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Smoking Cessation Strategies in Patients with Peripheral Arterial Disease: An Evidence-based Approach

  • Author Footnotes
    NO LABEL *Corresponding author. Simon D.Hobbs, Vascular Research Fellow, University Department of Vascular Surgery, Research Institute, Birmingham Heartlands and Solihull NHS Trust (Teaching), Lincoln House, Bordesley Green East, Birmingham B9 5SS, UK; Email: [email protected]
    S.D. Hobbs
    Footnotes
    NO LABEL *Corresponding author. Simon D.Hobbs, Vascular Research Fellow, University Department of Vascular Surgery, Research Institute, Birmingham Heartlands and Solihull NHS Trust (Teaching), Lincoln House, Bordesley Green East, Birmingham B9 5SS, UK; Email: [email protected]
    Affiliations
    University Department of Vascular Surgery, Research Institute, Birmingham Heartlands and Solihull NHS Trust (Teaching), Lincoln House, Bordesley Green East, Birmingham B9 5SS, UK
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  • A.W. Bradbury
    Affiliations
    University Department of Vascular Surgery, Research Institute, Birmingham Heartlands and Solihull NHS Trust (Teaching), Lincoln House, Bordesley Green East, Birmingham B9 5SS, UK
    Search for articles by this author
  • Author Footnotes
    NO LABEL *Corresponding author. Simon D.Hobbs, Vascular Research Fellow, University Department of Vascular Surgery, Research Institute, Birmingham Heartlands and Solihull NHS Trust (Teaching), Lincoln House, Bordesley Green East, Birmingham B9 5SS, UK; Email: [email protected]

      Abstract

      Introduction. Smoking is the single most important aetiological factor for the development and progression of atherosclerosis. Unfortunately, most patients receive little or no treatment for their nicotine addiction. This review aims to make evidence based recommendations for smoking cessation as part of a comprehensive delivery of best medical therapy to patients with peripheral arterial disease.
      Methods. A search of MEDLINE (1966 to 2003) and the Cochrane library was undertaken for studies relating to smoking cessation. Major priority was given to meta-analyses of randomised controlled trials including Cochrane reviews.
      Results. Physician advise, nicotine replacement therapy and Bupropion are all evidence based treatments that have success in increasing the likelihood of permanent smoking cessation. A basic understanding of the psychology of addictive behaviour is essential so that appropriate advice and treatment can be tailored to individual patients.
      Conclusions. Complete and permanent smoking cessation is by far the most clinically and cost effective intervention in patients with atherosclerosis. Greater awareness of smoking cessation strategies, by clinicians treating vascular patients, is essential for the effective delivery of best medical therapy.

      Keywords

      Introduction

      So-called ‘best medical therapy’ (BMT) is now widely accepted as the mainstay of treatment for patients with peripheral arterial disease (PAD).
      • Burns P
      • Gough S
      • Bradbury AW
      Management of peripheral arterial disease in primary care.
      • Burns PJ
      • Lima E
      • Bradbury AW
      What constitutes best medical therapy for peripheral arterial disease?.
      Smoking is the single most important aetiological factor for the development and progression of atherosclerosis (Table 1), with other factors such as hyperlipidaemia contributing a more minor role.
      • Kannel WB
      • Shurtleff D
      The Framingham study. Cigarettes and the development of intermittent claudication.
      • Cole CW
      • Hill GB
      • Farzad E
      • Bouchard A
      • Moher D
      • Rody K
      • et al.
      Cigarette smoking and peripheral arterial occlusive disease.
      For this reason, it has been argued that it is clinically and cost-ineffective to commence patients on anti-platelet and lipid-lowering agents if they continue to smoke; although the authors would not agree with this view, as it is not evidence-based. Unfortunately, most patients get little or no treatment for their nicotine addiction and smoking cessation rates remain depressingly low.
      • Burns PJ
      • Lima E
      • Bradbury AW
      Second best medical therapy.
      Table 1The association between smoking and PAD
      At least 80% of PAD patients are current or ex-smokers
      • Fowkes FGR
      • Housley E
      • Riemersma RA
      • Macintyre CCA
      • Cawood EHH
      • Prescott RJ
      • et al.
      Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischaemic heart disease in the Edinburgh artery study.
      • Hirsch AT
      • Treat-Jacobson D
      • Lando HA
      • Hatsukami DK
      The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the treatment of peripheral arterial disease.
      Smokers are 16 times more likely to develop PAD than non-smokers
      • Cole CW
      • Hill GB
      • Farzad E
      • Bouchard A
      • Moher D
      • Rody K
      • et al.
      Cigarette smoking and peripheral arterial occlusive disease.
      Smokers develop PAD 10 years earlier than non-smokers
      • Lassila R
      • Lepantalo M
      Cigarette smoking and the outcome after lower limb arterial surgery.
      Continued smoking is associated with:
      •disease progression
      • Jonason T
      • Bergstrom R
      Cessation of smoking in patients with intermittent claudication.
      • Gardner AW
      The effect of cigarette smoking on exercise capacity in patients with intermittent claudication.
      •increased bypass graft failure rates
      • Stonebridge PA
      • Bradbury AW
      • Murie JA
      Continued smoking and the results of vascular reconstruction.
      • Wiseman S
      • Powell J
      • Greenhalgh R
      • McCollum C
      • Kenchington G
      • Alexander C
      • et al.
      The influence of smoking and plasma factors on prosthetic graft patency.
      • Carty CS
      • Huribal M
      • Marsan BU
      • Ricotta JJ
      • Dryjski M
      Nicotine and its metabolite cotinine are mitogenic for human vascular smooth muscle cells.
      •a 5-year mortality of around 40–50%
      • Hirsch AT
      • Treat-Jacobson D
      • Lando HA
      • Hatsukami DK
      The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the treatment of peripheral arterial disease.
      •a 50% reduction in the chance of surviving for 5 years after bypass surgery
      • Faulkner KW
      • House AK
      • Castleden WM
      The effect of cessation of smoking on the accumulative survival rates of patients with symptomatic peripheral vascular disease.
      Smoking cessation is associated with a rapid reduction in cardiovascular risk and a slower but sustained reduction in the risk of both respiratory and non-respiratory cancers
      • Samet JM
      The health benefits of smoking cessation.
      In this article, we review the literature and make evidence-based recommendations regarding smoking cessations strategies as part of a comprehensive delivery of BMT to PAD patients.

      Methods

      A search of MEDLINE (1966–2003) and the Cochrane Library was performed to identify articles relating to smoking cessation. Search terms included ‘smoking cessation’, ‘nicotine replacement therapy’ (NRT), ‘Bupropion’ or ‘Zyban’, combined, where possible, with ‘peripheral vascular/arterial disease’. Cross-referencing from the reference lists of major relevant articles identified further papers. The medical literature is awash with evidence on smoking cessation and as such, highest priority was given to meta-analyses of randomised controlled trials including Cochrane reviews.

       Nicotine as a drug of addiction

      Nicotine ranks alongside heroin and cocaine as one of the most addictive known substances and cigarettes represent the most effective means of delivering of nicotine to the brain.
      • Tobacco Advisory Group, Royal College of Physicians
      Nicotine Addiction in Britain.
      Perhaps not surprising, therefore, that although 70% of smokers express a desire to stop, less than a third attempt to do so and only 2% succeed each year, most after several failed quit attempts.
      • Moxham J
      Nicotine addiction.

