Globally, tobacco smoking is one of the leading causes of preventable death. Nearly one-fifth of adults in the UK regularly smoke cigarettes. Although this number is on the decline, costs of smoking to the NHS are upwards of £3 billion every year. Given the well documented health-risks many people are motivated to quit, but find it difficult to maintain abstinence (Ferguson et al, 2005). Without smoking cessation aids, it is estimated between only 2-5% of quit attempts are successful.

A number of active treatments exist to aid smoking cessation, broadly categorised into those that prompt quit attempts and those designed to assist with quitting. Treatments that assist with quitting range from Nicotine Replacement Therapy (NRT) to prescribed drugs such as varenicline and cytisine (the elf team have explored the effectiveness and side effects of smoking cessation treatments in previous blogs (Fluharty, 2014; Jones, 2014; Jones and Christiansen, 2013)). Both varenicline and cytisine are nicotinic receptor partial agonists, and are thought to act through relieving craving and withdrawal symptoms, whilst blocking the reinforcing effects of nicotine.

To date there have been no trials comparing the clinical effectiveness of varenicline to cytisine, therefore it is unknown which of the two drugs (if any) have greater clinical efficacy. Furthermore, although cytisine is reportedly cheaper, it is unclear whether it is more cost-effective.

A recent systematic review and economic evaluation published in Health Technology Assessment set out to examine the clinical effectiveness and safety of varenicline compared to cytisine for smoking cessation and to use an economic model to investigate the cost-effectiveness of both drugs (Leaviss et al, 2014).

Methods

The authors updated a search from a recent Cochrane review (Cahill et al, 2012) of 20 studies evaluating the clinical effectiveness of both cytisine and varenicline. Their search identified a further three studies. To be eligible studies had to be a randomised controlled trial examining adult smokers, including a comparison of cytisine or varenicline with either NRT, placebo or bupropion within a minimum abstinence follow up of 6 months.

Abstinence data was synthesised using a network meta-analysis. The analysis combined evidence across studies in which there was at least one treatment in a study that was common to at least one other study.

The cost-effectiveness analysis used the Benefits of Smoking Cessation on Outcomes (BENESCO) model, which has been used in a number of previous studies. The authors evaluated the cost-effectiveness of cytisine compared with varenicline, assuming standard doses of both drugs. The model used parameters from numerous sources and included the costs and outcomes associated with coronary heart disease, chronic obstructive pulmonary disease, lung cancer and other possible events associated with smoking. Individuals in the cohort were assumed to make a single, drug assisted quit attempt.

Treatment costs for cytisine were just £16.79, compared with £163.80 for varenicline. Cost-effectiveness was estimated from the perspective of the UK NHS, with life years and quality-adjusted life years (QALYs) as outcomes.

Results

Overall, the studies comprised of 10,610 participants, with the majority (21 of the 23 included studies) evaluating varenicline.

Of the identified interventions:

• Cytisine 1.5 mg six times daily, gradually lowered, produced the largest effect on continuous abstinence (HR 4.27, 95% CI 2.05 to 10.05) relative to placebo
• Cytisine was the intervention with highest probability of being most effective (p=0.87)
• Varenicline doses of 0.5 mg (HR 2.16, 95% CI 1.54 to 3.38) and 1.0 mg (HR 2.58, 95% CI 2.16 to 3.15) administered twice per day were also effective for abstinence, relative to placebo
• Varenicline doses of 0.3 mg (HR 1.58, 95% CI 0.65 to 3.53) and 1.0 mg (HR 1.08, 95% CI 0.40 to 2.63) once per day were not effective compared to placebo

In terms of side effects:

• Varenicline treatment was associated with significantly higher rates of headaches, insomnia and nausea compared to placebo
• Cytisine did not significantly differ compared to placebo on rates of headaches and nausea, and no data was available for insomnia

The total costs incurred in the two groups (over a lifetime horizon) were:

• £4,973 for cytisine
• £5,225 for varenicline
• Giving an incremental cost saving of £251 for cytisine

Incremental life years and QALYs were 0.03, resulting in a cost per QALY of around £8,500. Probabilistic sensitivity analysis identified that, at a willingness to pay of £20,000 per QALY, the probability that cytisine was cost-effective was over 90%.

The authors also carried out a value of information analysis, which is a framework used to estimate the value of future research. Perfect information about the hazard ratio of cytisine compared with varenicline, which could be garnered from a head-to-head trial, was valued at over £33 million. The authors estimate the most cost-effective course of action to be a trial with around 1,000 participants per arm.

Discussion

On the basis of the evidence in this review, varenicline and cytisine are both effective interventions for smoking cessation, compared with placebo.

Cytisine was estimated to be more clinically and economically cost effective, however given the assumptions of the economic model (in particular that an individual only makes a single quit attempt in their lifetime) we can’t make firm conclusions about the size of the potential cost savings associated with cytisine.

The most valuable output of the model in this case is the assertion that a large RCT of varenicline versus cytisine is highly likely to be cost-effective, and therefore recommended.

Links

Leaviss J, Sullivan W, Ren S, Everson-Hock E, Stevenson M, Stevens JW, et al. What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation. Health Technol Assess 2014;18(33).

Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews 2012, Issue 4 Art. No .: CD006103. DOI: 10.1002 / 14651858.CD006103.pub6.

Ferguson J, Bauld L, Chersterman J, Judge K. (2005). The English smoking treatment services: one-year outcomes. Addiction, 100, 59-69. [PubMed abstract]

Fluharty M. Varenicline, smoking cessation and neuropsychiatric adverse events. The Mental Elf, 9 Jan 2014.

Jones A. Do smoking cessation treatments increase the risk of depression and suicide? The Mental Elf, 13 Jan 2014.

Jones A, Christiansen P. New Cochrane review finds that NRT, bupropion and varenicline are effective treatments for smoking cessation. The Mental Elf, 31 May 2013.