Evidence update: What’s best?
Since 2009, many clinical trials have examined the best way to help smokers quit. Here’s a closer look at the latest evidence.
NRT boosts long-term cessation
A 2012 Cochrane review examined 150 trials and found that every type of NRT—gum, lozenge, patch, inhaler, and nasal spray—was associated with long-term cessation (relative risk [RR], 1.60).8 This effect was essentially unchanged regardless of the duration, setting, or intensity of supportive therapy offered, and no single type of NRT was more effective than any other. However, combining a short-acting form, such as a lozenge, with a long-acting patch was found to be more effective than either one alone (RR, 1.34).
Starting the NRT before the patient quit did not improve cessation rates over traditional start times (RR, 1.18). Neither was there an added benefit to using NRT beyond the recommended 24-week prescription period,9 although doing so was found to be safe. Another 2012 Cochrane review looked specifically at the use of pharmacologic smoking cessation interventions during pregnancy and concluded that there was still not sufficient data to document efficacy for this patient population.10
Adherence. In deciding on which type of NRT to prescribe, it is important to consider not only patient preference and previous efforts but also the latest evidence. A study comparing various NRT formulations found patient adherence to be highest with the patch, followed by nicotine gum, which had a higher compliance rate than either the nicotine inhaler or nasal spray.11
Varenicline is still a firstline agent
Since the 2008 guideline recommended this partial nicotinic receptor agonist/antagonist as a firstline pharmacologic agent, additional meta-analyses have confirmed its long-term efficacy in smokers who are ready to quit.12,13 A 2012 Cochrane review found varenicline to increase long-term cessation compared with placebo (RR, 2.27).13 It also showed varenicline to be more effective than bupropion SR (RR, 1.52), but about as effective as NRT (RR, 1.13).
Newer data suggest that varenicline may also be effective for those who are willing to cut down on smoking but not yet ready to give up cigarettes completely. Used for 24 weeks by those who were initially resistant to quitting, researchers found varenicline nearly tripled the cessation rate at 52 weeks compared with placebo (RR, 2.7).14
Latest evidence on safety. Additional concerns about the safety of varenicline have been raised, however, since the 2008 guideline was published. In 2009, the FDA required that black box warnings be added to the labels of both varenicline and bupropion SR based on postmarketing safety reports showing risk for neuropsychiatric symptoms, including suicidality.15 In 2011, a large case-control study by the FDA Adverse Event Reporting System also showed an increased risk for suicidality in patients taking these drugs.16
Follow-up studies, however, including a large prospective cohort study and a large meta-analysis, failed to show an increased association with neuropsychiatric adverse effects.17,18 A smaller randomized controlled trial (RCT) showed that in smokers diagnosed with schizophrenia and bipolar disorder, maintenance therapy with varenicline was effective in preventing smoking relapse for up to 52 weeks. Abstinence rates were 60% for those in the varenicline group versus 19% for those in the placebo group (OR, 6.2). Although no increased risk for adverse psychiatric events was found in this study, it was not powered to detect them.19 Also of note: A meta-analysis of 14 RCTs showed an increased rate of cardiovascular events associated with varenicline.20 There are concerns about methodologic flaws in this meta-analysis, however, and two subsequent meta-analyses failed to find a cardiovascular risk.21,22
The higher quality studies that have been published since the original concerns about varenicline’s safety are reassuring, but it is still essential to carefully weigh the risks and benefits of varenicline. Review cardiac and psychiatric history and conduct a suicidality assessment before prescribing it as a smoking cessation aid, and provide close follow-up.
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