       The trans-theoretical model

      Before specifically discussing smoking cessation strategies it is necessary to understand something of the psychology of addictive behaviour modification. There are many different paradigms to chose from but the trans-theoretical model is probably the most widely used cognitive framework and describes progression through five stages (Fig. 1).
      • Prochaska JO
      • DiClemente CC
      • Norcross JC
      In search of how people change: applications to addictive behaviours.
      Pre-contemplation.
      Figure thumbnail gr1
      Fig. 1The transtheoretical model of intentional behavioural change as applied to smoking. Figures in brackets represent the proportion of smokers within the various stages.
      • Prochaska JO
      • DiClemente CC
      • Norcross JC
      In search of how people change: applications to addictive behaviours.
      The individual has no intention of changing their behaviour (in this case smoking) in the foreseeable future and is un-, or under-, aware that their behaviour (smoking) is the cause of their problem.
      Contemplation. The individual has become aware that smoking is the problem and has expressed an intention to stop within 6 months. This most frequently occurs following the diagnosis of a smoking related problem. In this stage patients weigh up the pros and cons of smoking cessation and, hopefully, conclude that they should make a quit attempt at some point in the future.
      Preparation. The individual intends to stop smoking in the near future (<1 month). People at this stage have frequently had previous unsuccessful quit attempts and often make (ineffective) behavioural modifications such as cutting down the numbers of cigarettes smoked.
      Action. The individual stops smoking and maintains early abstinence. Significant effort is required and it is at this point that control of withdrawal symptoms (Table 2) is so important to success.
      Maintenance. This is reached 6 months after successful abstinence and continued efforts are made to prevent relapse.
      Table 2Prevalence and duration of nicotine withdrawal symptoms.
      • West RJ
      Acute effects of stopping smoking.
      SymptomDurationPrevalence (%)
      Irritability/aggression<4 weeks50
      Depression<4 weeks60
      Restlessness<4 weeks60
      Poor concentration<2 weeks60
      Increased appetite>10 weeks70
      Increase in weight (6–8lbsavg.)Long-term>80
      Light-headedness<48 h10
      Night-time awakenings<1 week25

       Physician advice

      A Cochrane Collaboration review of pooled data from 16 trials found a small but significant benefit from brief physician advice compared to no advice (odds ratio [OR] 1.69) and suggested that more frequent advice might be marginally more effective.
      • Silagy C
      • Stead LF
      Physician advice for smoking cessation (Cochrane Review).
      It is essential therefore, that effective advice (the five As) is delivered at every possible opportunity (Table 3).
      • Anderson JE
      • Jorenby DE
      • Scott WJ
      • Fiore MC
      Treating tobacco use and dependence: an evidence-based clinical practice guideline for tobacco cessation.
      • Karnath B
      Smoking cessation.
      The primary benefit of cognitive paradigms, such as the trans-theoretical model, is as an aid to physicians in understanding that patients at different stages require different levels and types of support.
      • Cote M
      Vascular nurse as a smoking cessation specialist.
      For example, it is unrealistic to expect ‘pre-contemplators’ to stop smoking immediately. Instead, the aim should be to increase their awareness of the problem in the hope of down-staging them to the ‘contemplation’ stage. Contemplators require repeated reinforcement and encouragement to follow through with their intentions. It is particularly important to recognise when patients are in the ‘preparation’ stage as it is here that they are most responsive, and where adjunctive therapies, such as NRT or bupropion (Zyban), as well as referral to a specialist clinic, are most effective. There is no evidence that ‘cutting down’ the numbers of cigarettes smoked, or smoking brands with a lower tar or nicotine content, aids the quit attempt.
      • Moxham J
      Nicotine addiction.
      Patients who cut down often subconsciously smoke more efficiently to compensate for the increased fluctuations in blood nicotine levels and may, paradoxically, become more dependent on smoking. Rather, patients should be encouraged to set a specific date within the next couple of weeks on which they will stop completely. Some authorities actually recommend encouraging clients to ‘over-smoke’ prior to the quit attempt on the grounds that this will leave the client remembering the unpleasant effects of smoking such as agitation and nausea. Home, family, work and leisure circumstances need to be appropriately modified prior to the quit date. For example, the quit attempt is far more likely to be successful if other smoking members of the household stop at the same time, and packets of cigarettes and other smoking equipment (lighters, ashtrays) are discarded. Most patients require three or four such quit attempts before finally being successful (abstinence >6 months) and even beyond this point there are significant relapse rates.
      Table 3Suggested guidelines for physician advice for smoking cessation (the five As).
      • Anderson JE
      • Jorenby DE
      • Scott WJ
      • Fiore MC
      Treating tobacco use and dependence: an evidence-based clinical practice guideline for tobacco cessation.
      • Karnath B
      Smoking cessation.
      AskAt every patient contact episode enquire about current and past smoking status, previous ‘quit attempts’ and previous experience with NRT
      AdviseStrongly advise all smokers to quit. Educate all smokers about the risks of continued smoking and the benefits of cessation
      AssessIdentify the smoker's current stage in the transtheoretical model
      AssistAll patients in the preparation stage should be targeted for further intervention and offered NRT or bupropion
      ArrangeSuitable follow-up needs to be arranged and referral to a smoking cessation clinic needs to be considered

