Northern Ireland Regional Prescribing Policy on Angiotensin Converting Enzyme (ACE) Inhibitors

Northern Ireland Regional Prescribing Policy on
Angiotensin Converting Enzyme (ACE) Inhibitors
and Angiotensin – II Receptor Antagonists
(A-IIRAs)
Guidance on choice of ACE Inhibitors and A-IIRAs in Primary and Secondary Care
This guideline on ACE inhibitors and A-IIRAs has been developed by an expert group to
recommend suitable first line agents for the treatment of common therapeutic indications.
The ACE inhibitors recommended by the expert group are:
• Lisinopril
• Perindopril
• Ramipril
Recommended choices for common therapeutic
areas suggested by the evidence base.
These represent suitable first line choices for the majority of clinical indications and are
supported by clinical trial data. The A-IIRAs should be reserved for patients who are truly
intolerant to ACE inhibitors in all of the therapeutic areas covered by this guidance (due to
the greater evidence base and outcome data for ACE inhibitors).
The A-IIRAs recommended by the expert group are:
• Candesartan
• Irbesartan
• Losartan
• Valsartan
Detailed information
Further information on the evidence base for these choices and additional material can be
found in the accompanying support document and at:
http.//www.dhsspsni.gov.uk/index/pas/pas-psip/pas-therapeutic_tendering.htm
Drug
Lisinopril
Perindopril
Ramipril
Starting
dose
10mg*
2mg
2.5mg
Hypertension/CKD
Target dose
Titrate as required
Titrate as required
Titrate as required
Candesartan
Irbesartan
Losartan
Valsartan
8mg
150mg#
50mg#
80mg
Titrate as required
Titrate as required
Titrate as required
Titrate as required
Note: Contraindications to ACE inhibitors / A-IIRAs include:
• Severe valvular stenosis • Pericardial constriction • Pericardial effusion • Pregnancy
Known CVD
Target dose
8mg
10mg
Heart Failure
Target dose
30mg
10mg
32mg
160mg bd
* Lower starting doses may be required in the presence of renal impairment or in patients with a
strongly activated renin-angiotensin-aldosterone system. Refer to the SPC for further information.
# In Chronic Kidney Disease (CKD), lower doses of irbesartan and losartan are available if appropriate.
A-IIRA option If patient cannot tolerate
ACE inhibitor
For patients requiring therapy for 2 (or more) disease areas, select a
drug recommended for both indications.
Hypertension
• Lisinopril
or
• Perindopril
or
• Ramipril
• Candesartan
or
• Losartan
or
• Valsartan
Known
Cardiovascular
Disease
• Perindopril
or
• Ramipril
• No major
outcome
data yet
Heart Failure
• Lisinopril
or
• Ramipril
• Candesartan
or
• Valsartan
Chronic
Kidney
Disease
• Lisinopril
or
• Ramipril
• Irbesartan*
• Losartan*
* evidence is in type II
diabetic nephropathy
or
There is clear evidence in diabetic nephropathy and non-diabetic chronic renal diseases that the
administration of ACE inhibitor or A-IIRA slows the progression of chronic renal failure, with the
greatest benefit in patients with higher degrees of proteinuria.
* Notes on initiating ACE inhibitor / A-IIRA in renal impairment can be found overleaf.
Northern Ireland Regional Prescribing Policy on Angiotensin Converting
Enzyme (ACE) Inhibitors and Angiotensin – II Receptor Antagonists (A-IIRAs)
Guidance on choice of ACE Inhibitors and A-IIRAs in Primary and Secondary Care
Information on Initiating ACE Inhibitors / A-IIRAs in Primary Care
The following information is a guide for General Practitioners on initiating and monitoring ACE / A-IIRAs
in primary care.
Before starting ACE inhibitors / A-IIRA, consider specialist advice if any of the following apply:
• eGFR < 30ml/min*
• Diuretic dose >80mg furosemide daily or bumetanide
2mg daily
• Sodium ≤130mmol/l
• Potassium >5.5mmol/l
• Persistent Systolic BP <90mmHg
• Known or suspected renal artery stenosis or aortic
stenosis
• History of angioneurotic oedema
Adverse effects:
Common adverse effects with ACE inhibitors and/or A-IIRAs are listed below along with advice on how
these may be appropriately managed.
