JFOA Journal

Thematic Elements

Adherence to guidelines: Most sources addressing ACEIs and ARBs emphasize compliance with clinical guidelines. The ACC, AHA, and ESC provide detailed guidelines that highlight specific criteria for initiating and managing methods to enhance patient outcomes. Maintaining adherence to these established procedures is crucial for attaining optimal clinical outcomes (American College of Cardiology, 2021; ACC & AHA, 2017; ESC, 2021).

Patient Outcomes: The research emphasizes assessing the efficacy and safety of ACE inhibitors and angiotensin receptor blockers. Research published in Diabetes Care and Kidney International highlights the importance of continuous assessment of patient responses, necessitating treatment modifications to ensure safety, particularly regarding renal function and glycemic control in highrisk groups, such as diabetic patients (Diabetes Care, 2018; Kidney International, 2019).

Variations in clinical practice: Articles by Singh et al. (2025) and Circulation (2023) address variations in clinical practice. They discuss practical issues such as patient adherence to medication, the management of side effects, and adjustments based on individual responses. These studies demonstrate that practical implementations may vary based on individual patient conditions and physician discretion, despite published recommendations, leading to variability in practice.

Special Populations: Pregnant and diabetic patients necessitate customized strategies for managing ACEIs and ARBs. The American Journal of Obstetrics and Gynecology (2020) discussed the potential risks associated with the use of certain antihypertensive drugs during pregnancy, specifically ACE inhibitors and ARBs, emphasizing the importance of alternative therapies and careful monitoring to reduce fetal risk. More recent research from the ESC Registry of Pregnancy and Cardiac Disease (ROPAC) raises similar concerns, with van der Zande et al. (2024) documenting the effects of ACE inhibitor and ARB exposure in pregnant women and emphasizing the significance of guideline-directed therapy.

Emerging Evidence and Trends: Recent evidence and trends underscore the changing role of ARBs in managing cardiovascular disorders. Recent studies in Circulation (2023) and the Journal of Clinical Hypertension (2024) suggest a growing body of evidence supporting modifications in the use of these medications. Recent discoveries necessitate the modification of therapeutic approaches in response to the latest clinical developments.

Summary of Key Findings

Appropriateness Before Initiation of ACEIs or ARBs: In their 2021 guidelines, the ACC underscored the importance of evaluating patient-specific characteristics, including blood pressure levels, heart failure, diabetic nephropathy, and the risk of cardiovascular events, prior to using ACEIs or ARBs. Clinical guidelines and patient tolerance should guide the initiation of these medications. These drugs are recommended for patients with hypertension, heart failure, and chronic kidney disease, with special consideration given to those with high cardiovascular risk (American College of Cardiology, 2021). Li et al. (2021) systematically reviewed the suitability of ACE inhibitors and angiotensin receptor blockers, emphasizing the importance of evaluating baseline renal function, blood pressure, and co-morbidities. They emphasized the significance of personalized risk evaluation and clinical discernment. They endorsed the utilization of ACEIs and ARBs under recognized standards, emphasizing patient history and current health condition. Singh et al. (2025) examined the use and management of ACEIs and ARBs, highlighting the need to assess cardiovascular disease history, renal function, and potential drug interactions before commencing treatment. It is advised to initiate therapy following a thorough risk assessment that includes variables such as age, comorbidities, and baseline blood pressure. The 2017 ACC and AHA guidelines established definitive limits for the initiation of ACEIs and ARBs, especially for patients with hypertension and other risk factors like diabetes or cardiovascular disease. These guidelines emphasize attaining target blood pressure objectives and minimizing cardiovascular incidents, incorporating patient-specific modifications as necessary (ACC & AHA, 2017). Finally, the ESC (2021) guidelines for heart failure care specified criteria for initiating ACEIs and ARBs, particularly for patients categorised by the New York Heart Association (NYHA) functional class and left ventricular ejection fraction. These drugs are highlighted for their role in alleviating symptoms and reducing mortality in patients with heart failure (European Society of Cardiology, 2021).

