Is combined NRT therapy the best bet for smoking cessation?


Groundbreaking new research has found that current smokers are three times more likely to die from cardiovascular disease (CVD), but these risks greatly decrease among those who quit. Combining fast-acting nicotine replacement therapy (NRT) can have a big impact on the likelihood of cessation.

The Australian study comprised 188,167 participants aged 45 and above who did not have CVD or cancer, in a linked questionnaire with 267,153 people aged 45 and over.

Of the participants, 8% were current and 34% were past smokers. Event rates for 29 out of the 36 most common CVD subtypes were significantly increased in current smokers.1

Helping smokers quit

A Cochrane Systematic Review found that combining a fast-acting NRT such as gum or lozenge with a patch has higher long-term quit rates for smokers than any single form of NRT.2

There was also high-certainty evidence that 4 mg versus 2 mg nicotine gum increases the chances of successfully quitting after six months, according to the review of randomised controlled trials, cluster-randomised and quasi-randomised trials involving the use of NRT.

The review identified 63 trials with 41,509 participants, mostly adults, recruited from the community or healthcare clinics across the United States (39 studies), Europe (14), Australasia (4), South Africa (2) and South America, Canada, China and multiple regions (1 each). Participants typically smoked at least 15 cigarettes daily and were motivated to quit.2

NRT is available as skin patches, mouth sprays, inhalators, gum and lozenges. It is formulated for absorption through oral or nasal mucosa or skin and is recommended by multiple clinical guidelines as a first-line treatment to break the psychological and physiological dependence on smoking which is one of the leading causes of preventable disease in Australia.

The review’s comparison of nicotine patch doses found that higher quit rates were more likely if people used higher dose nicotine patches. Patches of 25 mg (worn over 16 hours) were compared to 15mg (worn over 16 hours), and 21 mg patches (worn over 24 hours) were compared to or 14 mg patches (worn over 24 hours). However, the evidence for these findings was of moderate certainty due to imprecision in the results (low numbers). The review found no evidence of an effect on duration of nicotine patch use (16 hours versus 24 hours daily).2

High-certainty evidence suggested that fast-acting NRT such as lozenges or gum resulted in similar quit rates to nicotine patches when used as a single treatment.

While there is ‘moderate-certainty evidence’ that using NRT prior to quit day – instead of from the day of cessation – may improve quit rates, further research is needed to establish this finding, the authors concluded.2

Most comparisons found no evidence of serious adverse effects, although the evidence for the comparative safety and tolerability of different types of NRT use was of low certainty. The authors recommended that cardiac adverse events and serious adverse events, and withdrawals from trials due to treatment, should be  measured and reported in any new studies.2 

There is clear evidence that NRT used after smoking cessation is effective, but this review aimed to determine whether different forms, deliveries, doses, durations of treatment, or use before cessation, improved its efficacy in achieving long-term smoking cessation.

However the authors did acknowledge limitations of this systematic review, as mentioned earlier, and implications that further research is needed. More high quality studies are needed to compare high versus low-dose patches, different durations of therapy, different types of fast-acting NRT, and NRT pre-loading versus standard use.2

Pharmacist involvement

The rate of smoking cessation in Australia has slowed over the last few years, most likely due to a decrease in public education campaigns to motivate people. 

Pharmacists are seen as an authoritative but underutilised asset in smoking cessation. They can provide advice on proven methods such as outlined in this review.

Pharmacist and Mayo Clinic Certified Tobacco Treatment Specialist Lyn Baucia said that in most cases, depending on the level of dependence, pharmacists should always recommend high dose patches and faster acting gum and lozenges as this results in higher quit rates. 

She said that evidence points the effectiveness of 4 mg gum, which can result in 12% to 83% higher quit rates than 2 mg gum, and that a pre-cessation nicotine patch (preloading) can increase the effect by 34%.

‘Reducing to quit, where NRT is used to reduce the number of cigarettes smoked before stopping completely has also been shown to assist smokers, especially those not willing to quit.’

Ms Baucia said that pharmacists are perfectly placed to address smoking cessation with their patients, and that there are many opportunities where pharmacists can ask patients about their smoking, offer education and provide support.

‘It is highly recommended that smokers that identify as dependent are encouraged to use Combination NRT Therapy. Pharmacists should give detailed information about the different products, their use  and methods of quitting. Follow up support should be a part of our clinical practice.

‘Awareness that the phrase “quit smoking” has negative connotations for many smokers and referring to it  as “managing smoking” can in many cases make this unsurmountable goal achievable,’ she said.


  1. Banks E, Joshy G, Rosemary J. Korda RJ, Stavreski B, Soga K, Egger S, Day C, Clarke NE, Lewington S, Lopez AD. Tobacco smoking and risk of 36 cardiovascular disease subtypes: fatal and non-fatal outcomes in a large prospective Australian study. BMC Medicine 2019. At:
  2. Lindson L, Chepkin SC, Ye W, Fanshawe TR, Bullen C, Hartmann-Boyce J. Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation. Cochrane Systematic Review, April 2019. At: