in the name of god. smoking cessation as reduce cardiovascular disease risk factors by : dr. zahra...

IN THE NAME OF GOD

smoking cessation as reduce cardiovascular disease risk factors

By : Dr. Zahra Abna

Case scenario

A 27 year old heavy smoker man with positive history of cardiovascular

disease in his family refers to clinician , for reduce his cardiovascular risk

factors, which smoking cessation methods is more effective ?

P I C O

Patient or problem

smoking and positive family history for cardiovascular disease

Intervention

smoking cessation with :

• Silver acetate

• Cannabinoid type 1 receptor antagonists

• Anxiolytics

• Exercise interventions

• Aversive smoking

Comparison

• Drugs with plasebo

• exercise programme alone or exercise programme as an adjunct to

a cessation programme with a cessation programme alone

• aversion treatments with ’inactive’ procedures

Outcomes

smoking cessation for reduce risk factor of cardiovascular disease

Key words

• smoking cessation

• Silver acetate

• Cannabinoid type 1 receptor antagonists

• Anxiolytics

• Exercise interventions

• Aversive smoking

Silver acetate for smoking cessation

Tim Lancaster, Lindsay F Stead

1Department of Primary Care Health Sciences, University of Oxford, Oxford, UK

Editorial group: Cochrane Tobacco Addiction Group.

Publication status and date: New search for studies and content updated (no

change to conclusions), published in Issue 9, 2012.

Review content assessed as up-to-date: 14 August 2012.

Citation: Lancaster T, Stead LF. Silver acetate for smoking cessation. Cochrane

Database of Systematic Reviews 2012, Issue 9. Art. No.:

CD000191. DOI: 10.1002/14651858.CD000191.pub2.

Copyright © 2012 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd.

Background

Silver acetate produces an unpleasant taste when combined with

cigarettes, thereby producing an aversive stimulus.

It has beenmarketed in various forms with the aim of extinguishing

the urge to smoke, by pairing the urge with an unpleasant stimulus.

Objectives

The aim of this review was to determine the effectiveness of silver

acetate products (gum, lozenge, spray) in promoting smoking

cessation.

Search methods

We searched the Cochrane Tobacco Addiction Group specialised

trials register. Most recent search was in July 2012.

Selection criteria

We included randomised trials of silver acetate for smoking

cessation with reports of smoking status at least six months after

the beginning of treatment.

Data collection and analysis

We extracted data in duplicate on the type of subjects, the dose and

form of silver acetate, the outcome measures, method of

randomisation, and completeness of follow-up.

The main outcome measure was biochemically validated abstinence

from smoking after at least six months follow-up in patients

smoking at baseline. Subjects lost to follow-up were counted as

continuing smokers. Where appropriate, we performed meta-analysis

using a fixed effects model.

Main results

Two studies provided long-term follow-up data on patients

randomised to silver acetate or placebo. In one of these studies,

there was a third arm, randomised to 2mg nicotine gum.

The pooled risk ratio for quitting for silver acetate vs placebo was

1.04 (95% confidence interval 0.69 to 1.57).

Authors’ conclusions

Existing trials show little evidence for a specific effect of silver

acetate in promoting smoking cessation. The confidence intervals

for the ratio are quite wide. However, the upper limit of the

confidence intervals for a positive effect equates to an absolute

increase in the smoking cessation rate of about 4%. Any effect of

this agent is therefore likely to be smaller than nicotine

replacement therapy.

The lack of effect of silver acetate may reflect poor compliance with

a treatment whose rationale is to create an unpleasant stimulus.

P L A I N L A N G U A G E S U M M A R Y

Does silver acetate help people stop smoking

Silver acetate products (gum, lozenge, and spray) produce an unpleasant

metallic taste when combined with cigarettes, so they are used

as a form of aversion therapy for smoking. However, the review of trials

found little evidence to show that silver acetate helps smokers

quit. Any beneficial effect of silver acetate is likely to be very small, and

less than the effect already proven for nicotine replacement therapy.