Relevance and Appropriateness During Continuous Treatment: The ACC (2021) advised continuous surveillance for adverse effects, including hypotension, alterations in renal function, and electrolyte disturbances, alongside regular followups and dosage modifications contingent on the patient’s response. Li et al. (2021emphasized the necessity of monitoring adherence, addressing side effects, and conducting periodic assessments of treatment efficacy, guiding mitigating adverse effects and ensuring therapeutic compliance. Singh et al. (2025) further elaborate on techniques to enhance adherence, manage prevalent side effects, and modify medication based on patient input and laboratory findings, emphasising the need for patient education. The ACC and AHA (2017) emphasized the need to adhere to treatment procedures during therapy, concentrating on monitoring side effects, regular blood pressure management, and cardiovascular risk evaluations. Likewise, the ESC (2021) recommended adjusting dosages based on symptom improvement, adverse reactions, and changes in heart failure status. Pregnant patients get special attention, as indicated in a systematic study published by the American Journal of Obstetrics and Gynaecology (2020) (Buawangpong et al., 2020). The review examined the hazards associated with the use of ACEIs and ARBs during pregnancy, advocating for alternate therapies and vigilant oversight (Buawangpong et al.,2020). Buawangpong et al. (2020) conducted a systematic assessment of the teratogenic risks associated with first-trimester exposure to ACE inhibitors and ARBs, highlighting unfavorable pregnancy outcomes and emphasizing the importance of alternate therapy and close clinical monitoring. Regarding long-term monitoring, Kidney International (2019) investigated the effects of ACEIs and ARBs on renal outcomes, emphasising the need for routine kidney function assessments and dosage adjustments. The 2018 Diabetes Care study examined the continuous management of these drugs in patients with diabetes, emphasising glucose control monitoring and potential renal adverse effects. The Journal of the ACC (2022) assessed the efficacy of ACEIs and ARBs in patients with heart failure and preserved ejection fraction (HFpEF). It advised continual modifications based on patient responses. Circulation (2023) examined the evolving role of ARBs in managing cardiovascular disease, emphasising the need for ongoing monitoring and medication adjustments. The Journal of Clinical Hypertension (2024) evaluated contemporary approaches to managing ACEIs and ARBs, identified research gaps, and proposed future avenues to enhance treatment strategies.

Discussion

We assessed eleven studies to underscore the significance of the findings. We summarise the best evidence of the appropriateness of ACEIs and ARBs before initiation and during treatment across the eight main areas addressed in this review. These include (1) effectiveness in cardiovascular disease management, (2) guideline recommendations, (3) comparison of ACEIs and ARBs, (4) safety and tolerability, (5) impact on renal outcomes, (6) clinical practice and management, (7) pregnancy considerations, and (8) future directions. In addition to the interpretation of the results, we also discuss the limitations and strengths.

Eight Main Areas Addressed in this Review

Effectiveness in Cardiovascular Disease Management: ACEIs and ARBs are extensively utilized to treat hypertension, heart failure, and chronic kidney disease, substantiating their efficacy by substantial data (American College of Cardiology, 2021; Circulation, 2023). Research indicates that ACEIs and ARBs significantly diminish cardiovascular morbidity and death by decreasing blood pressure and safeguarding target organs, including the heart and kidneys (Oparil et al., 2018). The efficacy of these medications is improved when treatment is customized to patients’ specific characteristics and comorbidities, such as diabetes or heart failure (Burnier & Egan, 2019).

