Efficacy of Electronic Cigarettes in Smoking Cessation for Adult SmokersSusan Alaei, M.D. Candidate; Brittany Bartolome, M.D. Candidate; Colin Freedman, M.D. Candidate1

1University of Nevada School of Medicine, Reno

IntroductionWhile the complete cessation of smoking is the best form of treatment for smokers, the presence of nicotine in tobacco smoke makes overcoming the addictive properties of nicotine very difficult for those looking to quit smoking. Electronic cigarettes (“e-cigarettes”, EC) are a battery powered delivery system of nicotine that does not require combustion or smoke. Since being marketed in 2006, there has been a steady growth in EC sales, as they are advertised as containing fewer carcinogens compared to traditional cigarettes. Smokers have reported using ECs as a means of reducing smoking, thus contributing to its public attention as a safer smoking alternative or as an aid to help people in their efforts to quit. However, healthcare providers remain hesitant to encourage smokers to switch to ECs, as the efficacy and health risks of such a claim remain uncertain due to the lack sufficient evidence. This has ultimately prompted research on the short and long-term health consequences of frequent electronic cigarette use and whether ECs have, in fact, been effective at achieving smoking abstinence or reducing cigarette consumption, and if it exacerbates nicotine addiction. This information will undoubtedly prove useful as it will determine whether such devices can reduce the harms associated with smoking and be considered as an alternative therapy offered by physicians to smokers looking to quit smoking or inquiring about ECs.

QuestionAre electronic cigarettes more effective at helping adults smokers quit smoking compared to alternative smoking cessation aids?

P = Adult cigarette smokers (>18 years old)I = Electronic cigarettes (ECs)C = Alternative smoking cessation aids, including no interventionO = Smoking cessation

MethodologyA systematic review of articles was conducted using the PubMed database. Terms used for search included “electronic cigarette,” “e-cigarette,” “safety,” “smoking cessation,” and “tobacco use reduction.” Convenience was also considered in our literature search, as only papers that were free of cost or available through the Savitt Medical Library were accessed for the purposes of this review.

Criteria for considering studies for this reviewLiterature search was limited to human studies of adult (>18 years old) patient studies published within the last 5 years (2010 through 2015). We selected and evaluated articles based on subject design, which included selecting first for randomized control trials, where smokers were randomized to electronic cigarettes (ECs) or to a control condition and the measure of abstinence rates or changes in cigarette consumption were taken at a minimum of six months or longer to determine efficacy of ECs in aiding smoking cessation and reduction. Our search results offered few RCTs and thus our search was expanded to prospective and longitudinal based studies that exceeded at least a six month follow up period. We accepted studies regardless of their publication status.

Types of Outcomes MeasuredPrimary outcomes included cessation at the longest follow up point (at least six months) from start of intervention, measured using the strictest definition of abstinence, validated by biochemical results (carbon monoxide, thiocyanate, and other markers of tobacco use). Secondary outcomes included reduction in cigarette use at longest follow up point (at least six months) from start of intervention.

DiscussionOur review of studies found that ECs containing nicotine can aid in smoking cessation, while those without nicotine were not as effective. Regardless of nicotine enrichment, ECs have been effective in reducing tobacco cigarette consumption. It was found that compared to the nicotine transdermal patch, EC cessation rates were similar. However, in absence of cessation, ECs were far more effective in reducing the number of cigarettes used compared with the patch. Furthermore, the correlation between EC use and the reduction in the number of tobacco cigarettes suggests that the device does not contribute to increased nicotine addiction as previously questioned. Only one study found no correlation between EC use and either abstinence or reduction in cigarette consumption. However, this study did not have a clear definition of abstinence and the statistical power was lowered due to low reporting of EC use among participants.

ConclusionIn the population of people who have a long history of smoking, we would recommend EC use as an alternative to other smoking cessation aids that they may not feel are as helpful. We conclude that ECs are more effective in reducing cigarette consumption compared to the transdermal patch and ECs containing nicotine were more effective than those without. In terms of complete abstinence, ECs have similar efficacies as the transdermal patch. As a device that provides an additional means of smoking cessation in the effort to curb tobacco usage and subsequent tobacco harm, there are profound implications for the benefits of ECs in terms of public health. We would like to note, however,  that our review is limited to the short-term efficacy of EC and not its safety. We can therefore make no conclusions on the health consequences of EC use compared to alternative cessation methods.

Further ResearchOur review of these studies has been limited to understanding the short-term effects of continued EC use, thus prompting us to inquire and research further the longer-term use and possible health consequences. These studies have also been limited to the adult smoking population, but does not assess the risk of access to ECs and potential abuse among the adolescent population. While ECs have shown a potential for improving the population health, given its high acceptability in today’s society, we must first address whether accessibility in and of itself can result in future health problems not commonly associated with tobacco use.

References1 Bullen et al. (2013) “Electronic Cigarettes for smoking cessation: a randomised controlled trial.” Lancet 382:1629-372 Caponnetto et al. (2013) “Efficiency and Safety of an Electronic Cigarette (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study.” PLoS One 8(6):e66317.3 Grana et al. (2014) “A longitudinal analysis of electronic cigarette use and smoking cessation.” JAMA Int Med 174(5):812-3.4 Polosa et al. (2014) “Effectiveness and tolerability of electronic cigarette in real life: a 24-month prospective observational study.” Internal and Emergency Medicine 9(5):537-46.

AcknowledgementsDr. Julie Smith-Gagen and Dr. Mary Schultz for their guidance in our web search and ensuring our preparation for this review.

