Clinical Audit Article
Title of Audit:
Adherence to NICE guidelines for serum creatinine and serum potassium monitoring in
patients started on Angiotensin Converting Enzyme (ACE) Inhibitor or Angiotensin
Receptor Blocker (ARB).
Date of Report:
12th June 2024
Department/Speciality:
Cardiology Department in Bahria Town
International Hospital
Re-audit date:
Audit lead/Author:
Ibrahim
Job Title:
Internal Auditor
Key Stakeholders/
Contributors:
Dr. Ammar Nadeem
Medical Officer
Dr. Araj Siddiqui
Medical Officer
Dr. Khawar Saleem
Senior Medical Officer
Dr. Rabia
Medical Officer
Introduction:
Renin-angiotensin system blockade using ACE inhibitors (ACEI) and angiotensin receptor blockers (ARBs)
is a cornerstone in the treatment of hypertension, heart failure, diabetic microalbuminuria or
proteinuric renal diseases, and post-myocardial infarction care. However, some patients experience a
sudden decline in kidney function upon initiating these drugs, likely due to the antagonism of
angiotensin II-mediated efferent arteriolar constriction or impaired kidney excretion of potassium.
To assess the potential impact on kidney function, it is important to compare pre-initiation and postinitiation levels of serum creatinine and potassium. Discontinuation of treatment is recommended if
there is a rise in creatinine exceeding 30% above baseline or if hyperkalemia develops. However, it
remains unclear whether these recommendations are routinely followed in clinical practice.
The aim of this audit cycle was to to assess adherence to NICE guidelines for monitoring serum
creatinine and potassium levels following the initiation of ACE inhibitors (ACEI) or angiotensin receptor
blockers (ARBs).
NICE guidelines indicate that Angiotensin Converting Enzyme (ACE) Inhibitor or Angiotensin Receptor
Blocker (ARB) should be started with a low-dose and gradually be titrated upwards (usually every 2–4
weeks depending on the drug) until the person has reached the maximum advised or tolerated dose.
● Measure serum creatinine, estimated glomerular filtration rate (eGFR), and electrolytes before
starting treatment
○ If serum potassium is greater than 5 mmol/L, do not start treatment with an ACEinhibitor or ARB.
● Measure serum creatinine, eGFR, potassium, and blood pressure 1–2 weeks after each upward
titration.
○ If there is a decrease in eGFR or increase in serum creatinine after starting or increasing
the dose of renin-angiotensin system antagonist but it is less than 25% of baseline eGFR,
or 30% of baseline serum creatinine, repeat the test in 1–2 weeks. Do not modify the
renin-angiotensin system antagonist dose if the change in eGFR is less than 25% or the
change in serum creatinine is less than 30%.
○ If the change in baseline eGFR is 25% or more, or the change in baseline serum
creatinine is 30% or more, investigate for other causes of a deterioration in renal
function, such as volume depletion or concomitant nephrotoxic drugs such as
nonsteroidal anti-inflammatory drugs, and if no additional cause is found, stop the
renin-angiotensin system antagonist or reduce to a previously tolerated lower dose and
recheck levels in 5–7 days. Add an alternative antihypertensive medication if required.
○ If serum potassium is 5.0 mmol/L or above, investigate for other causes of
hyperkalaemia and treat accordingly. Stop or reduce the dose of potassium-sparing
diuretics (amiloride, triamterene, spironolactone) or nephrotoxic drugs if being given.
○ If serum potassium is persistently 5.0–5.9 mmol/L despite these measures, reduce the
dose of renin-angiotensin system antagonist to a previously tolerated lower dose and
recheck levels in 5–7 days.
○ Stop the renin-angiotensin system antagonist if serum potassium persists above 6
mmol/L, despite these measures.
Methodology:
This audit cycle was conducted in the cardiology department in Bahria Town International Hospital,
secondary care in Karachi, Pakistan.
A self-structured questionnaire form based on the NICE guidelines was designed and data of 50 cardiac
patients was included in the first audit cycle. The purpose of conducting the audit was explained to the
patients who were contacted through telephone and consent taken.
