Why ACE inhibitors are the right choice if you want to provide ‘Better Care and Better Value’ to patients and the NHS Renin-angiotensin system (RAS) drugs include ACE (Angiotensin-converting enzyme) inhibitors, A2RAs (angiotensin-II receptor antagonists, also called angiotensin-receptor blockers [ARBs]) and the new direct renin inhibitor, aliskiren▼ (which is licensed only for use in hypertension). When choosing a RAS drug, as in any other therapeutic area, the decision should be guided by four factors: efficacy, safety, patient factors and cost.
Why ACE inhibitors first-line? EFFICACY
No evidence that A2RAs are more effective than ACE inhibitors for any indication
A2RAs cause cough in fewer patients than ACE inhibitors (absolute difference in discontinuation due to cough 3% in ONTARGET)
Concern that A2RAs may be less effective than ACE inhibitors in reducing some cardiovascular outcomes
Place in therapy of ACE inhibitors, A2RAs and combination therapy with an ACE inhibitor plus an A2RA in various indications ACE inhibitors A2RAs
ACE inhibitor plus A2RA
First-line RAS drug
No benefit, increased harm due to greater adverse drug reactions when compared with ACE inhibitor alone in ONTARGET
No difference in dosing regimens or monitoring requirements
First-line RAS drug
First-line RAS drug
No evidence that A2RAs are safer than ACE inhibitors
Generic ACE inhibitors are less expensive than A2RAs
Diabetes and CKD (Chronic kidney disease)
First-line RAS drug
But what about the cough? In all NICE guidance where RAS drugs are mentioned, A2RAs are reserved for patients where RAS drug is indicated, but an ACE inhibitor has to be discontinued because of an intolerable ACE inhibitor-induced cough. The current NICE heart failure guidance states that ACE inhibitor-induced cough rarely requires treatment discontinuation. In patients with heart failure, a cough might be caused by a symptom of pulmonary oedema. Other possible causes of cough should be considered before switching to an A2RA. In ONTARGET, 4.2% of patients in the ACE inhibitor (ramipril) group stopped treatment due to cough compared with 1.1% in the A2RA (telmisartan) group. This is an absolute difference of just 3.1% and indicates a number needed to harm (NNH) with ramipril of 32 over 56 months. This means 32 people need to be treated with telmisartan rather than ramipril for four and a half years to prevent one person having to stop treatment because of a cough.
PATIENT FACTOR Cough may not be as common with ACE inhibitors as many health professionals perceive
PATIENT FACTOR ACE inhibitors and A2RAs have similar monitoring requirements and both require dose titration
If ACE inhibitor discontinued due to ACE inhibitor-induced cough and RAS drug in particular indicated If ACE inhibitor discontinued due to ACE inhibitor-induced cough If ACE inhibitor discontinued due to ACE inhibitor-induced cough If ACE inhibitor discontinued due to ACE inhibitor-induced cough
Possibly a specialist option after ACE inhibitor and beta-blocker optimised Requires careful monitoring of renal function Not recommended in NICE post-MI guidance
No benefit, increased harm due to greater adverse drug reactions when compared with ACE inhibitor alone in ONTARGET Full NICE CKD guidance says no evidence to suggest increased effectiveness over ACE inhibitor alone Requires careful monitoring of renal function if specialists are using in high-risk renal patients
Generic ACE inhibitors are considerably less expensive than A2RAs
ACE inhibitors have a more robust evidence base than A2RAs for all indications
Patient factors other than cough • Commonly used ACE inhibitors and A2RAs are taken once or occasionally twice daily • Similar monitoring requirements (renal function)
• Identical potentially hazardous drug interactions: - Increased risk of hyperkalaemia with ciclosporin, potassium sparing diuretics, each other, and potassium salts - Increased hypotensive effect with diuretics - Reduced excretion of lithium
• Both ACE inhibitors and A2RAs contraindicated in pregnancy and breastfeeding • Drugs from both classes may need dose alteration, closer monitoring or avoidance in hepatic and/or renal impairment
NHS Better Care, Better Value (BCBV) Indicators “The NHS must demonstrate that it is making the most effective use it can of public money to deliver quality care.” NHS Institute for Innovation and Improvement, http://www.productivity.nhs.uk BCBV indicator-increase low cost prescribing of drugs affecting the renin-angiotensin system Defined as “the percentage of items written for ACE inhibitors (excluding combination products) as a percentage of the total volume of prescribing for drugs affecting the RAS (excluding combination products)”.