       Assessing cigarette intake

      One of the inherent problems with self-reported cigarette consumption is that it correlates poorly with blood nicotine levels because it does not take into account the type of cigarette, depth and frequency of inhalation, and the completeness with which each cigarette is smoked.
      • Idle JR
      Titrating exposure to tobacco smoke using cotinine—a minefield of misunderstanding.
      An accurate assessment of cigarette consumption is useful to motivate abstinence by providing feedback and to verify self-reports of abstinence.
      The most commonly used assessment tool in smoking cessation clinics is the measurement of exhaled breath carbon monoxide (CO). CO is measured in parts per million (ppm). Values of 0–6 ppm indicate a non-smoker, 7–10 ppm a light-smoker, 10–20 ppm a moderate smoker and >20 ppm a heavy smoker. Measurement of exhaled CO is quick and easy to perform in the clinical setting. However, it has the drawback that CO is not specific to cigarette smoke and, because CO has a short half life (3–5 h), the levels relate to the number of cigarettes smoked that particular day and levels fall to normal within 24 h of abstinence.
      A more sensitive and specific method of quantifying cigarette consumption is the measurement of cotinine.
      • Jarvis MJ
      • Tunstall-Pedoe H
      • Feyerabend C
      • Vesey C
      • Saloojee Y
      Comparison of tests used to distinguish smokers from non-smokers.
      Cotinine is the primary metabolite of nicotine and can be detected in serum, saliva and urine. Cotinine has a long half-life (16 h) and, therefore, fluctuates less than CO on a day-to-day basis and can detect smoking over the preceding 3–4 days. Unlike CO, as cotinine is measured in the laboratory the results cannot be fed back immediately to the patient in the clinic. Until near-patient cotinine assays become commercially available and affordable, its use will probably be limited as a research tool.

