Nicotine e-cigarettes, varenicline, and cytisine most effective for long-term smoking cessation, analysis finds

Reviewed by Lily Ramsey, LLMSep 28 2023

A comprehensive new analysis has found that nicotine e-cigarettes, varenicline and cytisine are the most effective options currently available for helping smokers quit long-term (going at least six months without smoking). This is closely followed by using two forms of nicotine replacement therapy at the same time, such as a nicotine patch alongside gum, lozenges, or nasal sprays. The research was conducted by a team from the Nuffield Department of Primary Care Health Sciences at the University of Oxford with colleagues from the University of Leicester.

The study, published in the Cochrane Database of Systematic Reviews, compared the results for different stop-smoking aids that have been used in over 300 clinical trials involving more than 150,000 people. The researchers used a statistical technique to combine data from the studies into a single analysis called "component network meta-analysis" (CNMA). This meant they could compare smoking cessation methods against each other, using both direct comparisons within trials and indirect comparisons across trials. This provided a comprehensive view of the relative effectiveness of each method.

Dr Nicola Lindson, lead author and a Senior Researcher and Lecturer based within Oxford's Nuffield Department of Primary Care Health Sciences, emphasised the potential impact of the findings:
"Our research dives deep into the world of smoking cessation. By pulling together data from hundreds of studies and over 150,000 people, we can see that when people use the medicines licenced for quitting smoking or nicotine e-cigarettes, they are more likely to quit than if they do not use these aids. We have also shown that nicotine e-cigarettes, cytisine, and varenicline appear to help more people quit than other products used to stop smoking. Nicotine replacement therapy appears to be almost as effective, but only when a patch is used alongside another form of nicotine replacement, such as gum or nasal spray."

E-cigarettes were found to help around 14 smokers per 100 quit long-term, compared to 6 in 100 trying to quit without any of the stop-smoking aids studied. The smoking cessation medicines varenicline and cytisine were similarly effective. However, varenicline, a WHO essential medicine, is not currently available in Europe, South America, Japan, and parts of North America due to a manufacturing problem. Cytisine is not currently licensed or marketed in most countries outside of central and Eastern Europe, meaning it is unavailable in most of the world, including the UK and US. This leaves nicotine e-cigarettes and combination nicotine replacement therapies as the two most effective stop-smoking aids available to most people. These work better when people are also receiving behavioral support to quit.

Using two types of nicotine replacement therapy (NRT) together, such as a nicotine patch plus a faster-acting NRT product like gum or lozenges, may be almost as effective as nicotine e-cigarettes, varenicline and cytisine. However, using a single form of NRT, like the patch or gum alone, resulted in fewer additional quitters. The review estimates that around 12 in 100 people using two forms of NRT together will quit successfully, compared to around 9 in 100 people using only one type. The estimate for combined NRT is less certain than those for other stop-smoking aids, as it was calculated from the combined effects of individual NRTs rather than directly from trials of combination therapies.

Smoking is a significant health concern and cause of death worldwide. However, it is very difficult to quit. There are several products available to help with this, but the relative effectiveness of these methods has long been uncertain. This comprehensive analysis now offers clarity, providing people who smoke, healthcare professionals, and policymakers with reliable data to make informed decisions.
The researchers incorporated key factors like the effectiveness of various interventions and their safety profiles. The study's findings could be vital information to help reshape public health policies and strategies, offering smokers more effective tools to quit for good.

Dr Jamie Hartmann-Boyce, co-author who was based at the University of Oxford during the research and is now Assistant Professor at the University of Massachusetts Amherst, said:
"In sifting through extensive data, we've gained valuable insights into effective smoking cessation methods. Smoking remains the leading cause of preventable disease and death worldwide, and though many people want to quit smoking, it can be hard to do so. Our findings provide clear evidence of the effectiveness of nicotine e-cigarettes and combination nicotine replacement therapies to help people quit smoking. The evidence also is clear on the benefits of medicines cytisine and varenicline, but these may be harder for some people to access at the moment. The best thing someone who smokes can do for their health is to quit smoking, and evidence shows that using varenicline, cytisine, or nicotine e-cigarettes in combination with behavioral support will give them the best chances of successfully doing so."

The review focused exclusively on evaluating the efficacy of a range of smoking cessation methods, aligning with its defined scope and primary research focus. It did not delve into broader aspects of the public health discourse regarding e-cigarettes, such as their usage among non-smokers and adolescents. While the review uncovered no substantial evidence of significant adverse effects, it is important to note that most studies tracked participants for a period ranging from six to twelve months, leaving a gap in data concerning potential long-term consequences.

The massive study concluded that more data on serious side effects and the number of people who stop using a product due to side effects would be beneficial. However, this robust analysis provides strong evidence to inform treatment guidelines and policies aimed at helping smokers quit.