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Unless contraindicated, oral anticoagulation with warfarin (target international normalised ratio [INR] 2.5) is the antithrombotic treatment of choice in patients with atrial fibrillation (AF) at high risk of stroke. Antiplatelet therapy with aspirin (75–300mg daily) is appropriate for those at low risk.¹ The Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W) study² was an open-label, randomised controlled study with blinded assessment of outcomes. It compared clopidogrel plus aspirin (75mg/75–150mg daily) with warfarin (target INR 2.0–3.0) in patients with AF (n=6,706) at moderate to high risk of stroke. The study was stopped early after a median follow-up of 15 months when it was found that clopidogrel plus aspirin was associated with a significantly greater risk of major cardiovascular (CV) events and bleeding compared with warfarin.²

The incidence of the primary outcome (stroke, non-CNS systemic embolus, myocardial infarction or vascular death) was 7.0% with clopidogrel plus aspirin and 4.9% with warfarin (number needed to harm [NNH] 47; relative risk [RR] 1.44, 95%CI 1.18–1.76, P=0.0003). The incidence of stroke was 3.00% with clopidogrel plus aspirin and 1.75% with warfarin (NNH=80; RR 1.72, 95%CI 1.24–2.37, P=0.001). There was no difference in total mortality between groups (4.8% clopidogrel plus aspirin, 4.7% warfarin). The incidence of bleeding was significantly greater with clopidogrel plus aspirin compared with warfarin (19.3% vs. 16.5%; NNH 35; RR=1.21, 95% CI 1.08–1.35, P=0.001). However, the incidence of major bleeding was similar (3.0% clopidogrel plus aspirin, 2.8% warfarin). Target INR was achieved 64% of the time in patients on warfarin: 21% of the time it was below 2.0 and 15% of the time it was above 3.0.²

ACTIVE-W supports the use of warfarin in patients with AF who are at high risk of stroke, according to the NICE guideline.¹ Clopidogrel plus aspirin is not a suitable alternative in these patients. Furthermore, there is currently no clinical evidence to support the use of clopidogrel alone, or clopidogrel plus aspirin, as an alternative to aspirin alone for those patients with AF who are at low risk of stroke, or where warfarin is contraindicated.

ACTIVE-W adds to the evidence from other studies (e.g. CURE,³ MATCH,⁴ CHARISMA⁵) that, with prolonged use, the benefits of clopidogrel plus aspirin may be outweighed by an increased risk of bleeding. This combination should only be considered for conditions where it has been established that the benefits outweigh the increased risk of bleeding, and then for only a limited time (e.g. a year following non-ST-segment-elevation acute coronary syndrome⁶).

National Institute for Health and Clinical Excellence. NICE Clinical Guideline 36. Atrial fibrillation: the management of atrial fibrillation. June 2006. Accessed from www.nice.org.uk on 07/08/06
The ACTIVE Writing Group on behalf of the ACTIVE investigators. Lancet 2006;367:1903–12
The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial investigators. N Engl J Med 2001;345:494–502
Diener H-C, Bogousslavsky J, Brass LM, et al. Lancet 2004;364:331–7
Bhatt DL, Fox KAA, Hacke W, et al. N Engl J Med 2006;354:1706–17
National Institute for Health and Clinical Excellence. Technology Appraisal Guidance 80. Clopidogrel in the treatment of non-ST-segment-elevation acute coronary syndrome. June 2004. Accessed from www.nice.org.uk on 31/08/06

There are now two beclometasone dipropionate CFC-free pressurised metered dose inhalers (pMDI) on the market in the UK: Qvar (Ivax Pharmaceuticals Ltd) and a new product, Clenil Modulite▼ (Trinity-Chiesi Pharmaceuticals Ltd). These two products are not equipotent.

The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that when the prescriber wishes a patient to have a CFC-free formulation of beclometasone dipropionate they should prescribe the product by brand name.¹ Pharmacists receiving a generic prescription for a beclometasone dipropionate pMDI must establish whether a CFC-free product is required and, if so, which of the two available branded products should be dispensed.¹ Clenil Modulite should be prescribed at the same dose as the currently available CFC-containing beclometasone dipropionate pMDIs.^1,2 Qvar has a 2 to 2.5 fold greater potency than these and should be prescribed at a lower dose.^1,3 Clenil Modulite is authorised for use in children (no age restrictions);^1,2 Qvar is not authorised for use in children 12 years of age and younger.^1,3

A number of changes are being introduced this year for the safe management of controlled drugs (CDs). In June and September 2006, further amendments to the Misuse of Drugs Regulations 2001 were announced. (These are in addition to those made in November 2005, see MeReC Extra No. 20, January 2006.) The main changes are outlined in the panel. Further changes planned for the inspection and monitoring of CDs are likely to come into force by the end of 2006. The Department of Health and Royal Pharmaceutical Society have useful documents on their websites (www.dh.gov.uk/PolicyAndGuidance/MedicinesPharmacyAndIndustry/Prescriptions/ControlledDrugs/fs/en and www.rpsgb.org/pdfs/cdmanagechguid.pdf).