       Nicotine replacement therapy

      All patients in the preparation stage should be offered NRT (or Zyban, see below). NRT is used to reduce nicotine withdrawal symptoms as patients pass from the preparation into the action stage (Table 2). No current NRT formulation can match cigarette smoking in terms of the rate and concentration of nicotine delivery to the brain (10–20 s) (Fig. 2).
      Figure thumbnail gr2
      Fig. 2Illustration of the peak plasma nicotine levels obtained with a variety of nicotine delivery systems.
      • Russell MAH
      Nicotine intake and its regulation by smokers.
      Nevertheless, a Cochrane review of 110 trials has proved beyond reasonable doubt that NRT, in all its forms, is 1.7–2.3 times more effective than placebo at achieving maintained smoking cessation (Fig. 3).
      • Silagy C
      • Lancaster T
      • Stead L
      • Mant D
      • Fowler G
      Nicotine replacement therapy for smoking cessation (Cochrane Review).
      In the primary care setting, NRT can be expected to improve quit rates from 5 to 10% and, in more intensive settings, from 10 to 20%.
      • Raw M
      • McNeill A
      • West R
      Smoking cessation guidelines for health professionals.
      There are limited data on the effectiveness of NRT in specific subgroups, such as those with cardiovascular or peripheral vascular disease.
      • NICE
      A rapid and systematic review of the clinical and cost effectiveness of bupropion SR and nicotine replacement therapy (NRT) for smoking cessation.
      However, it is widely agreed that NRT is safe and does not lead to an excess of cardiovascular events.
      • McRobbie H
      • Hajek P
      Nicotine replacement therapy in patients with cardiovascular disease: guidelines for health professionals.
      • Joseph AM
      • Norman SM
      • Ferry LH
      • Prochazka AV
      • Westman EC
      • Steele BG
      • et al.
      The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease.
      • Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease
      Nicotine replacement therapy for patients with coronary artery disease.
      There is no level I evidence to support the superiority of any particular NRT formulation or dose.
      • NICE
      A rapid and systematic review of the clinical and cost effectiveness of bupropion SR and nicotine replacement therapy (NRT) for smoking cessation.
      Patches are probably easiest to use while the gum, nasal spray and inhaler offer more control over the dose and speed of delivery.
      Figure thumbnail gr3
      Fig. 3Odds ratios of successful smoking cessation with the various forms of nicotine replacement therapy.
      • Silagy C
      • Lancaster T
      • Stead L
      • Mant D
      • Fowler G
      Nicotine replacement therapy for smoking cessation (Cochrane Review).
      The patch is available in 16-hour and 24-hour preparations and in a variety of doses; however, there is no proven difference in efficacy between the two preparations.
      • Daughton DM
      • Heatley SA
      • Prendergast JJ
      • Causey D
      • Knowles M
      • Rolf CN
      • et al.
      Effect of transdermal nicotine delivery as an adjunct to low-intervention smoking cessation therapy. A randomized, placebo-controlled, double-blind study.
      Pragmatically, it is recommended to reserve the 24-hour patch for those with early morning cravings because it may lead to insomnia in less dependent smokers. The level of dependence should determine the dose of the patch.
      • NICE
      Guidance on the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation.
      It is applied first thing in the morning and the manufacturers recommend gradually reducing the strength of the patch over time. However, research has shown that stopping the patch abruptly is just as effective.
      • Silagy C
      • Lancaster T
      • Stead L
      • Mant D
      • Fowler G
      Nicotine replacement therapy for smoking cessation (Cochrane Review).
      • NICE
      A rapid and systematic review of the clinical and cost effectiveness of bupropion SR and nicotine replacement therapy (NRT) for smoking cessation.
      Nicotine gum is available in 2 and 4 mg doses, the latter is recommended for those who smoke more than 20 cigarettes per day. Initially, about 12–15 pieces are required per day aiming to reduce the amount over a period of 2–3 months. The gum needs to be chewed until the taste is strong and then parked between the cheek and the gum to allow slow absorption via the buccal mucosa. The tablets and lozenges work in a similar way to the gum. They are dissolved under the tongue and nicotine is absorbed via the buccal membrane. The taste of these preparations often reduces compliance, however, if it is stressed to the patients that they are medications and not confectionary the taste quickly becomes tolerated. The nicotine inhaler resembles a cigarette and is useful for those who miss the hand-to-mouth movements of smoking. It is important to appreciate that the nicotine from the inhaler is absorbed via the buccal membrane and not via the lungs. The nasal spray is the most effective and rapidly absorbed of the NRT products, it can, however, cause nasal and throat irritation that is not tolerated by one in three patients. Although currently unlicensed, pooled data from five trials suggest that combination therapy, for example using the patch continuously with the gum as required, increases quit rates.
      • Silagy C
      • Lancaster T
      • Stead L
      • Mant D
      • Fowler G
      Nicotine replacement therapy for smoking cessation (Cochrane Review).
      • NICE
      A rapid and systematic review of the clinical and cost effectiveness of bupropion SR and nicotine replacement therapy (NRT) for smoking cessation.
      Combination therapy should be reserved for those who are unsuccessful quitting with a single type of NRT. The contraindications and side effects of NRT are highlighted in Table 4.
      Table 4Contraindications and side effects of bupropion and nicotine replacement products
      ContraindicationsSide effects
      BupropionHistory of seizuresDry mouth
      Eating disorderInsomnia
      CNS tumourSeizures (1:1000)
      Acute alcohol or benzodiazepine withdrawal
      NRTTransdermal patchLocalised skin rash
      Insomnia (24 h patch)
      GumThroat irritation
      Indigestion
      Tablet/LozengeSevere cardiovascular diseaseAs for gum
      Recent myocardial infarctionAphthous ulceration
      Recent cerebrovascular event
      InhalerAs for gum
      Cough
      Dry mouth
      Nasal sprayAs for gum
      Nasal irritation
      Epistaxis