B A C K G R O U N D

Silver acetate preparations produce an unpleasant, metallic taste

when combined with cigarettes. Their use for smoking cessation is

based on the principles of aversive conditioning, and is analogous

to the use of disulfiram (Antabuse) for alcoholism. That is, an

aversive stimulus (in this case taste) is systematically paired with a

behaviour (smoking) that the subject wishes to stop. Various silver

acetate products are available including lozenges, gum and sprays.

The aim of treatment is to encourage smokers to use silver acetate,

so that the act of smoking becomes unpleasant, and the urge

to smoke therefore diminished, or ideally, extinguished. Excessive

ingestion of silver can lead to the rare condition of argyrism. To

avoid this, a total dose of silver no greater than 756mg is recommended

and this limits the duration of silver acetate treatment.

M E T H O D S

• Criteria for considering studies for this review

Types of studies

Randomised controlled trials which report smoking status at least

sixmonths after intervention. Studies reporting follow-up between

3 and 6 months only were reviewed, but data were not included

in pooled analyses.

Types of participants

Adult patients who smoke.

Types of interventions

All randomised controlled comparisons of silver acetate with

placebo, or with other smoking cessation treatments were included.

Silver acetate products included lozenges, gums and sprays.

Types of outcome measures

The main outcome measure was sustained abstinence from smoking

at 6 to12 months. Only participants who met criteria for biochemically

validated cessation were counted as quitters.

Search methods for identification of studies

We searched theTobaccoAddictionReviewGroup specialised register

for trials, using the term ’silver acetate’ in the title or abstract,

or as a keyword. This register has been developed from regular

electronic searches of MEDLINE, EMBASE and PsycINFO, together

with handsearching of specialist journals, conference proceedings

and reference lists of previous trials and overviews.

The most recent search for trials was in July 2102 when the Register

included the results of searches of the Cochrane Central Register

of Controlled trials (CENTRAL), issue 7, 2012; MEDLINE

(via OVID) to update 20120622; EMBASE (via OVID) to week

201227; and PsycINFO (via OVID) to update 20120625. See

the Tobacco Addiction Group Module in the Cochrane Library

for full search strategies and list of other resources searched. We

also searched Clinicaltrials.gov using the terms ’silver acetate’ and

’smoking’.


All potentially eligible studies were reviewed by two authors (TL

and LS).Data were abstracted onto a data formwhich detailed the

methods of recruitment and randomisation, types of participants,

interventions and outcomes. A record was made of whether

abstinence was confirmed biochemically.

Trial results were expressed as risk ratios (number of quitters in

intervention group/total randomised to intervention)/(number of

quitters in control group/total randomised to control). Pooled

effects were estimated using aMantel-Haenszel fixed-effect model

(Deeks 2011).

R E S U L T S

Description of studies

Two randomised trialswith follow-up greater than sixmonthswere

identified. In the first (Jensen 1990) 6mg silver acetate chewing

gumwas compared to 2mg nicotine gum, and to ordinary chewing

gum in a three armed, randomised, open study. In the second

(Hymowitz 1996), 2.5mg silver acetate lozenges were compared

to placebo lozenges in a randomised double-blind study.

A third study (Malcolm 1986) was reviewed. In this study,

participants were randomised to silver acetate chewing gum or

placebo. This study was excluded from formal analysis because the

maximum follow-up was only four months.

Risk of bias in included studies

The studies were judged on their attempts to control bias in allocation,

assessment and analysis. All three were randomised, though

the precise method of randomisation was not stated in any of the

studies. One (Jensen 1990) was not blinded. Each of three studies

reviewed confirmed abstinence with biochemical verification. In

all studies, smokers lost to follow-up were counted as continuing

smokers in the analysis.

Effects of interventions

Two studies provided long-term follow-up of patients randomised

to silver acetate or placebo. In the first (Jensen 1990), there were

no significant differences in smoking status between patients randomised

to silver acetate chewing gum, nicotine gum or ordinary

chewing gum. In the second (Hymowitz 1996), 11/ 239 subjects

randomised to silver acetate lozenges had quit at one year, compared to 9/241

randomised to placebo. The combined estimate

for the risk ratio for quitting was 1.04 (95% confidence interval

0.69 to 1.57).

