Varenicline for "Gradual" vs. "Abrupt" Smoking Cessation in Low-motivated COPD Smokers: A Randomized Pilot Study

RATIONALE

Chronic obstructive lung disease (COPD) is an inflammatory disease characterized by progressive airflow limitation that is not fully reversible by the use bronchodilators .Cigarette smoking is the single most common cause of COPD . It is estimated that 15-20% of smokers will develop COPD over their lifetime, but higher figures have been reported for older smokers. Incidentally, previous studies showed that up to 20% of "healthy" smokers participating in cessation trials might have airway obstruction, most of whom are unaware of this diagnosis . There is no single explanation for the fact that only a fraction of smokers develop COPD. Bronchodilator treatment improves symptoms and quality of life of COPD patients, and new drugs are available for this purpose. Notwithstanding, smoking cessation remains the only therapeutic intervention likely to slow down the progression of the disease by preventing further decline of maximal expiratory flows . Thus, smoking cessation is paramount in the treatment of patients with COPD.

Although they know smoking is the cause of their disease, many patients with COPD continue to smoke. Smoking prevalence rates up to 80 % have been documented in patients with mild to moderate disease and up to 50% in those with severe disease . Notwithstanding, for various reasons COPD patients are more resistant to smoking cessation than "healthy" smokers; these include higher pack-year history and stronger nicotine dependence . In addition, COPD smokers are less motivated to quit and often suffer from depression, a known cause of failure in quit attempts . These observations call for new cessation strategies likely to prompt COPD smokers to attempt to quit smoking.

The standard way to stop smoking is to quit abruptly on a designated quit-day. However, for COPD patients, this can be very hard to achieve since, for them, smoking is not only a source of pleasure but also a longstanding habit, a second nature . An alternative strategy is the so-called "reduce-to-quit" or "gradual" cessation method. Although it also has a quit-day, the key difference is that smokers reduce the number of cigarettes/day over several days or weeks prior to quitting. To help smokers achieve and maintain reduction, pharmacotherapy is usually offered and, in many countries, nicotine replacement therapy (NRT) is licensed for this purpose.

Surprisingly enough, no studies have been published on the efficiency of varenicline as an aid for pre-quitting smoking reduction. Indeed, varenicline was found superior to any single type of NRT (and bupropion) as an aid for smoking cessation in adult smokers. . Second, it was found to be more efficient than placebo and NRT for "abrupt" cessation in COPD smokers motivated to quit ]. Finally, varenicline was found to decrease pre-quit enjoyment in general smokers and increase motivation to quit among healthy smokers who are not willing to make a serious attempt to quit smoking .