Angiotensin-converting enzyme inhibitors as a % of all Renin-angiotensin system drugs NHS Kirklees Q3 2009/10
Indicator (Items / Items ) PCT average Top quartile >73.89%
• ACE inhibitors are the first-line choice when a RAS drug is indicated - ACE inhibitors have a more robust evidence base than A2RAs for all indications in terms of evidence for efficacy, safety and most patient factors. • A2RAs are an alternative to ACE inhibitors if a RAS drug is indicated but an ACE inhibitor cannot be used because of an intolerable ACE inhibitorinduced cough - The percentage of people reporting cough with ACE inhibitors in randomized controlled trials (RCTs) is about 10%, and as low as 2% in observational, real world studies.
THE WHITEHOUSE CENTRE DR DUTT WEST YORKSHIRE URGENT CARE SERVICES SLAITHWAITE HEALTH CENTRE HONLEY SURGERY DR SINGH MELTHAM VILLAGE SURGERY THE GRANGE GROUP PRACTICE LIVERSEDGE MEDICAL CENTRE VICTORIA MEDICAL PRACTICE PADDOCK AND LONGWOOD FAMILY PRACTICE SCHOOL HOUSE PRACTICE LCD - KIRKLEES - OOH WESTBOURNE SURGERY DR BARNWELL AND PARTNERS SHEPLEY HEALTH CENTRE DR HANDA & PARTNER THORNTON LODGE SURGERY DALTON SURGERY RAVENSTHORPE HEALTH CENTRE DR TAYLOR & PARTNERS FOX CLECKHEATON HLTH CTR THE ALMONDBURY SURGERY ALBION STREET SURGERY DR JENNISON & PARTNERS SKELMANTHORPE FAMILY DOCTORS UNDERCLIFFE SURGERY MELTHAM GROUP PRACTICE FIELDHEAD SURGERY UNIVERSITY HEALTH CENTRE KIRKGATE SURGERY SCRIVINGS CLECKHEATON HLTH CTR DR BHUYAN BLACKBURN RD.MEDICAL CTR. THE JUNCTION SURGERY BATLEY HEALTH CENTRE SURGERY DR HARIHARAN & PARTNER DR CLAYDEN, SHAMSEE & ASSOCIATES DR WYBREW & PARTNER THE LINDLEY GROUP PRACT. DOCTOR LANE HEALTH CENTRE DR CHANDRA & PARTNERS THE ALBION MOUNT MEDICAL PRACTICE LOCKWOOD SURGERY DEARNE VALLEY HEALTH CENTRE CROFT HOUSE SURGERY MELTHAM ROAD SURGERY DR T UNNIKRISHNAN'S PRACTICE THE PADDOCK SURGERY DR BOULTON AND PARTNERS CHERRY TREE SURGERY KIRKBURTON HEALTH CENTRE WEST PARK SURGERY MARSDEN HEALTH CENTRE DR DAS & PARTNER THE WATERLOO PRACTICE THE NEW BREWERY LANE SURG DR HAMID AND PARTNERS HALIFAX ROAD SURGERY EIGHTLANDS SURGERY WELLINGTON HOUSE BROUGHTON HOUSE SURGERY SLAITHWAITE ROAD SURGERY DR GLENCROSS MOUNT PLEASANT MED CENTRE THE LINDLEY VILLAGE SURG. MARSH SURGERY SAVILE TOWN MEDICAL CTR. DR BUTT & PARTNER SAFEHAVEN DR REDDY & PARTNER WINDSOR MEDICAL CENTRE GROVE HOUSE SURGERY GREENSIDE SURGERY ST JOHN'S HOUSE BROOKROYD HOUSE DR GOWA
NHS Kirklees currently: 1. has the lowest prescribing rates of ACE inhibitors as a % of all drugs prescribed affecting the RAS in Yorkshire and the Humber Strategic Health Authority,
2. is below the England average of 71.23% 3. is ranked 130/153 out of the PCTs in England.
• Combination therapy with an A2RA plus an ACE inhibitor has a limited role and then only in certain conditions • Based on evidence, ACE inhibitors should comprise a higher proportion of RAS drug prescribing than is currently the case - Across primary care in England, only about 70% of RAS drug prescribing is for ACE inhibitors at the current time, with 30% for A2RAs. However, A2RAs account for 70% of the total spend on the RAS drugs. - A review of prescribing in this area could improve quality of care and reduce prescribing costs.
References: • MeReC Bulletin Volume 20, Number 2
• British National Formulary 59, March 2010
• Prescription Services NHS Business Services Authority/ePACT.net Ref: LJ3656