In the comparison between silver acetate and nicotine gum in

Jensen 1990 the risk ratio was 0.98 95% (CI 0.69 to 1.39).

In one further study (Malcolm 1986) 9/127 randomised to silver

acetate gumquit, compared to 4/142 randomised to placebo. This

study was not included in meta-analysis because follow-up was

only four months.

In all trials, the total dose of silver acetate was restricted to reduce

the chance of developing the rare outcome of argyrism (silver

deposition in body tissues), and no subject suffered this side-effect.

The main adverse effects reported were those expected from this

aversive stimulus; unpleasant tastes and sensations in the mouth,

and gastrointestinal disturbances.

D I S C U S S I O N

There is little evidence for a specific effect of silver acetate in

promoting smoking cessation.The confidence intervals for the

pooled risk ratio are quite wide, because the total number of

subjects studied with long-term follow-up is relatively small. The

upper limit of the confidence intervals for a positive effect equates

to an absolute increase in smoking cessation rate of about 4%. Such

an effect would, of course, be worth having.

However, given that other smoking cessation interventions produce

effects comparable to or larger than this (Stead 2008; Cahill 2012),

proving or disproving a small effect of silver acetate is unlikely to

have much clinical relevance. In a direct comparison between silver

acetate and nicotine gum, no advantages were seen for either

product over the other, but the numbers studied were small (Jensen

1990).

In part, the results may reflect the difficulties of complying with a

treatment whose rationale is to create an unpleasant stimulus.

A recent laboratory based study (Rose 2010) assessed the effect of

silver acetate on the taste of nicotine-containing or denicotinized

cigarettes, and nicotine inhaler.

Silver acetate mouth wash made the taste of both types of cigarette

less pleasant but did not affect the taste of the inhaler, implying

that silver acetate interacts with components other than nicotine.

The authors suggest that silver acetate could potentially be used in

combination with NRT products to reduce the chance that a recent

quitter who slipped and tried a cigarette would relapse completely.

A U T H O R S ’ C O N C L U S I O N S

Although a possible small effect of silver acetate in promoting

smoking cessation has not been disproved, any such effect is likely

to be very small, and less than that proven for nicotine replacement

therapy.There is therefore little role for silver acetate for promoting

smoking cessation in the clinical setting.

Cannabinoid type 1 receptor antagonists for smoking cessation

Kate Cahill, Michael H Ussher

Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. Division of

Population Health Sciences and Education, St George’s, University of London, London, UK


Publication status and date: Edited (no change to conclusions), published in Issue 7,

2012.

Review content assessed as up-to-date: 25 January 2011.

Citation: Cahill K, Ussher MH. Cannabinoid type 1 receptor antagonists for smoking

cessation. Cochrane Database of Systematic

Reviews 2011, Issue 3. Art. No.: CD005353. DOI: 10.1002/14651858.CD005353.pub4.


Background

Selective type 1 cannabinoid (CB1) receptor antagonists may assist

with smoking cessation by restoring the balance of the

endocannabinoid system, which can be disrupted by prolonged use

of nicotine. They also seek to address many smokers’ reluctance to

persist with a quit attempt because of concerns about weight gain.

Objectives

To determine whether selective CB1 receptor antagonists (currently

rimonabant and taranabant) increase the numbers of people

stopping smoking To assess their effects on weight change in

successful quitters and in those who try to quit but fail.

Search methods

We searched the Cochrane Tobacco Addiction Review Group

specialized register for trials, using the terms (’rimonabant’ or

’taranabant’) and ’smoking’ in the title or abstract, or as keywords.

We also searchedMEDLINE, EMBASE, CINAHL and PsycINFO, using

major MESH terms.

We acquired electronic or paper copies of posters of preliminary trial

results presented at the American Thoracic Society

Meeting in 2005, and at the Society for Research on Nicotine and

Tobacco EuropeanMeeting 2006. We also attempted to contact the

authors of ongoing studies of rimonabant, and Sanofi Aventis

(manufacturers of rimonabant). The most recent search was in

January 2011.