ResultsAUTHOR METHODS FINDINGS LIMITATIONS

Bullen  et  al,  (2013)1

•  657  par(cipants  (New  Zealand)  selected  via  exclusion  and  inclusion  criteria  from  newspaper  adver(sement  

•  4:4:1  ra(o  of  randomly  assigned  groups:  

•  Group  A:  nico(ne  ECs  •  Group  B:  nico(ne  patches  •  Group  C:  placebo  EC  (no  nico(ne)  •   Assessed  at  1,  3,  and  6  months  

for  abs(nence  (measured  eCO)  and  reported  smoked  cigareJes/day

•  Verified  abs(nence  of  7%  with  nico(ne  ECs  vs  5%  with  nico(ne  patches  vs  4%  with  placebo  ECs  

•  Insufficient  sta(s(cal  power  to  conclude  EC  superiority  to  patches  or  placebo  

•  ECs  were  modestly  effec(ve  at  helping  smokers  quit,  with  similar  achievement  of  abs(nence  as  nico(ne  patches

•  Effect  size  and  es(mates  of  abs(nence  were  markedly  op(mis(c,  thus  reducing  sta(s(cal  power  to  detect  differences    

•  Group  B  had  higher  loss  to  follow  up  and  withdrawal  rates    

•  Study  was  not  conducted  on  second  genera(on  ECs  

•  22%  loss  to  follow  up  rate  reduces  sta(s(cal  power  of  study  

•  Sampling  bias  as  convenience  sampling  was  used  in  the  selec(on  of  par(cipants

Randomized  Control  Trial

CaponneDo  et  al,  (2013)2

•  300  smokers  with  no  inten(on  to  quit  (Italy);  selected  via  exclusion  and  inclusion  criteria  from  EC  therapy  study  adver(sement    

•  1:1:1  ra(o  of  EC  containing  cartridges  given  to  3  groups:  

•  Group  A:  7.2mg  nico(ne  for  12  weeks    

•  Group  B:  6-­‐week  7.2  mg  nico(ne  followed  by  6-­‐week  5.4mg  nico(ne  

•  Group  C:  no  nico(ne  for  12  weeks    •  9  conducted  visits  to  measure  

cigareJe/day  use  and  eCO  levels

•  Median  number  of  cigareJes  per  day  and  exhaled  carbon  monoxide  levels  decreased  from  baseline  in  all  3  study  groups  at  each  visit    

•  Overall  number  of  cigareJes  per  day  decreased  from  21  to  13.9  (p<0.0001)  at  end  of  52-­‐week  study    

•  Complete  abs(nence  from  tobacco  smoked  was  documented  10.7%  and  8.7%  at  weeks  12  and  52  respec(vely  

•  Repor(ng  bias  as  it  was  unclear  if  the  original  inten(on  was  to  combine  the  two  nico(ne-­‐containing  EC  groups  or  not  

•  25%,  29.7%,  and  39%  drop  out  rate  at  follow  up  weeks  12,  24,  and  52,  respec(vely  contributes  to  a  reduced  sta(s(cal  power  of  the  study  

•  Sampling  bias  as  convenience  sampling  was  used  for  selec(on  of  par(cipants

Randomized  Control  Trial

Grana  et  al,  (2014)3

•  1549  total  par(cipants  (1189  of  which  were  current  smokers)  surveyed  at  baseline  and  follow  up  aber  one  year  

•  Survey  asked  (1)  history  of  EC  use  within  30  days,  (2)  number  of  cigareJes/day,  (3)  (me  to  first  cigareJe  (<30  vs  ≥  30  mins),  and  (4)  inten(on  to  quit  (never  vs  ≥  months  vs  ≤6  months  vs  ≤1  month)

•  EC  use  by  smokers  was  not  followed  by  either  smoking  abs(nence  or  reduc(on  in  cigareJe  consump(on  at  1-­‐year  follow  up

•  High  risk  of  selec(on  bias  as  they  did  not  validate  self-­‐reported  abs(nence  and  provide  a  clear  defini(on  of  abs(nence  

•  Only  88  of  the  949  smokers  reported  using  EC,  thus  lowering  the  sta(s(cal  power  to  detect  a  rela(onship  between  EC  and  smoking  cessa(on

Cohort  study

Polosa  et  al,  (2014)4

•  40  smokers  with  no  inten(on  of  quifng  within  30  days  

•  24-­‐weeks  of  interven(on  with  EC  •  Par(cipants  allowed  maximum  of  

4  cartridges/day  and  received  supplies  of  nico(ne  cartridges  at  weeks  4,  8,  and  12,  for  eCO  measurements  

•  Follow  up  conducted  at  18  and  24  months  following  interven(on  to  address  smoking  habits,  cigareJes/day,  exhaled  CO  measurements,  adverse  events  and  EC  use

•  80%  reduc(on  in  median  cigareJe  usage  from  25  to  4  by  the  end  of  the  study  (p<0.001)  

•  Overall  quit  rate  of  12.5  %    •  Combined  50%  sustained  

reduc(on  and  smoking  cessa(on  in  40%  by  study  end  (p<0.001)  

•  Typical  nico(ne  withdrawal  symptoms  appeared  mi(gated  by  EC  usage    

•  Levels  of  carbon  monoxide  detected  in  par(cipants  was  significantly  decreased  by  study  end  

•  Selec(on  bias  and  performance  bias  

•  Recall  bias  of  withdrawal  symptoms,  42.5%  of  par(cipants  failed  to  aJend  final  appointment    

Cohort  study