Data was collected on the following patient characteristics: Age, sex, any comorbidities such as presence
of chronic kidney disease (CKD), heart failure, myocardial infarction, hypertension, peripheral arterial
disease and diabetes.
The data was collected from the electronic health records and telephonic consultations with patients who
visited BTIH on inpatient/outpatient basis. It was then analyzed using the Microsoft Excel software.
The results were then presented in the form of a proper presentation to the members of Cardiology
Department, junior doctors and staff. A second cycle was then conducted after few days on 50 more
cardiac patients to assess compliance with the NICE guideline. Both the cycles were conducted from data
obtained from November 2023 till July 2024.
Results:
State the results. Start with total number (n =). Data may be presented visually (graphs, tables)
The results from both audits have been summarized in the following diagram (Figure 2).
Conclusion:
List key points that emerge from results
Several possible explanations exist for the divergence between clinical guideline
recommendations and the observed monitoring and response patterns in clinical practice, mainly
due to either Clinician Non-Adherence or Patient Non-Adherence. Clinicians may not
consistently order the recommended tests due to inconsistent guidelines for timing and frequency
of monitoring over time. On the other hand, even if instructed, patients may not adhere to
ordered tests, mainly due to financial restraints. This can be burdensome for patients, especially
those of the lower social economic status.
In conclusion, while most patients on ACEI/ARBs do not experience significant renal
impairment, the potential for substantial increases in creatinine levels reinforces the importance
of following clinical guidelines. Ensuring proper monitoring and patient counseling can help
mitigate risks and improve outcomes for high-risk individuals.
This study shows a significant improvement in all factors assessed in patients admitted with acute
pancreatitis, especially doubling the overall satisfaction of the patients with the information provided to
them after interventions in the form of patient information leaflets. This study concludes that patients should
be provided with all the necessary information according to their right to information as per GMC best
practice and NICE and Royal College of Nursing guidelines. Patient satisfaction is a crucial and frequently
used metric for assessing the quality of healthcare service. Effective education improves adherence to
therapy, which leads to better outcomes and promotes patient satisfaction. Patient health outcomes and
satisfaction can best be achieved by providing them with a patient information leaflet.
Recommendations:
REAUDIT:
In patients with both symptomatic and asymptomatic myocardial dysfunction, long-term
administration of ACE inhibitors alleviates CHF symptoms and reduces long-term morbidity and
mortality.
Angiotensin converting enzyme (ACE) inhibitors are now among the most commonly used
antihypertensive drugs. In addition to treating hypertension, they are also employed for longterm management of patients with congestive heart failure (CHF) and both diabetic and
nondiabetic nephropathies. Typically, ACE inhibitors improve renal blood flow (RBF) and sodium
excretion rates in CHF and help slow the progression of chronic renal disease. However, their use
can sometimes lead to "functional renal insufficiency" and/or hyperkalemia. This type of acute
renal failure (ARF) often arises shortly after starting ACE inhibitor therapy but can also occur after
months or years of use, even without previous side effects. ARF is more likely when renal perfusion
pressure drops significantly due to a decrease in mean arterial pressure (MAP) or when glomerular
filtration rate (GFR) heavily depends on angiotensin II (Ang II).
Renal function can acutely deteriorate when ACE inhibitor therapy is initiated or even in
patients on long-term ACE inhibitor therapy, especially those with CHF. ARF can occur
even if ACE inhibitor therapy has been stable for months or years. Assessing renal function
changes in CHF patients on chronic ACE inhibitor therapy can be challenging. Several
studies have examined the frequency of renal function changes in CHF patients treated
with ACE inhibitors. For instance, the CONSENSUS II trial (6090 patients) reported a 2.4%
incidence of a ≥0.5 mg/dL increase in serum creatinine. In the SOLVD studies, among
3379 patients assigned to enalapril and 3379 to placebo, decreased renal function,
defined as a rise in serum creatinine of ≥0.5 mg/dL from baseline, occurred in 16% of the
enalapril group versus 12% of the placebo group. Multivariate analysis indicated that
older age, diuretic therapy, and diabetes were associated with decreased renal function,
while β-blocker therapy and higher ejection fraction were protective.