       Bupropion

      Nicotine stimulates dopaminergic pathways in the mesolimbic system, an area of the brain associated with dependence on other psychoactive drugs. Bupropion inhibits the re-uptake of both noradrenaline and dopamine and it is probably this activity in the mesolimbic system, rather than its anti-depressant effects, that accounts for its utility as an aid to smoking cessation.
      • Holm KJ
      • Spencer CM
      Bupropion: a review of its use in the management of smoking cessation.
      • Peters MJ
      • Morgan LC
      The pharmacotherapy of smoking cessation.
      A meta-analysis of 10 placebo-controlled, double-blind, randomised controlled trials involving almost 4000 patients has shown that bupropion results in significantly higher abstinence rates (OR 2.16).
      • NICE
      A rapid and systematic review of the clinical and cost effectiveness of bupropion SR and nicotine replacement therapy (NRT) for smoking cessation.
      One of two studies directly comparing NRT with bupropion showed the latter to be more effective, and a single study has shown a combination of bupropion and NRT to be more effective than bupropion alone.
      • Jorenby DE
      • Leischow SJ
      • Nides MA
      • Rennard SI
      • Johnston JA
      • Hughes AR
      • et al.
      A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.
      Smokers in the preparation stage should take 150 mg bupropion daily for 6 days and then increase to 150 mg twice daily. The quit attempt is delayed for a further 1–2 weeks to allow time for the drug to work maximally and the prescription continued for a further 6 weeks. Patients have to be well motivated and drug therapy should be combined with strong support and encouragement. Bupropion is associated with more side effects than NRT. Specifically seizures occur in 1 in 1000 patients and therefore bupropion is contraindicated in patients with any history of a seizure (Table 4).

       Specialist smoking clinics

      Specialist smoking clinics offer multi-session programmes that combine behavioural support with NRT/Bupropion. Specialist clinics report higher maintained cessation rates compared to brief interventions. It may be argued that this is a result of increased motivation among patients who attend such clinics, however, these patients also tend to be more highly dependent.
      • Hajek P
      • West R
      Treating nicotine dependence: the case for specialist smoker's clinics.
      Nonetheless, national guidelines recommended that all patients should be offered referral to a smoking cessation clinic
      • West R
      • McNeill A
      • Raw M
      Smoking cessation guidelines for health professionals: an update.
      although it is appreciated that the majority of smokers will not wish to receive specialist help.
      • Hajek P
      • West R
      Treating nicotine dependence: the case for specialist smoker's clinics.
      These clinics should be centrally based in health districts since it is unlikely that sufficient demand could be generated in single primary care practices to make local clinics cost-effective.
      • Hajek P
      • West R
      Treating nicotine dependence: the case for specialist smoker's clinics.

       Other interventions

      Evidence exists to show that acupuncture, acupressure, hypnotherapy, aversive smoking and antidepressants are ineffective.
      • White AR
      • Rampes H
      • Ernst E
      Acupuncture for smoking cessation (Cochrane Review).
      • Abbot NC
      • Stead LF
      • White AR
      • Barnes J
      Hypnotherpay for smoking cessation (Cochrane Review).
      • Hajek P
      • Stead LF
      Aversive smoking for smoking cessation (Cochrane review).
      • Hughes JR
      • Stead LF
      • Lancaster T
      Antidepressants for smoking cessation (Cochrane review).
      However, some of this evidence is based on small trials and further research in some areas, for example hypnotherapy, is probably warranted.

      Summary

      Complete and permanent cessation of smoking is by far the most clinically and cost-effective intervention in patients with atherosclerosis, including PAD: (NRT/Zyban <£2000 per Life Year Gained [LYG]; statins £13,000 per LYG
      • NICE
      Guidance on the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation.
      ). Yet, many health care professionals, even those dealing on a daily basis with ‘vascular’ patients are ignorant of the principles and practice of smoking cessation strategies and quit rates remain unacceptably low. This almost certainly reflects the time and resource consuming nature of cessation counselling.
      Each time a patient is assessed, their current smoking status and ‘stage’ needs to be actively identified and recorded. Patients within different stages require different levels of support, and advice must be tailored with this in mind. The initial aim is to provide repeated advice to ‘down stage’ patients into the preparation stage. Once there, patients can be targeted for more intensive treatments. NRT and bupropion are evidence-based therapies and need to be discussed in relation to a ‘quit date’ with every patient who has entered the preparation stage. Early relapse is common and smokers, just like other ‘drug addicts’, need continuing (life-long) support to deal with their craving and maintain abstinence.