Guideline Recommendations: Guidelines from significant societies such as the ACC (2017), the AHA (2017), and the ESC (2021) recommend their use as first-line therapies in these conditions, particularly emphasizing individualized treatment plans based on comorbidities and patient response (ACC & AHA, 2017; ESC, 2021). Current clinical guidelines advocate ACEIs and ARBs as first-line treatments for hypertension, heart failure with reduced ejection fraction, and chronic kidney disease (Whelton et al., 2018). These guidelines also recommend regular assessment of renal function and serum potassium concentrations to prevent adverse consequences, such as hyperkalaemia and renal dysfunction (National Institute for Health and Clinical Excellence [NICE], 2019). The incremental titration of these medications from low doses is crucial to mitigate risks and ensure effective therapeutic outcomes. Clinicians must meticulously evaluate these aspects before prescribing these drugs for extended use, with a strong emphasis on patient safety. Assessing baseline renal function and serum electrolytes is essential when initiating ACEIs or ARBs (National Institute for Health and Clinical Excellence [NICE], 2018 and 2019). Follow-up tests should be conducted one to two weeks after initiation and after dose increases (Ritter, 2011). In patients with hypertension, renal function and electrolyte levels should be monitored annually once treatment is established. In patients with CHF, monitoring should occur within days of changes in condition or medication. Once the patient is stable, monitoring should occur at least every six months (NICE 2018 and 2019). Additional monitoring is necessary for patients with comorbidities, those on specific medications, or those receiving ACEIs and ARBs (Ritter, 2011; BNF, 2024). Studies have shown that recommendations for biochemical monitoring are frequently not followed, which can lead to severe adverse events. One study indicated that merely 59% of patients prescribed ACEIs for hypertension underwent baseline monitoring, whereas only 38% received any further monitoring (Coleman et al., 2010).

Comparison of ACEIs and ARBs: The comparative efficacy of ACEIs and ARBs remains under examination. Although both drug classes offer substantial cardiovascular and renal benefits, ARBs may be preferred for patients who exhibit sensitivity to ACEIs, primarily due to the prevalence of cough as a side effect (Diabetes Care, 2018; Journal of Clinical Hypertension, 2024). Their modes of action and side effect profiles differ. ACEIs inhibit the transformation of angiotensin I into angiotensin II, whereas ARBs specifically obstruct the angiotensin II type 1 receptor. This distinction suggests that ACEIs are associated with an increased risk of cough and angioedema resulting from bradykinin accumulation (Yancy et al., 2017). Conversely, ARBs typically exhibit a more advantageous safety profile. They are less prone to induce severe side effects, rendering them an appropriate choice for those who cannot endure ACEIs. Notwithstanding these distinctions, both categories of medications confer comparable long-term cardiovascular and renal advantages, rendering them interchangeable in numerous therapeutic situations (Messerli et al., 2018).

Safety and Tolerability: The safety profiles of these agents differ (Singh et al., 2025), while effective, have been linked to higher rates of adverse events like cough, angioedema, and, less commonly, renal dysfunction. ARBs are generally better tolerated but may still cause hyperkalaemia and renal impairment in highrisk patients, such as those with chronic kidney disease or diabetes. (Fu et al., 2021). Combination therapy utilizing ACEIs and ARBs has been demonstrated to elevate the risk of severe adverse effects, such as hypotension and acute renal injury, without providing substantial extra advantages (Makani et al., 2013).  A reduced dose should be sustained if maximum doses are intolerable to guarantee therapeutic benefits (Yancy et al., 2017).

Effects on Kidneys: Notably, both drug classes exhibit beneficial renal results, particularly in individuals with diabetic nephropathy, as they decelerate the progression of kidney disease and diminish the likelihood of end-stage renal failure (Kidney International, 2019). Research indicates that these medications mitigate nephropathy progression by decreasing glomerular filtration pressure and proteinuria (Vejakama et al., 2017), while enhancing renal function and delaying the onset of end-stage renal disease (Pugh et al., 2019). Monitoring renal function and electrolyte levels is crucial to avert problems such as hyperkalemia, especially in patients with compromised kidney function. In patients with renal impairment, fosinopril is an appropriate option because it is excreted through both renal and fecal pathways. Additional ACE inhibitors, including captopril, enalapril, lisinopril, and ramipril, are also applicable for use in dialysis (Singh et al., 2025).

ACEIs and ARBs in Clinical Practice and Management: In clinical practice, determining treatment, including ACEIs and ARBs, frequently relies on renal function, blood pressure regulation, and patient tolerability (Li et al., 2021; Journal of the American College of Cardiology, 2022). Research indicates that compliance with prescribed monitoring techniques, such as routine evaluation of serum creatinine and potassium levels, is essential for enhancing patient outcomes (McMurray et al., 2014). Clinicians are urged to implement a patient-centred approach, adjusting dosages based on individual responses and adapting to changing clinical circumstances. The BNF 2024 recommends that all patients with diabetic nephropathy, proteinuria, or confirmed microalbuminuria should be treated with ACEIs and ARBs (BNF, 2024). Lisinopril and Captopril are unique among ACE inhibitors as they are not prodrugs, making them appropriate for use in patients with hepatic impairment (Singh et al., 2025).