ARF in this context often involves one or more of four mechanisms:
MAP Reduction: If MAP falls to levels that cannot sustain renal perfusion or
significantly activate renal sympathetic nerves, ARF will ensue with ACE inhibitor therapy.
Volume Depletion: ACE inhibitors often cause ARF in patients who are volumedepleted from diuretic therapy.
Patients whose serum creatinine increased with ACE inhibitors typically had higher
diuretic doses and lower ventricular pressures
Renal Artery Stenosis: ACE inhibitors may induce ARF in patients with high-grade
bilateral renal artery stenosis, stenosis of a dominant or single kidney,
Concurrent Vasoconstrictor Agents: ACE inhibitors may precipitate ARF in patients
taking vasoconstrictors such as NSAIDs or cyclosporine.
Patients with chronic renal insufficiency are at a higher risk for ACE inhibitor-induced
ARF due to adaptive changes that maintain GFR, including hyperfiltration. ACE inhibitors
reverse this hyperfiltration, causing an initial GFR drop and rises in blood urea nitrogen
and serum creatinine, which indicate the drugs' desired effects. There is no specific
serum creatinine level that contraindicates ACE inhibitor use, and a 10% to 20% increase
in serum creatinine is expected upon initiation, typically stabilizing or improving due to
the renoprotective effects of long-term ACE inhibitor use.
Management and Monitoring of ACE Inhibitors to Mitigate ARF Risk
To mitigate the risk of acute renal failure (ARF) in patients on ACE inhibitors, especially
those with chronic heart failure (CHF), careful monitoring is crucial. Patients prone to
ARF can be identified early with judicious monitoring, avoiding the need to withhold
ACE inhibitor therapy due to concerns about renal deterioration.

Baseline and Follow-up Testing: Serum creatinine and electrolyte levels should be evaluated
before starting ACE inhibitor therapy and again one week after initiation. More frequent testing
(e.g., within a few days) is not typically necessary unless there is sustained oliguria or a
significant decrease in blood pressure.
Hyperkalemia in Patients Treated with ACE Inhibitors
Hyperkalemia is a relatively common issue in patients with chronic heart failure (CHF) or
uremia who are treated with ACE inhibitors. However, significant increases in plasma
potassium are usually modest, with severe hyperkalemia being uncommon.
Mechanism of Hyperkalemia
ACE inhibitors can lead to hyperkalemia by:


Reducing Plasma Aldosterone Levels: This reduces urinary potassium excretion, which can
increase plasma potassium levels .
Diuretic Coadministration: Patients treated with ACE inhibitors often receive diuretics, which
usually help mitigate the risk of severe hyperkalemia by offsetting hypokalemia that might
otherwise occur with diuretic therapy.
Practical Recommendations




Initial Assessment: Evaluate baseline serum creatinine and potassium levels before starting ACE
inhibitors.
Follow-up Testing: Monitor serum potassium and creatinine levels 1 week after initiating
therapy and periodically thereafter, adjusting the frequency based on the patient's risk profile
and clinical stability.
Patient Education: Inform patients about the signs and symptoms of hyperkalemia (e.g., muscle
weakness, fatigue, palpitations) and instruct them to report any such symptoms promptly.
Medication Review: Regularly review the patient’s medications to identify and manage
potential interactions that could increase the risk of hyperkalemia.
By adhering to these monitoring and management strategies, healthcare providers can
effectively mitigate the risk of hyperkalemia in patients treated with ACE inhibitors while
still benefiting from their therapeutic effects.
MAIN ARTICLE:
Abstract
Objectives: This study aims to assess adherence to guidelines for monitoring serum creatinine
and potassium levels and discontinuation criteria following the initiation of ACE inhibitors
(ACEI) or angiotensin receptor blockers (ARBs). It also investigates whether high-risk patients
receive appropriate monitoring.