      References

        • Burns P
        • Gough S
        • Bradbury AW
        Management of peripheral arterial disease in primary care.
        Br Med J. 2003; 326: 584-588
        • Burns PJ
        • Lima E
        • Bradbury AW
        What constitutes best medical therapy for peripheral arterial disease?.
        Eur J Vasc Endovasc Surg. 2002; 24: 6-12
        • Kannel WB
        • Shurtleff D
        The Framingham study. Cigarettes and the development of intermittent claudication.
        Geriatrics. 1973; 28: 61-68
        • Cole CW
        • Hill GB
        • Farzad E
        • Bouchard A
        • Moher D
        • Rody K
        • et al.
        Cigarette smoking and peripheral arterial occlusive disease.
        Surgery. 1993; 114: 753-757
        • Burns PJ
        • Lima E
        • Bradbury AW
        Second best medical therapy.
        Eur J Vasc Endovasc Surg. 2002; 24: 400-404
        • Tobacco Advisory Group, Royal College of Physicians
        Nicotine Addiction in Britain.
        Royal College of Physicians,, London2000
        • Moxham J
        Nicotine addiction.
        Br Med J. 2000; 320: 391-392
        • Prochaska JO
        • DiClemente CC
        • Norcross JC
        In search of how people change: applications to addictive behaviours.
        Am Psychol. 1992; 47: 1102-1114
        • Silagy C
        • Stead LF
        Physician advice for smoking cessation (Cochrane Review).
        The Cochrane Library, Update Software,, Oxford2002 (Issue 4)
        • Anderson JE
        • Jorenby DE
        • Scott WJ
        • Fiore MC
        Treating tobacco use and dependence: an evidence-based clinical practice guideline for tobacco cessation.
        Chest. 2002; 121: 932-941
        • Karnath B
        Smoking cessation.
        Am J Med. 2002; 112: 399-405
        • Cote M
        Vascular nurse as a smoking cessation specialist.
        J Vasc Nurs. 2000; 18: 47-53
        • Idle JR
        Titrating exposure to tobacco smoke using cotinine—a minefield of misunderstanding.
        J Clin Epidemiol. 1990; 43: 313-317
        • Jarvis MJ
        • Tunstall-Pedoe H
        • Feyerabend C
        • Vesey C
        • Saloojee Y
        Comparison of tests used to distinguish smokers from non-smokers.
        Am J Public Health. 1987; 77: 1435-1438
        • Silagy C
        • Lancaster T
        • Stead L
        • Mant D
        • Fowler G
        Nicotine replacement therapy for smoking cessation (Cochrane Review).
        The Cochrane Library, Update Software,, Oxford2002 (Issue 4)
        • Raw M
        • McNeill A
        • West R
        Smoking cessation guidelines for health professionals.
        Thorax. 1998; 53: S1-S19
        • NICE
        A rapid and systematic review of the clinical and cost effectiveness of bupropion SR and nicotine replacement therapy (NRT) for smoking cessation.
        Technology Appraisal Guidance. 2002; 39 (National Institute for Clinical Excellence) ([Accessed: 16-2-2003])
        • McRobbie H
        • Hajek P
        Nicotine replacement therapy in patients with cardiovascular disease: guidelines for health professionals.
        Addiction. 2001; 96: 1547-1551
        • Joseph AM
        • Norman SM
        • Ferry LH
        • Prochazka AV
        • Westman EC
        • Steele BG
        • et al.
        The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease.
        N Engl J Med. 1996; 335: 1792-1798
        • Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease
        Nicotine replacement therapy for patients with coronary artery disease.
        Arch Intern Med. 1994; 154: 989-995
        • Daughton DM
        • Heatley SA
        • Prendergast JJ
        • Causey D
        • Knowles M
        • Rolf CN
        • et al.
        Effect of transdermal nicotine delivery as an adjunct to low-intervention smoking cessation therapy. A randomized, placebo-controlled, double-blind study.
        Arch Intern Med. 1991; 151: 749-752
        • NICE
        Guidance on the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation.