Recent changes to CD requirements ^1,2
The introduction of a new private prescription form (FP10PCD) for schedule 2 and 3 CDs dispensed in the community (stocks are available through PCTs). There was a legal requirement to use these forms from 7th July 2006 in England, and for them to contain a private CD prescriber identification number issued by the Prescription Pricing Division of the NHS Business Services Authority. Each doctor has a unique number, whereas dentists have a number per PCT area.³ From 7th July 2006, all prescriptions for schedule 2, 3 and 4 CDs are legally valid for 28 days only. From 7th July 2006, there was a legal requirement to ascertain if a person collecting a schedule 2 CD is the patient, patient representative or health professional acting on behalf of the patient, and, from January 2008, to record this information in the CD Register. The new FP10PCD and new stocks of FP10 prescriptions will include an additional declaration on the back for the patient/representative to sign on collection. It is good practice to ensure this is completed for the collection of schedule 2 and 3 CDs. A good practice recommendation that prescriptions for schedule 2, 3 and 4 CDs be limited to up to 30 days supply. The CD register can be used to record additional information, e.g. running balances and prescriber identification numbers.

The NPC publication, 'A guide to good practice in the management of controlled drugs in primary care (England)' is also being updated and a full second edition will be available on the NPC website towards the end of September (www.npc.co.uk/background_for_cd.htm).

Department of Health. Safer management of controlled drugs (CDs): private CD prescriptions and other changes to the prescribing and dispensing of controlled drugs (CDs). Guidance for implementation. Gateway Reference: 6820. June 2006 (Final guidance)
Department of Health. Safer management of controlled drugs (CDs): changes to record-keeping requirements. Guidance for implementation. Gateway Reference: 6819. June 2006 (Interim guidance). Final guidance to be available in September 2006
Department of Health. Private controlled drugs prescriptions and dental prescribing. 31 May 2006

Smoking is the leading cause of preventable morbidity and premature death in England. Prevalence remains very high in certain groups including 20–34 year olds, members of some minority ethnic groups and those from lower socioeconomic groups.¹ The first public health intervention guidance was issued by NICE in March 2006.¹ This addresses how professionals, both within and outside the NHS, can most effectively use brief interventions and referral to specialist services to help people stop smoking.

NICE recommends that GPs should take the opportunity to advise all patients who smoke to quit when they attend a consultation, where appropriate. Those who want to stop should be offered a referral to an intensive support service, e.g. NHS Stop Smoking Services.¹ The Quality and Outcomes Framework of the General Medical Services contract awards points for recording patients' smoking status and providing cessation advice or referrals. NICE also highlights the role of other health professionals, e.g. nurses and pharmacists, and again recommends they refer people who smoke to an intensive support service.¹ If individuals are unwilling or unable to accept the referral, they should be offered drug treatment and additional support by practitioners with suitable training. Drug treatment should be in line with NICE technology appraisal guidance No. 39 (2002).^1,2 Full details of the new public health intervention guidance are available at www.nice.org.uk.

NICE public health programme guidance on smoking cessation is due in August 2007. Within this guidance NICE technology appraisal No. 39 will be updated.

National Institute for Health and Clinical Excellence. Public Health Intervention Guidance No.1. Brief interventions and referral for smoking cessation in primary care and other settings. March 2006. Accessed from www.nice.org.uk on 24/08/06
National Institute for Clinical Excellence. Technology Appraisal Guidance No.39. Guidance on the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation. March 2002. Accessed from www.nice.org.uk on 24/08/06
Sowerby Centre for Health Informatics at Newcastle. PRODIGY guidance: Smoking Cessation. February 2006. Accessed from www.prodigy.nhs.uk on 24/08/06
Duff G. New advice on use of nicotine replacement therapy (NRT): wider access in at-risk populations. Healthcare professional letter. December 2005. Accessed from www.mhra.gov.uk on 24/08/06
National Institute for Health and Clinical Excellence, Royal Pharmaceutical Society of Great Britain, PharmacyHealthLink. Helping smokers to stop: advice for pharmacists in England. August 2005. Accessed from www.publichealth.nice.org.uk on 24/08/06

The National Institute for Health and Clinical Excellence (NICE) is associated with MeReC Publications published by the NPC through a funding contract. This arrangement provides NICE with the ability to secure value for money in the use of NHS funds invested in its work and enables it to influence topic selection, methodology and dissemination practice. NICE considers the work of this organisation to be of value to the NHS in England and Wales and recommends that it be used to inform decisions on service organisation and delivery. This publication represents the views of the authors and not necessarily those of the Institute.

NPC materials may be downloaded / copied freely by people employed by the NHS in England for purposes that support NHS activities in England. Any person not employed by the NHS, or who is working for the NHS outside England, who wishes to download / copy NPC materials for purposes other than their personal use should seek permission first from the NPC.
Email: copyright@npc.nhs.uk Copyright 2006

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