Renin Angiotensin Drugs (RAD) – The case for ACE inhibitors
Background
 There are 11 different Angiotensin Converting Enzyme Inhibitors (ACEIs) and 7 different Angiotensin II
Receptor Blockers (A2RBs) with significant differences in price between the two groups. Most ACEIs
are off patent and are considerably cheaper, of the A2RBs Losartan is off patent March 2010 and is
now more price competitive with the cheapest patented A2RB Candesartan.
 Currently A2RBs account for 30% of the RAD items prescribed nationally but is 70% of the costs. The
minimum cost saving is in excess of £100 per patient switched
 ACE inhibitors and A2RBs are licensed for a range of indications, including hypertension, cardiac
failure, renal complications of Diabetes, CKD and Post MI. There is no evidence A2RBs are superior to
ACE inhibitors, indeed ACE inhibitors have much stronger evidence of positive outcomes and
secondary end points than ARBs
 Data indicates that considerable cost savings can be made from reviewing prescribing to ensure the
most cost effective medication is used without adversely affecting patient care. This is not a simple
switch and requires an informed decision, patient engagement and careful monitoring.
 There is limited evidence that combination of ACEI plus A2RB is beneficial in heart failure only. This is
more usually specialist initiated and should be reviewed regularly 1
Licensed indications
Hypertension
Heart Failure
Diabetic
Nephropathy
MI Secondary
Prevention
Angiotensin converting enzyme inhibitors
Lisinopril / Captopril
Cilazapril / Enalapril / Fosinopril /
Quinalapril
Ramipril / Perindopril
Imidapril/ Trandolapril / Moexipril
Angiotensin II receptor antagonists
Candesartan
Losartan / Irbesartan
Olmesartan/ Telmisartan / Eprosartan
Valsartan
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Dose Comparison Chart
This is not a dose equivalence chart and should be regarded as a guide not a recipe. There is no published
data on switching and the approach should be pragmatic based on knowledge of the individual patient.
Drug
(£ per 28)
Low dose
Usual initiation dose
Enalapril
2.5mg (1.29)
5mg (1.16)
Lisinopril
2.5 – 5mg (1.001.15)
2mg (2.29)
Perindopril
*5-10mg (1.15)
Usual maintenance
dose(s)
10 - 20mg
(1.26-1.39)
10 - 20mg (1.15-1.39)
Max dose
40mg
80mg
4mg (2.38)
4 - 8mg (2.38-2.45)
8mg
Ramipril
1.25mg (1.17)
1.25 - 2.5mg (1.17-1.26)
5mg (1.35)
10mg (1.59)
Candesartan
2 – 4mg (13.67-9.25)
8mg (9.98)
8mg (9.98)
32mg 16.13)
Eprosartan
300mg (7.31)
600mg (14.31)
600mg (14.31)
800mg (16.54)
Irbesartan
75mg (9.69)
150mg (11.84)
150 - 300mg (11.84-15.93)
300mg (15.93)
Losartan
25mg (16.18)
50mg (12.80)
50 - 100mg (12.80-16.18)
100mg (16.18)
Olmesartan
Information not available
10mg (10.95)
10 – 20mg (10.95-12.95)
40mg (17.50)
Telmisartan
20mg (8.00)
40mg (12.50)
40 -80mg (12.50-17.00)
80mg (17.00)
Valsartan
40mg (13.97)
80mg (13.97)
80-160mg (13.97-18.41)
160 (18.41)
*If a thiazide is in use concurrently the dose of ACEI used may need to be reduced
Action Plan
Suggested
process
Identify all
patients on
A2RBs and
ACEI
Identify all
patients on
ARB2
Then identify
those
1. who have
never
had an
ACEI
Actions required and Rationale
Agreement By
When
whom
Review each case to ensure use is appropriate in light of
current guidance on lack of benefit in any condition except
heart failure
Invite any patients who are non concordant to attend for
review with a view to engagement and assessment of
need, if re initiating ensure the most appropriate drug e.g.
ACEI is selected
Review each patient with a view to exclude patients with
drug interaction or where switching would pose an
unjustifiable risk. For the remainder implement a managed
switch to formulary ACEI and ensure appropriate
monitoring/ dose titration.
2. who have Review drug choice. For patients with hypertension for
cough
recorded
as ADR
3. who are
not on a
formulary
ARB2
Identify all
patients on
ACEI
Audit
effectiveness
of the
programme
whom an ACE was 1st choice but suffered intractable
cough, is an A2RB the right drug. Consider if a thiazide or
Ca channel blocker could be used. Age may be relevant if
the patient is now over 55.
Review drug choice in light of current formulary advice. If
appropriate switch to a more cost effective A2RB
Invite any patients who are non concordant to attend for
review with a view to engagement and assessment of
need; if re initiating ensure the most appropriate ACEI is
selected.
Review drug choice for any patient not on a formulary
ACEI. Ensure ramipril is prescribed as caps and
perindopril as the erbutamine salt
Data collection and review
A template is available from the NPC
Exclusion criteria for switching
 Recorded / validated adverse reaction to ACEI which resolved on stopping and did not occur on
ARB2
 Patients whose clinical condition is unstable and change could result in serious adverse effects/
hospital admission.
So what about cough?
In trials a low percentage discontinue ACEI as a
result of intractable cough (2-10%). Not all coughs
require that the ACEI be stopped and the cough
does not always resolve on an A2RB as cough is a
common symptom in patients with heart failure or
who smoke. The absolute incidence for the
ONTARGET trial indicated a difference of just 3.1%
between ACEI and A2RB. Or put it another way if
100 people take an A2RB instead of an ACEI only
3 will avoid having to stop the medication because
of a cough and another one will stop whether they
had the A2RB or an ACEI.