 1B, 2 and 3 as well as Figs. (1 and 2).

4 DISCUSSION

Guidelines are meticulously crafted after extensive research and a thorough review of past and recent literature, all with the aim of maximizing the benefits patients can achieve. While these guidelines stress the importance of adherence to improve outcomes, it is essential to acknowledge that full adherence is not always attainable, especially in economically challenged countries where education and socioeconomic conditions may play a significant role [10, 11].

The focus of research on adherence to chronic illness treatment guidelines has largely centered around common conditions like hypertension, diabetes, and dyslipidemia. Surprisingly, close to half of the studied patients (40-65%) did not fully adhere to their prescribed medications, thereby missing out on the full benefits of their therapies [12].

Historically, poor adherence to guideline therapies has been linked to four primary factors: The patient's socioeconomic status and cultural background, the doctor-patient relationship, the patient's employment and family situation, and the complexity of the prescribed treatment [5, 11, 13].

The Qualify Registry's publication in 2017 shed light on physicians' adherence to guidelines, which ranged from 20-58%, with higher adherence observed in academic institutions. This lack of full-scale adherence is not exclusive to poorer countries; developed nations also face challenges with physician and patient adherence due to various factors [14].

Additionally, research by Rasmusoon et al. shows that depressive symptoms and a decline in health-related quality of life are linked to patients not taking their heart failure medications as prescribed. Health-related quality of life and depressive symptoms are two indicators that can be used to better tailor care for individuals with heart failure and thereby boost their prognosis [15].

In the Middle East, our group was among the pioneers in describing the challenges of CHFrEF, its short- and long-term follow-up, and its impact on morbidity and mortality [5]. Our pilot study revealed that achieving full adherence to guideline, even in well-established medical systems, is practically impossible. Despite taking all precautions, and implementing stringent follow-up measures, we could only achieve up to 20% full adherence. Economic burdens on patients and government budgets were among the major obstacles in our region. Additionally, common challenges, such as patient fatigue, limited education, medication side effects, lack of family support, religious beliefs influencing medical decisions, and poor physician adherence to guidelines, were prevalent [16, 17].

In our study, we questioned whether the poor adherence to CHrEF guidelines in our region would negatively affect the morbidity and mortality rates of these patients. Surprisingly and unintentionally, our findings demonstrated that any level of adherence led to improved morbidity and mortality outcomes for these patients. However, due to the small sample sizes in each medication dose group, we couldn't make direct comparisons between them. We also lacked a placebo sample, but we compensated for this limitation by comparing our mortality results with historical controls. Furthermore, we aspire to delve into the intricacies of the relationship between natriuretic peptide levels, specifically B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP), and their direct correlation to patient adherence. Moreover, we envisage the possibility of incorporating drug-level analysis to gain a profound understanding of true adherence. Regrettably, due to the poor financial status of the majority of our patients and the high pricing of this test in our country, we find ourselves unable to embark on this ambitious endeavor. Nonetheless, we deem this new avenue of research to be of paramount importance and shall remain an eminent priority in our ongoing exploration of the therapeutic potential of sacubitril/valsartan [7, 18].

Above all, throughout the study, our intention was never to recommend partial adherence to CHFrEF guidelines. Rather, we aimed to stress the importance of full adherence while acknowledging the reality of encouraging any degree of adherence to guideline, considering the challenges faced globally and particularly in our part of the world, where legitimate reasons hinder full-scale adherence—a reality disconnect. This term refers to the realization that a world where full-scale adherence is universally achieved does not exist.

CONCLUSION

Our pilot study highlighted the challenging nature of achieving full-scale adherence to guidelines, acknowledging that it is a difficult and ambitious task. In this reality-disconnected world, we need to be more realistic in setting our goals. Our focus should be on encouraging patients to achieve the highest level of adherence they can, recognizing that any level of adherence is valuable and can positively impact their outcomes. We should continue to motivate them to improve because every effort towards adherence matters, and it can make a significant difference in their health journey.

ACKNOWLEDGEMENTS

Declared none.

AUTHORS’ CONTRIBUTIONS

All authors contributed equally to the manuscript.

LIST OF ABBREVIATIONS

ANP Atrial Natriuretic Peptide

QOL Quality of Life

NYHA New York Heart Association's

BNP B-type Natriuretic Peptide

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This study was conducted in compliance with all the applicable as per the Al Quds University Faculty of Medicine Jerusalem Palestine, institutional ethical guidelines for the care, and welfare of subjects.

HUMAN AND ANIMAL RIGHTS

All procedures performed in studies involving human participants were in accordance with the ethical standards of institutional and/or research committee and with the 1975 Declaration of Helsinki, as revised in 2013.

CONSENT FOR PUBLICATION

Informed consent was obtained from all participants.

STANDARDS OF REPORTING

STROBE guidelines were followed.

AVAILABILITY OF DATA AND MATERIALS

The data supporting this study's findings are openly available upon request.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

Fig. (1) LVEF pretreatment and post-treatment in full & partial adherence groups.

Fig. (2) NYHA pretreatment and post-treatment in full & partial adherence groups.

Table 1A Patients’ background for the full adherence group.

Patients’ Background	Number of Patients	
Ischemia	24	
HTN	22	
DM	20	
AICD	2	
CRTD	1	
AF	8	
Smoking	14	

Table 1B Patients’ background for the partial adherence group.

Patients’ Background	Number of Patients	
Ischemia	100	
HTN	97	
DM	75	
AICD	16	
CRTD	7	
AF	21	
Smoking	46	

Table 2 Transthoracic echocardiographic data.

	Full Adherence	Partial Adherence	
	Pre-treatment	Post-treatment	Pre-treatment	Post-treatment	
Left ventricular ejection fraction	31	42	30	39	
New York Heart Association	3.2	1.8	3	1.8	

Table 3 Mortality rate.

Alive	167	
Deceased	23	
No follow-up	3
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