Selection criteria

Types of studies

Randomized controlled trials

Types of participants

Adult smokers

Types of interventions

Selective CB1 receptor antagonists, such as rimonabant and taranabant.

Types of outcome measures

The primary outcome is smoking status at a minimum of six months after the

start of treatment.We preferred sustained cessation rates

to point prevalence, and biochemically verified cessation to self-reported

quitting. We regarded smokers who drop out or are lost to

follow up as continuing smokers. We have noted any adverse effects of

treatment.

A secondary outcome is weight change associated with the cessation

attempt.

Main results

We found three trials which met our inclusion criteria, covering

1567 smokers (cessation: STRATUS-EU and STRATUS-US), and 1661

quitters (relapse prevention: STRATUS-WW).

At one year, the pooled risk ratio (RR) for quitting with rimonabant

20 mg was 1.50 (95% confidence interval (CI) 1.10 to 2.05).

No significant benefit was demonstrated for rimonabant at 5 mg

dosage. Adverse events included nausea and upper respiratory tract

infections.

In the relapse prevention trial, smokers who had quit on the 20 mg

regimen were more likely to remain abstinent on either active

regimen than on placebo; the RR for the 20 mg maintenance group

was 1.29 (95% CI 1.06 to 1.57), and for the 5 mg maintenance

group 1.30 (95% CI 1.06 to 1.59). There appeared to be no

significant benefit of maintenance treatment for the 5 mg quitters.

One trial of taranabant was not included in our meta-analyses, as it

followed participants only until end of treatment; at eight weeks it

found no benefit for treatment over placebo, with an OR of 1.2

(90% CI 0.6 to 2.5).

For rimonabant, weight gain was reported to be significantly lower

among the 20 mg quitters than in the 5 mg or placebo quitters.

During treatment, overweight or obese smokers tended to lose

weight, while normal weight smokers did not. For taranabant, weight

gain was significantly lower for 2-8 mg versus placebo at the end of

eight weeks of treatment.


From the trial reports available, rimonabant 20 mg may increase the

chances of quitting approximately 1½-fold. The evidence for

rimonabant in maintaining abstinence is inconclusive.

Rimonabant 20 mg may moderate weight gain in the long term.

Taranabant 2-8 mg may moderate weight gain, at least in the short term.

In 2008, development of both rimonabant and taranabant was discontinued

by the manufacturers.


Can cannabinoid type 1 receptor antagonists help smokers to quit,

and could they also reduce the amount of weight gained

during the quitting process?

Long-term use of nicotine can upset the endocannabinoid system in

the brain, which controls food intake and energy balance.

Rimonabant and similar drugs may help smokers to quit by

rebalancing the system, which then reduces nicotine and food

cravings.

We searched our own specialised register of controlled trials. We

also contacted Sanofi Aventis, the manufacturers of rimonabant,

and researchers who presented early findings at conferences.

We found two randomized controlled trials (RCTs) of rimonabant for

smoking cessation, covering 1567 smokers, and one RCT of

rimonabant for relapse prevention covering 1661 quitters.

The available information shows that rimonabant at the 20 mg dose

increased by 1½-fold the chances of not smoking at one year,

compared with placebo.

Rimonabant 5 mg did no better than placebo at any time point.

Anxiolytics for smoking cessation

Hughes JR, Stead LF, Lancaster T

Dept of Psychiatry, University of Vermont, Burlington, Vermont, USA. Department of

Primary Care Health Sciences, University of

Oxford, Oxford, UK. 3Department of Primary Health Care, University of Oxford, Oxford



2011.

Review content assessed as up-to-date: 4 October 2009.

Citation: Hughes JR, Stead LF, Lancaster T. Anxiolytics for smoking cessation. Cochrane

Database of Systematic Reviews 2000, Issue 4.

Art. No.: CD002849. DOI: 10.1002/14651858.CD002849.


Background

There are two reasons to believe anxiolytics might help in smoking

cessation. Anxiety may be a symptom of nicotine withdrawal.

Secondly, smoking could be due to an attempt to self-medicate an

anxiety problem.

