2.5.5 Drugs affecting the renin-angiotensin system

General guidance

• For the treatment of heart failure good evidence exists to support the use of ACE inhibitors to reduce mortality.
• Cough – troublesome cough is a well recognised adverse effect, however its frequency is often over quated – it probably effects up to 10-20% of all patients on an ACE inhibitor and occurs within the first eight weeks of treatment.

Sacubitril / valsartan (Entresto)

Sacubitril / valsartan (Entresto)

For adult patients for treatment of symptomatic chronic heart failure with reduced ejection fraction

See Dudley Health Economy guidance on implementation - click here

2.5.5.1 Angiotenisn- converting enzyme inhibitors

General guidance

• Hypertension: For Dudley Hypertension Pathway click here  or the Dudley Hypertension Clinic Reference Guide
• ACE inhibitors are particularly indicated for hypertension in diabetics with nephropathy.
• Heart failure: ACE inhibitors have a valuable role in all grades of heart failure, combined when appropriate with a diuretic and digoxin. It is important to ensure that the dose is optimised.
• Diabetic nepropathy: ACE inhibitors decrease the rate of decline in renal function.
• Myocardial infarction: ACE inhibitors are used in the immediate and long-term management of patients who have had a myocardial infarction, ramipril should be considered the agent of choice in this indication.
• Potassium supplements and potassium-sparing diuretics should be discontinued before introducing an ACE inhibitor because of the risk of hyperkalaemia. However, a low dose of spironolactone may be beneficial in severe heart failure and can be used with an ACE inhibitor provided the serum potassium is monitored carefully.
• Profound first-dose hypotension may occur when ACE inhibitors are introduced to patients with heart failure who are already taking a high dose of a loop diuretic (e.g. frusemide 80mg daily or more). Temporary withdrawal of the loop diuretic reduces the risk, but may cause severe rebound pulmonary oedema. The ACE inhibitor should therefore be started at very low dosage, with the patient recumbent. In other patients with heart failure ACE inhibitor therapy should be initiated in the community – concerns about first dose hypotension should not prevent these patients receiving appropriate therapy.
• Dry cough may affect 10-20% of patients treated with ACE-inhibitors and occurs within the first eight weeks of treatment.

Recommended drugs

Lisinopril £

Ramipril capsules £

Perindopril ££

2.5.5.2 Angiotensin- II receptor antagonists

General guidance 

• The Area Clinical Effectiveness Committee (ACE, formerly AMMC) agreed a verdict on the rational use of ARBs; this is that ARBs are approved for use second line when ACE-inhibitors are not tolerated or contraindicated.  Beyond this their role in the management of hypertension remains to be established.

• Angiotensin-II receptor antagonists should not be considered first line drugs for any indication.

Recommended drugs

Losartan £

Candesartan ££

Irbesartan (appoved for hypertension, diabetic nephropathy in type 2 diabetes) £££

Valsartan (approved for hypertension, post myocardiol infarction with LVF or LVSD) £££

2.5.5.3 Renin Inhibitors

General Guidance

For Dudley Hypertension Pathway click here

Renin inhibitors inhibit renin directly; renin converts angiotensinogen to angiotensin I. Aliskiren is licensed for the treatment of hypertension, either alone or in combination with other antihypertensives.

Recommended drugs

Aliskiren £££

Drug Traffic Light Key:

Green – On Formulary

Amber – Restricted use, see local guidelines      

Purple – Specialist use/initiation

Red – Non Formulary

Relative Costs Key (where indicated):

£££££ - high

£££ - moderate

£ - low