Contra-indications to ACE inhibitor / A-IIRA therapy include:
Hypotension:
Cough:
• Severe valvular stenosis
• Pericardial effusion
• Asymptomatic low blood pressure - no change in
therapy required
• Symptomatic low blood pressure - consider stopping
or reducing other drugs. If no signs of fluid retention
consider reducing diuretics
• Consider other causes - respiratory disease
• Exclude pulmonary oedema
• If persistent and troublesome - Consider changing to
an A-IIRA
Renal Impairment
Hyperkalaemia
Declining renal function after initiating ACE inhibitor / AIIRA treatment is more likely in the elderly, patients with
volume depletion (on diuretics, GI losses), severe heart
failure, those on NSAIDs and those with or at risk of
diffuse atherosclerosis / renal artery stenosis:
For more detailed information please see the CREST
Hyperkalaemia Guidelines
http://www.crestni.org.uk/hyperkalaemia-booklet.pdf
• Pericardial constriction
• Pregnancy
STEP 1 - Review current drug therapy.
• Stop potassium-sparing diuretic#.
• Consider reducing diuretic dose.
• NSAIDs (inc. Cox-II selective) should be stopped if
possible.
STEP 2 - Initiate ACE inhibitor / A-IIRA & review within 2 weeks.
• Start with a low dose (see overleaf).
• Increase dose at weekly intervals.
• Monitor eGFR, creatinine, electrolytes within 2 weeks.
STEP 3 - Review after one month.
• Titrate dose of ACE inhibitor / A-IIRA.
• Assess any side effects & address any compliance
issues.
• Check need for ongoing diuretics.
• Check eGFR, creatinine, electrolytes.
STEP 4 - Review at 6mths & annually thereafter (or sooner if dose change or patient becomes
unwell - especially dehydration).
• Repeat eGFR, creatinine, electrolytes & BP as required.
Maintenance.
• Aim for target doses or highest tolerated dose.
Remember some ACE inhibitor is better than no ACE
inhibitor.
• Ask about S/E - cough, dizziness etc.
• Warn about drug interactions e.g. NSAIDs.
* Urea levels are not included in this guidance and have been replaced by creatinine and eGFR results.
# Aldosterone antagonists may be indicated concurrently with ACE inhibitor / A-IIRA treatment in
congestive heart failure and should be discontinued only upon specialist advice.
• An initial increase in serum creatinine (< 20%) is
common and requires no action if the patient
remains well and the creatinine / eGFR rise is stable.
• A rise in serum creatinine concentration of ≥ 20% or
fall of eGFR of > 15% during the first 2 months after
initiation of ACE inhibitor / A-IIRA treatment may be
an indication of underlying renal artery stenosis and
need for investigation.
• Increases in creatinine of between 20 - 30% (or eGFR
decrease of ~15 - 20%) from baseline may be
acceptable if they improve after reduction in diuretic
/ stopping NSAID. Reduce or stop diuretics if no signs
of fluid retention. Consider reducing ACE inhibitor / AIIRA dose especially if blood pressure is at or below
target.
• If creatinine increases by > 30% (or eGFR decreases
by > 20%) from baseline, nephrology referral is
indicated and the ACE inhibitor / A-IIRA should be
stopped.
• Hyperkalaemia is rare in patients with normal renal
function (eGFR > 60mls/min). See above.
• Hyperkalaemia is classified as mild (K+ 5.5 - 6.0),
moderate (K+ 6.1 - 6.9) or severe (K+ ≥ 7.0) or if ECG
changes or symptoms (muscle weakness or flaccid
paralysis palpitations, paresthesias) occur at ANY
level or serum potassium ≥ 5.5mmol/l especially if
associated with hypoxia.
• K+ 5 – 6mmol/l: If this level is an unexpected or
isolated finding repeat the sample without delay to
avoid haemolysis causing pseudohyperkalaemia. If
confirmed, this level is acceptable if the patient is
well, renal function is stable and drug therapy is
unchanged.
• K+ 6 – 7mmol/l: Stop K+ supplements, K+ sparing
diuretics and NSAIDs. Re-check within 24 hours. In
the absence of these drugs stop ACE inhibitor / AIIRA.
• K+ >7mmol/l: Urgent referral to hospital. NOTE:
urgent treatment is required if K+ is > 7mmol/l or
hyperkalaemia is accompanied by ECG changes.
This summary guide is accompanied by more detailed additional notes on the evidence for selected
agents and monitoring requirements.
http://www.dhsspsni.gov.uk/index/pas/pas-psip/pas-therapeutic_tendering.htm
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