Objectives

The aim of this review is to assess the effectiveness of anxiolytic

pharmacotherapy in aiding long term smoking cessation. The drugs

include buspirone; diazepam; doxepin; meprobamate;

ondansetron; and the beta-blockers metoprolol, oxprenolol and

propanolol.

Search methods


register (most recent search October 2009), which includes trials

indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and

conference abstracts.

Selection criteria

We considered randomized trials comparing anxiolytic drugs to

placebo or an alternative therapeutic control for smoking cessation.

We excluded trials with less than six months follow up.


We extracted data in duplicate on the type of study population, the

nature of the drug therapy, the outcome measures, method of

randomization, and completeness of follow up.

The main outcome measure was abstinence from smoking after at

least six months follow up in patients smoking at baseline. We used

themost rigorous definition of abstinence for each trial, and

biochemically validated rates if available. Where appropriate, we

performed meta-analysis of relative risks using a fixed effect model.

Main results

There was one trial each of the anxiolytics diazepam, meprobamate,

metoprolol and oxprenolol. There were two trials of the anxiolytic

buspirone. None of the trials showed strong evidence of an effect

for any of these drugs in helping smokers to quit. However,

confidence intervals were wide, and an effect of anxiolytics cannot

be ruled out on current evidence.


There is no consistent evidence that anxiolytics aid smoking

cessation, but the available evidence does not rule out a possible

effect.


Do pharmacotherapies which reduce anxiety help smokers to quit

Anxiety can contribute to increased smoking, and may be a smoking

withdrawal symptom. Medications to reduce anxiety (anxiolytics) may

theoretically help smokers trying to quit. There have not been many

trials, and none of them showed strong evidence of an effect on

quitting.

Aversive smoking for smoking cessation

Peter Hajek, Lindsay F Stead

Wolfson Institute of Preventive Medicine, Queen Mary’s School of Medicine and

Dentistry, London, UK. Department of Primary Care Health Sciences, University of

Oxford, Oxford, UK



2011.

Review content assessed as up-to-date: 14 October 2009.

Citation: Hajek P, Stead LF. Aversive smoking for smoking cessation. Cochrane

Database of Systematic Reviews 2001, Issue 3. Art. No.:

CD000546. DOI: 10.1002/14651858.CD000546.pub2.


Background

Aversion therapy pairs the pleasurable stimulus of smoking a

cigarette with some unpleasant stimulus. The objective is to

extinguish the urge to smoke.

Objectives

This review has two aims: First, to determine the efficacy of rapid

smoking and other aversive methods in helping smokers to stop

smoking; Second, to determine whether there is a dose-response

effect on smoking cessation at different levels of aversive

stimulation.

Search methods


register (latest search date October 2009) for studies which

evaluated any technique of aversive smoking.

Selection criteria

Randomized trials which compared aversion treatments with

’inactive’ procedures or which compared aversion treatments of

different intensity for smoking cessation. Trials must have reported

follow up of least six months from beginning of treatment.


We extracted data in duplicate on the study population, the type of

aversion treatment, the outcome measure,method of

randomization and completeness of follow up.

The outcome measure was abstinence from smoking at maximum

follow up, using the strictest measure reported by the authors.

Subjects lost to follow up were regarded as smokers. Where

appropriate, we performed meta-analysis using a fixed effect

model.

Main results

Twenty-five trials met the inclusion criteria. Twelve included rapid

smoking and nine used other aversion methods. Ten trials included

two or more conditions allowing assessment of a dose-response to

aversive stimulation. The odds ratio (OR) for abstinence following

rapid smoking compared to control was 2.01 (95% confidence

intervals (CI): 1.36 to 2.95). Several factors suggest that this finding

should be interpreted cautiously.

A funnel plot of included studies was asymmetric, due to the

relative absence of small stu negative results. Most trials had a

number of serious methodological problems likely to lead to

spurious positive results. The only trial using biochemical validation

of all self reported cessation gave a non-significant result.

Other aversion methods were not shown to be effective (OR 1.15,

95% CI 0.73 to 1.82). There was a borderline dose-response to the

level of aversive stimulation (OR 1.67, 95% CI 0.99 to 2.81).