        Technology Appraisal Guidance. 2002; 39 (National Institute for Clinical Excellence) ([Accessed, 16-2-2002])
        • Holm KJ
        • Spencer CM
        Bupropion: a review of its use in the management of smoking cessation.
        Drugs. 2000; 59: 1007-1024
        • Peters MJ
        • Morgan LC
        The pharmacotherapy of smoking cessation.
        Med J Aust. 2002; 176: 486-490
        • Jorenby DE
        • Leischow SJ
        • Nides MA
        • Rennard SI
        • Johnston JA
        • Hughes AR
        • et al.
        A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.
        N Engl J Med. 1999; 340: 685-691
        • Hajek P
        • West R
        Treating nicotine dependence: the case for specialist smoker's clinics.
        Addiction. 1998; 93: 637-640
        • West R
        • McNeill A
        • Raw M
        Smoking cessation guidelines for health professionals: an update.
        Thorax. 2000; 55: 987-999
        • White AR
        • Rampes H
        • Ernst E
        Acupuncture for smoking cessation (Cochrane Review).
        The Cochrane Library, Update Software,, Oxford2002 (Issue 4)
        • Abbot NC
        • Stead LF
        • White AR
        • Barnes J
        Hypnotherpay for smoking cessation (Cochrane Review).
        The Cochrane Library, Update Software,, Oxford2002 (Issue 4)
        • Hajek P
        • Stead LF
        Aversive smoking for smoking cessation (Cochrane review).
        The Cochrane Library, Update Software,, Oxford2002 (Issue 4)
        • Hughes JR
        • Stead LF
        • Lancaster T
        Antidepressants for smoking cessation (Cochrane review).
        The Cochrane Library, Update Software,, Oxford2002 (Issue 4)
        • Fowkes FGR
        • Housley E
        • Riemersma RA
        • Macintyre CCA
        • Cawood EHH
        • Prescott RJ
        • et al.
        Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischaemic heart disease in the Edinburgh artery study.
        Am J Epidemiol. 1992; 135: 331-340
        • Hirsch AT
        • Treat-Jacobson D
        • Lando HA
        • Hatsukami DK
        The role of tobacco cessation, antiplatelet and lipid-lowering therapies in the treatment of peripheral arterial disease.
        Vasc Med. 1997; 2: 243-251
        • Lassila R
        • Lepantalo M
        Cigarette smoking and the outcome after lower limb arterial surgery.
        Acta Chirurgica Scand. 1988; 154: 635-640
        • Jonason T
        • Bergstrom R
        Cessation of smoking in patients with intermittent claudication.
        Acta Med Scand. 1987; 221: 253-260
        • Gardner AW
        The effect of cigarette smoking on exercise capacity in patients with intermittent claudication.
        Vasc Med. 1996; 1: 181-186
        • Stonebridge PA
        • Bradbury AW
        • Murie JA
        Continued smoking and the results of vascular reconstruction.
        Br J Surg. 1994; 81: 51-52
        • Wiseman S
        • Powell J
        • Greenhalgh R
        • McCollum C
        • Kenchington G
        • Alexander C
        • et al.
        The influence of smoking and plasma factors on prosthetic graft patency.
        Eur J Vasc Surg. 1990; 4: 57-61
        • Carty CS
        • Huribal M
        • Marsan BU
        • Ricotta JJ
        • Dryjski M
        Nicotine and its metabolite cotinine are mitogenic for human vascular smooth muscle cells.
        J Vasc Surg. 1997; 25: 682-688
        • Faulkner KW
        • House AK
        • Castleden WM
        The effect of cessation of smoking on the accumulative survival rates of patients with symptomatic peripheral vascular disease.
        Med J Aust. 1983; 1: 217-219
        • Samet JM
        The health benefits of smoking cessation.
        Med Clin N Am. 1992; 76: 399-414
        • West RJ
        Acute effects of stopping smoking.
        http://www.rjwest.co.uk
        Date: 18-03-2003
        (Accessed)
        • Russell MAH
        Nicotine intake and its regulation by smokers.
        in: Tobacco Smoking and Nicotine: A Neurobiological Approach. Plenum Publishing Corporation,, New York1987: 25-50