After breaking down the evidence which reiterates the importance of smoking cessation after a cardiovascular event (Part 1 and Part 2), hopefully, there needs no further convincing on following through with the subsequent steps of quitting.
Appropriate introduction and pharmacotherapy management for smoking cessation have demonstrated efficacy as illustrated in the tables below. However, it is imperative to understand that only a combination of both medical management and behavioural support will yield greater success than either used alone. Of which the latter will be covered in the next article.
With that, let’s delve into the first-line agents for smoking cessation.
Nicotine Replacement Therapies
Nicotine, with its highly addictive properties, is possibly the greatest barrier to overcoming the initial challenge of smoking cessation. Nicotine replacement therapies, essentially provide a means for the gradual weaning of nicotine, while eliminating tobacco use entirely to diminish the noxious health consequences of the latter.
Nicotine replacement therapies now come in multiple dosage forms, with the most significant difference being their length of duration. The other differences are subtle but provide different options for the patient depending on their needs and preferences.
| Agent | Nicotine Patch | Nicotine Chewing Gum | Nicotine Lozenge | Nicotine Mouth Spray |
| How it helps | Slow-rising plasma nicotine level (1-2H), reduces the inhaled nicotine bolus effect of smoking (10s) believed to contribute to its addictive potential; also continuously manages withdrawal symptoms. | Largely controls cue-induced cravings that come with situational stimuli and behavioural/sensory aspects of smoking e.g. something in the mouth, or between fingers, with fast relief from withdrawal symptoms. | ||
| Dosage to be individualised based on patient’s dependency on cigarettes e.g. how many sticks a day and how soon after waking does one smoke his / her first cigarette | ||||
| Efficacy | Cochrane review of 132 trials concluded that all forms of NRTs increased the chance of quitting successfully by 50-60%1. The consensus amongst experts, with meta-analysis of 9 randomised trials, suggests combining long-acting patches w/ short-acting NRT for greater efficacy. | |||
| Advantages | Suitable for heavy, habitual smokers. | May delay weight gain, helps with oral gratification | ||
| Discrete, easy to use | The additional behavioural aspect of holding something in their hands; more rapid nicotine absorption, resulting in quicker satisfaction of cravings compared to gum/lozenge2. | |||
| Side-Effects | Depression, dizziness, headache, insomnia, lack of concentration, nervousness, pain, paraesthesia, GI distress | |||
| Vivid dreams sleep disturbances, rash | Dysgeusia increased salivation, jaw ache | Dysgeusia, xerostomia, throat irritation, hiccups | Hiccups, throat irritation, nausea | |
| Counselling |
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Avoid coffee, juices, and fizzy drinks 15 minutes before use (lowered pH can reduce the absorption of nicotine) | ||
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Other options:
| Agent | Bupropion SR | Varenicline |
| How it helps | Dopamine/NE reuptake inhibitor (relatively weak) | Selective nicotinic receptor agonist acts on the α4β42 nicotinic cholinergic receptor that is most important for addiction, with a lower affinity for the α3β4 receptor, which mediates cardiovascular effects. |
| Dosage | Initiate x1/2-52 before quit date:
150mg OM x3/7THEN 150mg BD Longer-duration therapy (up to a year) may prevent relapse in successful quitters. |
Initiate x1/2-52 before the quit date: Day 1-3: 0.5mg OD Day 4-7: 0.5mg BD THEN 1mg BD for a recommended total duration of 12 weeks.May consider extended maintenance therapy based on individual patient’s risk-benefit.Quit date can be set up to 35 days after initiation; alternatively aim to reduce smoking by 50% every 4 weeks, with complete cessation at 12 weeks. Relapse may be prevented by continuing varenicline for another 12 weeks after cessation. Requires renal impairment for CrCl < 30ml/min |
| Efficacy | Cochrane review of 19 randomised trials showed double the odds of smoking cessation vs placebo. | Specifically indicated for smoking cessation; with higher rates of abstinence when compared to bupropion and NRT3; and 2-3 fold higher quit rates vs placebo. |
| Advantages | Consider patients with a past medical history of depression, delays weight gain; can be combined w/ NRT | Effective even when employed as monotherapy without NRT4; suggested in patients with psychiatric illness |
| Side-Effects | Insomnia, headache, diaphoresis, xerostomia, tachycardia
Contraindications: history of seizures, bipolar disorder, anorexia/bulimia, MAOI use in the past 14 days |
> 10%: Headache, insomnia, vivid dreams, nausea, vomiting, depressed moods, irritability
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| Counselling |
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Q: Does it matter when I quit?