The existing studies provide insufficient evidence to determine the

efficacy of rapid smoking, or whether there is a dose-response to

aversive stimulation. Milder versions of aversive smoking seem to

lack specific efficacy. Rapid smoking is an unproven method with

sufficient indications of promise to warrant evaluation using

modern rigorous methodology.


Does smoking in a way that is unpleasant help smokers to quit

Aversion treatments pair undesirable behaviours with negative

sensations. In smoking cessation, several approaches have been

suggested such as rapid smoking, which requires smokers to take a

puff every few seconds to make smoking unpleasant.

The results of the existing trials suggest that this may be effective,

but the evidence is not conclusive because most of the studies of

this approach have methodological problems.

A recent laboratory study also suggests that the method has an

active ingredient. Further research may be

worthwhile.

Exercise interventions for smoking cessation

Michael H Ussher, Adrian Taylor, Guy Faulkner

Division of Population Health Sciences and Education, St George’s, University of

London, London, UK. 2School of Sports & Health Sciences, University of Exeter, Exeter,

UK. 3Faculty of Physical Education and Health, University of Toronto, Toronto, Canada


Publication status and date: New search for studies and content updated (no change

to conclusions), published in Issue 1, 2012.

Review content assessed as up-to-date: 26 September 2011.

Citation: Ussher MH, Taylor A, Faulkner G. Exercise interventions for smoking

cessation. Cochrane Database of Systematic Reviews

2012, Issue 1. Art. No.: CD002295. DOI: 10.1002/14651858.CD002295.pub4.


Background

Taking regular exercise may help people give up smoking by

moderating nicotine withdrawal and cravings, and by helping to

manage weight gain.

Objectives

To determine whether exercise-based interventions alone, or

combined with a smoking cessation programme, are more effective

than a smoking cessation intervention alone.

Search methods

In July 2011, we searched the Cochrane Tobacco Addiction Group

Specialized Register for studies including the terms ’exercise’ or

’physical activity’. We also searchedMEDLINE, EMBASE, PsycINFO,

Dissertation Abstracts and CINAHL using the terms ‘exercise’

or ‘physical activity’ and ‘smoking cessation’.

Selection criteria

We included randomized trials which compared an exercise

programme alone, or an exercise programme as an adjunct to a

cessation programme, with a cessation programme, recruiting

smokers or recent quitters, and with a follow up of six months or

more.


We extracted data on study characteristics and smoking outcomes.

Because of differences in studieswe summarized the results

narratively, making no attempt at meta-analysis.

Main results

We identified 15 trials, seven of which had fewer than 25 people in

each treatment arm. They varied in the timing and intensity of

the smoking cessation and exercise programmes. Three studies

showed significantly higher abstinence rates in a physically active

group versus a control group at end of treatment.

One of these studies also showed a significant benefit for exercise

versus control on abstinence at the three-month follow up and a

benefit for exercise of borderline significance (p = 0.05) at the 12-

month follow up.

One study showed significantly higher abstinence rates for the

exercise group versus a control group at the three-month follow up

but not at the end of treatment or 12-month follow up. The other

studies showed no significant effect for exercise on abstinence.


Only one of the 15 trials offered evidence for exercise aiding

smoking cessation at a 12-month follow up. All the other trials were

too small to reliably exclude an effect of intervention, or included

an exercise intervention which was insufficiently intense to achieve

the desired level of exercise. Trials are needed with larger sample

sizes, sufficiently intense interventions, equal contact control

conditions, and measures of exercise adherence and change in

physical activity in both exercise and comparison groups.


Do exercise interventions help people quit smoking

Exercise is routinely recommended as an aid to smoking cessation by

specialist clinics and self-help materials. Fifteen trials have

compared an exercise programme plus a smoking cessation

programme, or an exercise programme alone, to a cessation

programme alone or a cessation programme plus a health education

programme, among smokers who were motivated to quit.

Since these studies used different types of exercise programmes, and

varied in the duration of follow up, the results were not combined.

In one study with a difference in quit rates of borderline significance,

the exercise component more than doubled the likelihood of not

smoking after 12 months.

in the name of god. smoking cessation as reduce cardiovascular disease risk factors by : dr. zahra...

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