Design: This is a cohort study based on general practice, utilizing electronic health records from
the UK Clinical Practice Research Datalink and Hospital Episode Statistics.
Setting: The study was conducted in UK primary care between 2004 and 2014.
Subjects: The study included 223,814 new users of ACEIs or ARBs.
Main Outcome Measures: The primary measures were the proportion of patients with renal
function monitoring before and after starting ACEI/ARB therapy, instances of a creatinine
increase of ≥30% or potassium levels >6 mmol/L at the first follow-up, and the discontinuation
of treatment after such changes. Logistic regression models were used to analyze patient
characteristics associated with these biochemical changes and follow-up monitoring within the
recommended 2 weeks after treatment initiation.
Results: Ten percent of patients had neither baseline nor follow-up monitoring of creatinine
within 12 months before and 2 months after initiating ACEI/ARB therapy. Twenty-eight percent
had only baseline monitoring, 15% had only follow-up monitoring, and 47% had both baseline
and follow-up monitoring. The median time between the most recent baseline monitoring and
drug initiation was 40 days (IQR 12–125 days). Thirty-four percent of patients had baseline
creatinine monitoring within one month before starting therapy, but fewer than 10% had the
recommended follow-up test recorded within two weeks. Among patients who experienced a
creatinine increase of ≥30% (n=567, 1.2%) or potassium levels >6 mmol/L (n=191, 0.4%), 80%
continued treatment. Despite being at high risk of a ≥30% increase in creatinine after ACEI/ARB
initiation, patients with prior myocardial infarction, hypertension, or baseline potassium >5
mmol/L were not monitored more frequently.
Conclusions: Only one-tenth of patients initiating ACEI/ARB therapy received the guidelinerecommended creatinine monitoring. Additionally, the majority of patients who met the postinitiation discontinuation criteria for creatinine and potassium increases continued treatment.
Introduction
Renin-angiotensin system blockade using ACE inhibitors (ACEI) and angiotensin receptor
blockers (ARBs) is a cornerstone in the treatment of hypertension, heart failure, diabetic
microalbuminuria or proteinuric renal diseases, and post-myocardial infarction care. However,
some patients experience a sudden decline in kidney function upon initiating these drugs, likely
due to the antagonism of angiotensin II-mediated efferent arteriolar constriction or impaired
kidney excretion of potassium.
To assess the potential impact on kidney function, it is important to compare pre-initiation and
post-initiation levels of serum creatinine and potassium. Discontinuation of treatment is
recommended if there is a rise in creatinine exceeding 30% above baseline or if hyperkalemia
develops. However, it remains unclear whether these recommendations are routinely followed in
clinical practice.
Although a few studies have compared baseline and follow-up monitoring results, large studies
using contemporary data with reference to current guidelines are lacking. Additionally, it is
unknown whether a patient’s individual risk of renal impairment influences their likelihood of
being monitored. Therefore, we examined adherence to guidelines for creatinine and potassium
monitoring and treatment discontinuation following ACEI/ARB initiation in UK primary care,
and whether patients are monitored according to their individual risk profiles.
Methods
Data Sources: We utilized data from the UK’s Clinical Practice Research Datalink (CPRD)
linked to hospital records from the Hospital Episode Statistics (HES) database. The CPRD
database contains comprehensive primary care electronic health records. The information
recorded in this database includes demographics such as sex, year of birth, and the location of the
general practice, as well as medical diagnoses (based on ‘Read’ codes), drug prescriptions, and
various routine laboratory test results. HES records cover all hospital admissions for patients covered
by the National Health Service (NHS) who receive treatment either from English NHS trusts or
independent providers.
Monitoring Guidelines
Consistent with other international guidelines, the National Institute for Health and Care
Excellence (NICE) recommends baseline testing of creatinine when initiating ACEI/ARB
therapy in patients with hypertension, heart failure, myocardial infarction, or chronic kidney
disease (CKD). The specific time interval for baseline testing is not detailed in these guidelines.