The RESPONSE trial5 conducted with 324 smokers post-ACS in the Netherlands, showed that the majority of successful quitters (n=156) quit immediately (82%, n=128) after the event and remained abstinent through a year of follow-up, without extra support, compared to the remaining who did not attempt (n=152), or had a late attempt at quitting (n=44) but relapsed (36%, n=16).
Q: Is it safe to start pharmacotherapy for smoking cessation immediately post-MI?
In general, guidelines e.g. AAFP, have stated that NRTs be used with caution in the immediate (2-week) post-MI period, or in patients with serious or worsening angina pectoris. This stems from their inherent adrenergic and vasoconstrictive properties and lack of clear guidance from evidence.
A network meta-analysis7 through 10 electronic databases involving 63 RCTs of the 3 main treatment modalities (21 nicotine, 28 bupropion, 18 varenicline) showed no increase in the risk of all composite CV disease events with bupropion (relative risk [RR], 0.98; 95% confidence interval [CI], 0.54-1.73) or varenicline (RR, 1.30; 95% CI, 0.79-2.23).
There was an elevated risk associated with nicotine replacement therapy that was driven predominantly by less serious events e.g. tachycardia and palpitations (RR, 2.29; 95% CI, 1.39-3.82). However, one must take into consideration that the comparators were patients on a placebo.
When studies compared patients who continued smoking and those on nicotine patches, there was an equivalence of palpitations or chest pain between both groups, attributable to the coronary vasoconstrictive effects of nicotine.
When we examined MACE, we found a protective effect with bupropion (RR, 0.45; 95% CI, 0.21-0.85) [antidepressant origins may result in a possible reduction in vascular stress, apart from alleviating depression that may come from a life-threatening event] and no clear evidence of harm with varenicline (RR, 1.34; 95% CI, 0.66-2.66) or nicotine replacement therapy (RR, 1.95; 95% CI, 0.26-4.30).
Ultimately, cautious initiation can be initiated in whom the benefits appear to outweigh the risks.
Q: How about quitting normal cigarettes by using e-cigarettes instead?
Albeit offering reduced toxicant exposure and fewer short-term respiratory symptoms compared to traditional cigarettes, these novel nicotine delivery devices are not yet well-evaluated, with their components and long-term health effects left largely unknown. Hence, e-cigarettes are still not considered cessation devices.
References
- Hartmann-Boyce J, Chepkin SC, Ye W, Bullen C, Lancaster T. Nicotine replacement therapy versus control for smoking cessation. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No.: CD000146. DOI: 10.1002/14651858.CD000146.pub5
- Tønnesen P, Lauri H, Perfekt R, Mann K, Batra A. Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial. Eur Respir J. 2012 Sep;40(3):548-54. doi: 10.1183/09031936.00155811. Epub 2012 Feb 9. PMID: 22323576; PMCID: PMC3432241.
- Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;387(10037):2507-20.
- Baker TB, Piper ME, Smith SS, Bolt DM, Stein JH, Fiore MC. Effects of Combined Varenicline With Nicotine Patch and of Extended Treatment Duration on Smoking Cessation: A Randomized Clinical Trial. JAMA. 2021 Oct 19;326(15):1485-1493. doi: 10.1001/jama.2021.15333. PMID: 34665204; PMCID: PMC8527361.
- Snaterse M, Scholte Op Reimer WJ, Dobber J, et al. Smoking cessation after an acute coronary syndrome: immediate quitters are successful quitters. Neth Heart J. 2015;23(12):600–607. doi:10.1007/s12471-015-0755-9
- Neal L, Benowitz, Judith J, Prochaska. (2013) Smoking Cessation after Acute Myocardial Infarction. Journal of the American College of Cardiology. 61 (5) 533-535;DOI:10.1016/j.jacc.2012.11.017
- Mills EJ, Thorlund K, Eapen S, Wu P, Prochaska JJ. Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis. Circulation. 2014;129(1):28-41.
- Eisenberg MJ, Grandi SM, Gervais A, et al. Bupropion for smoking cessation in patients hospitalized with acute myocardial infarction: a randomized, placebo-controlled trial. J Am Coll Cardiol. 2013;61(5):524-32.