Pregnancy Considerations: These drugs are forbidden during pregnancy because of their teratogenic risks, requiring alternate therapeutic choices (American Journal of (Obstetrics & Gynaecology, 2020; Buawangpong et al., 2020). Studies showed teratogenic effects, such as renal dysgenesis, oligohydramnios, and, in severe cases, fetal death, mainly when used in the second and third trimesters. As a result, healthcare providers must discontinue ACEIs and ARBs in women who are planning to conceive or are already pregnant. Timely identification of pregnancy is essential to mitigate exposure, and regular pregnancy testing may be recommended for women of reproductive capacity who are undergoing these treatments (Countouris et al., 2025; Walfisch et al., 2011). In pregnancy, the use of ACE inhibitors is contraindicated during the second and third trimesters due to established risks of fetopathy. The risks associated with first-trimester exposure remain inadequately characterized. A significant correlation has been identified between exposure to ACE inhibitors during the first trimester and the occurrence of major cardiovascular and neurological malformations (Singh et al., 2025). Breastfeeding considerations: ACE inhibitors exhibit low bioavailability; however, they are metabolized into active metabolites that possess extended half-lives. Evidence suggests that minimal quantities of the parent drug and its metabolite are found in breast milk for other ACE inhibitors. Enalapril is frequently favored based on the extensive published data and minimal infant exposure. ACE inhibitors can be utilized with caution while breastfeeding. [31] ACE inhibitors are generally regarded as safe for breastfeeding mothers, with exceptions for cases of premature birth or renal failure in the infant (Singh et al., 2025).

Future Directions

Subsequent research will probably concentrate on broadening the therapeutic applications of ACEIs and ARBs in novel and evolving clinical scenarios (Journal of Clinical Hypertension, 2024; Schiffrin et al., 2020). Furthermore, current research seeks to elucidate the long-term comparative efficacy of ACEIs against ARBs, which will aid in the refinement of therapeutic guidelines and improve the personalized use of these medications (Packer et al., 2015).

Interpretation of Results

The analysis of the results underscores numerous critical aspects concerning the utilization of ACEIs and ARBs. Adherence to guidelines is essential, as contemporary practices frequently diverge from established standards. Numerous studies have identified deficiencies in monitoring and management, indicating that clinical practice frequently fails to meet guideline standards, especially with baseline monitoring and follow-up for patients taking ACEIs and ARBs. Factors affecting the suitability of commencement and management encompass patient-specific attributes, including renal function, comorbidities, and the risk of side consequences such as hyperkalaemia and renal impairment. These characteristics require personalized treatment approaches and underscore the significance of consistent biochemical monitoring to avert problems. To boost the suitability of ACEIs and ARBs in clinical practice, it is advised that healthcare practitioners bolster adherence to guidelines, particularly by underscoring the significance of thorough risk assessments, personalized treatment approaches, and consistent follow-up monitoring. By addressing these deficiencies, doctors can improve patient outcomes and reduce the likelihood of adverse events.