For patients with heart failure, myocardial infarction, and CKD, NICE recommends follow-up
monitoring within 2 weeks of treatment initiation and at least annually thereafter for those with
myocardial infarction.
Additionally, a baseline assessment and follow-up test within 2 weeks are recommended by the
UK Renal Association and the frequently used online resource General Practice (GP) Notebook.
GP Notebook further suggests monitoring at 1, 3, 6, and 12 months after the initial follow-up
test. Furthermore, NICE advises against initiating ACEI/ARBs in patients with a baseline
potassium level greater than 5 mmol/L.
Patient Characteristics
We collected data on the following patient characteristics: age, sex, calendar period of
ACEI/ARB initiation (2004–2008 and 2010–2014), socioeconomic status (quintiles of the 2004
index of multiple deprivation scores), lifestyle factors (smoking, alcohol intake, and body mass
index), baseline potassium level (≤5 or >5 mmol/L), presence of chronic kidney disease (CKD),
cardiovascular comorbidities (including heart failure, myocardial infarction, hypertension,
peripheral arterial disease, and arrhythmia), and diabetes.
Statistical Analysis
We described ACEI/ARB users according to patient characteristics, both overall and based on
their creatinine monitoring status (no baseline or follow-up monitoring, baseline only, follow-up
only, and both baseline and follow-up monitoring). Baseline monitoring was defined as a test
performed on the date of drug initiation or within either 12 months before (wide interval) or 1
month before initiation (ideal interval). To align with the recommended post-initiation
monitoring interval from previous trial data, we considered only follow-up monitoring within the
first 2 months after drug initiation.
We calculated the proportion of new users who had baseline and follow-up monitoring within 1,
3, and 12 months before drug initiation and within 2 weeks, 1 month, and 2 months after
initiation. We also computed the proportion of persons with both baseline and initial follow-up
monitoring within the guideline-recommended interval of 2 weeks following drug initiation.
For continuing users, we examined adherence to stricter guideline recommendations for ongoing
monitoring (i.e., monitoring within 1, 3, 6, and 12 months after the first retest). Continuation was
defined as ACEI/ARB use beyond 30 days following the monitoring date. The end date of each
prescription was calculated by adding the prescription duration (total number of tablets
prescribed divided by the specified number of tablets per day) to the prescription date. We
allowed for a 30-day gap between the end date of one prescription and the start of the next
consecutive prescription to identify continuous courses of therapy.
In sensitivity analyses, we repeated the analyses by: (1) extending the follow-up window for the
first follow-up monitoring from 2 to 3 weeks to account for minor delays; (2) including only the
most recent calendar period (2009–2014) to account for temporal changes in data completeness
and quality of care; (3) excluding patients with a hospital admission or discharge date within 1
month before or after their first ACEI/ARB prescription, to account for drug initiation and
subsequent renal function tests occurring in the hospital; (4) focusing on specific patient
subgroups (heart failure, myocardial infarction, hypertension, CKD (eGFR <60 mL/min/1.73
m²), peripheral arterial disease, and diabetes); and (5) defining drug use continuation as
ACEI/ARB use beyond 90 days (instead of 30 days) after the first retest date.
Using the subcohort of patients with both baseline and follow-up monitoring, we calculated the
proportion of patients with creatinine increases ≥30% or potassium levels >6 mmol/L at the first
follow-up monitoring within 2 months after initiation, and the proportion of patients continuing
treatment despite these contraindications.
We fitted a logistic regression model to identify patient characteristics associated with a severe
decline in renal function (creatinine increase ≥30% or potassium level >6 mmol/L) and
compared these characteristics with those associated with receiving post-initiation follow-up
monitoring within 2 weeks. The model included age, sex, CKD stage, cardiovascular
comorbidities, diabetes, and baseline potassium level (>5 vs ≤5 mmol/L). In three additional
model-based sensitivity analyses, we repeated the analyses by: (1) excluding patients with a
recent hospitalization; (2) omitting baseline potassium from the model to examine potential
overfitting when both baseline potassium and CKD stage were included; and (3) additionally
adjusting for ethnicity.