• A systematic study by Li et al. (2021) assessed the suitability of ACIEs and ARBs, highlighting the necessity for clarity regarding their comparative efficacy and safety. Singh et al. (2025) emphasised the difficulties in administering these drugs in clinical practice, hence underscoring the need for this scoping study.
• The ESC (2021) and recent publications (Circulation, 2023; Journal of Clinical Hypertension, 2024) contribute to ongoing discussions about their roles in managing heart failure and hypertension.
• The ESC 2024 and the ACC and AHA 2024 guidelines emphasize similar principles in managing cardiovascular conditions using ACIEs and ARBs while highlighting critical differences in their recommendations for specific patient populations.
• According to the 2024 ESC guidelines, initiation of ACEIs or ARBs should always begin with a low dose, followed by gradual titration to achieve therapeutic targets, with close monitoring of renal function and electrolyte levels, particularly in high-risk groups such as patients with diabetes or chronic kidney disease. In cases of heart failure with decreased ejection fraction (HFrEF), ACEIs are typically the chosen first-line therapy. Concurrently, ARBs provide an appropriate alternative for individuals who suffer from side symptoms, such as cough, associated with ACEIs. The guidelines advise against the use of combination therapy with both ACEIs and ARBs due to the increased risk of side effects such as hyperkalaemia and renal impairment. The guidelines emphasize the necessity of consistent follow-up, including annual evaluations of renal function and electrolytes, to guarantee the safety and efficacy of the medication (European Society of Cardiology, 2024).
• The 2024 ACC/AHA guidelines offer critical suggestions for using ACEIs and ARBs in treating cardiovascular disorders and prioritizing patient safety. It is recommended to initiate these drugs at low dosages, particularly in patients with heart failure or those at heightened cardiovascular risk, followed by incremental dose escalations. ACEIs are the primary treatment for heart failure with reduced ejection fraction, although angiotensin receptor blockers provide a suitable alternative for those who cannot tolerate ACEIs. The ACC/ AHA guidelines advise against the concomitant use of ACE inhibitors and ARBs due to the heightened risk of adverse consequences, including hyperkalaemia and deteriorating renal function. Consistent evaluation of renal function and electrolytes is essential after initiation, with recommendations for annual or more frequent long-term follow-up examinations based on the patient’s risk factors (American College of Cardiology, 2024; American Heart Association, 2024). Both guidelines emphasise a patient-centred approach, focusing on personalised treatment regimens, vigilant monitoring, and dosage adjustments to optimise therapeutic efficacy while minimising the likelihood of adverse effects.

Limitations include study design and outcome variability, insufficient data on specific patient populations or diseases, and biases. The diversity and variability in research methodologies may affect the generalizability of findings. Ultimately, papers published in languages other than English will be excluded, potentially disregarding relevant findings.

Strengths

We integrated extensive coverage and a wide-ranging reach, encompassing many sources and data from prominent clinical guidelines and governmental authorities. We employed a transparent and reproducible methodology, using a stringent search to identify all pertinent studies and minimise selection bias. The overall quality was examined to help readers assess the reliability and validity of the evidence and consider the robustness of the overall conclusions. An exhaustive review and analysis of recent research pertinent to behavioural change and clinical inertia in diabetes management encompassing a variety of interventions and techniques.

Conclusion

This review aims to consolidate the existing evidence about using ACEIs and ARBs to inform clinical decision-making. The evaluation of these medicines highlights their considerable clinical efficacy and safety in various settings. The results underscore the significance of personalized treatment strategies, especially when commencing these drugs at minimal doses and progressively adjusting them. Guidelines constantly recommend vigilant monitoring to enhance therapy outcomes, especially in high-risk groups. The review outlines current research domains focused on enhancing clinical techniques and addressing emerging issues, particularly in the areas of long-term outcomes and comparative effectiveness.

Recommendations

Healthcare practitioners must acquire comprehensive knowledge from prominent clinical recommendations and governmental authorities to provide these medications appropriately and successfully. Comprehensive recommendations must be developed to address the noted deficiencies. Subsequent research on patientspecific attributes and longitudinal studies will address information deficiencies, enhance therapeutic practices, and assess long-term results and the efficacy of medications.

Policy and Impact on Clinical Practice

Amendments to policy and the implementation of best practices are crucial for effectively and appropriately utilising these drugs. Implementing major clinical guidelines and adhering to recommendations from governmental agencies is crucial for using these medicines appropriately and avoiding harm. Medications must be tailored to individual patient needs, and an individualized approach requires attention to patient-specific factors such as comorbidities, drug interactions, and cardiovascular events, especially before initiation and during treatment. Clinicians should assess baseline renal function and electrolyte levels, particularly in high-risk patients with chronic kidney disease or diabetes. Furthermore, the combination of medications should generally be avoided.

Acknowledgements

We would appreciate the co-authors for Their Continuous Support, Cooperation, and Assistance.

Funding

This research was conducted without funding.

Availability of Data and Materials

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

Declarations

Ethics Approval and Consent to Participate: Not applicable.

Consent for Publication: Not applicable.

Competing Interests

The authors declare that they have no competing interests.

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