All analyses were performed using the STATA 14 statistical software package.
Results
Serum Creatinine Monitoring Before and After ACEI/ARB Initiation
We identified 223,814 new users of ACEI/ARB. These patients were categorized into four
groups based on their creatinine monitoring status:




21,411 (10%) had no baseline or follow-up creatinine tests within 12 months before and 2
months after treatment initiation.
63,359 (28%) had only a baseline test.
33,185 (15%) had only follow-up tests.
105,859 (47%) had both baseline and follow-up tests.
Discussion


Only one-tenth of patients initiating ACEI/ARBs in UK primary care appear to receive
the guideline-recommended creatinine monitoring. Additionally, one in 15 patients
started ACEI/ARBs despite having a baseline potassium level above the recommended
threshold, which was identified as a strong predictor for severe post-initiation
hyperkalemia. Among the monitored patients, almost 1.5% experienced a creatinine
increase of ≥30% or a potassium level >6 mmol/L. Despite guideline recommendations to
discontinue therapy under these conditions, most patients did not stop treatment.
Patients with prior myocardial infarction, hypertension, or a high baseline potassium
level were at a higher risk of a sudden decline in kidney function following ACEI/ARB
initiation. However, there was no evidence that these high-risk patient groups received
more frequent or timely monitoring.
Clinical Relevance
Several possible explanations exist for the divergence between clinical guideline
recommendations and the observed monitoring and response patterns in clinical practice.
Clinician Non-Adherence: Clinicians may not consistently order the recommended tests due to
inconsistent guidelines for timing and frequency of monitoring over time. Guidelines are often
consensus-based rather than evidence-based and may not be tailored to high-risk patients, such as
those with CKD and heart failure. Although follow-up monitoring correlated well with the risk
of renal impairment after ACEI/ARB initiation for most patient groups, this was not observed for
patients with myocardial infarction or high pre-initiation potassium levels.
Patient Non-Adherence: Patients may not adhere to ordered tests, particularly in UK primary
care where blood samples are taken in phlebotomy clinics that require a separate visit. This can
be burdensome for patients, and GPs lack direct economic incentives to ensure tests are
completed.
Lack of Evidence for Clinical Importance and Cost-Effectiveness: There may be a perception
that monitoring is not critical due to the rarity of ACEI/ARB-induced renal impairment in
clinical trials, even among patients with multiple risk factors for atherosclerotic renal artery
stenosis. However, our data suggest that the risks in real-world practice may be higher.
Additionally, previous research has indicated that potassium monitoring in high-risk patients
with CKD and diabetes can reduce serious hyperkalemia-associated adverse events.
The extent to which an initial creatinine increase of ≥30% translates into adverse long-term
outcomes in real-world patients remains to be clarified in future studies. This underscores the
need for more robust evidence to inform guidelines and ensure they reflect the realities of
clinical practice.
Generalisability, Implications, and Conclusions
The majority of patients initiating treatment with ACEI/ARBs experience only minor changes in
renal function. However, substantial increases in creatinine levels after ACEI/ARB initiation
may not be as rare as previously suggested, highlighting the need for adherence to clinical
guidelines for both pre-initiation and post-initiation monitoring. The post-initiation creatinine
increase and potassium levels used in this study are widely recognized cut-off levels, making the
results applicable internationally. The comparison with previous literature confirms that the lack
of systematic monitoring is not exclusive to the UK.
A particularly concerning finding is that even when appropriate monitoring was performed,
severe renal impairment rarely led to treatment discontinuation. This underscores the need for
better adherence to guidelines and highlights the importance of individual patient counseling to
ensure that those at highest risk are closely monitored. More research is needed to determine the
prognostic significance of the changes in renal function observed in this study.
In conclusion, while most patients on ACEI/ARBs do not experience significant renal
impairment, the potential for substantial increases in creatinine levels reinforces the importance
of following clinical guidelines. Ensuring proper monitoring and patient counseling can help
mitigate risks and improve outcomes for high-risk individuals.